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Biomarkery zánětlivého postižení subchondrální kosti při axiální spondyloartritidě.
Název práce v češtině: Biomarkery zánětlivého postižení subchondrální kosti při axiální spondyloartritidě.
Název v anglickém jazyce: Biomarkers of subchondral bone damage caused by inflammation in axial spondyloarthritis.
Klíčová slova: axiální spondyloartritida, ankylozující spondylitida, non-radiografická axiální spondylitida, degradační produkty metaloproteináz, adipokiny, microRNA, Hsp90, magnetická rezonance, kostní edém, syndesmofyt
Klíčová slova anglicky: axial spondyloarthritis, ankylosing spondylitis, non-radiographic axial spondyloarthritis, matrix metalloproteinase mediated metabolites, adipokines, microRNA, Hsp90, magnetic resonance, bone marrow edema, syndesmophyte
Akademický rok vypsání: 2014/2015
Typ práce: disertační práce
Jazyk práce: čeština
Ústav: Revmatologická klinika 1. LF UK a Revmatologický ústav (11-00641)
Vedoucí / školitel: prof. MUDr. Karel Pavelka, DrSc.
Řešitel: skrytý - zadáno a potvrzeno stud. odd.
Datum přihlášení: 07.10.2014
Datum zadání: 07.10.2014
Datum potvrzení stud. oddělením: 07.10.2014
Datum a čas obhajoby: 10.12.2020 11:30
Místo konání obhajoby: Fyziologický ústav 1 .LF UK, Albertov 5, 128 00, Praha 2
Datum odevzdání elektronické podoby:20.05.2020
Datum proběhlé obhajoby: 10.12.2020
Předmět: Obhajoba dizertační práce (B90002)
Oponenti: prof. MUDr. Pavel Horák, CSc.
  prof. MUDr. Zbyněk Hrnčíř, DrSc.
 
 
Konzultanti: prof. MUDr. Ladislav Šenolt, Ph.D.
Seznam odborné literatury
ALMODOVAR, R., RIOS, V., OCANA, S., GOBBO, M., CASAS, M. L., ZARCO-MONTEJO, P. & JUANOLA, X. 2014. Association of biomarkers of inflammation, cartilage and bone turnover with gender, disease activity, radiological damage and sacroiliitis by magnetic resonance imaging in patients with early spondyloarthritis. Clin Rheumatol, 33, 237-41.
ALTHOFF, C. E., FEIST, E., BUROVA, E., ESHED, I., BOLLOW, M., HAMM, B. & HERMANN, K.-G. A. 2009. Magnetic resonance imaging of active sacroiliitis: Do we really need gadolinium? European Journal of Radiology, 71, 232-236.
ALVAREZ-NAVARRO, C. & LOPEZ DE CASTRO, J. A. 2014. ERAP1 structure, function and pathogenetic role in ankylosing spondylitis and other MHC-associated diseases. Mol Immunol, 57, 12-21.
ANTONELLI, M. J. & MAGREY, M. 2017. Sacroiliitis mimics: a case report and review of the literature. BMC Musculoskeletal Disorders, 18, 170.
ANTONIOU, A. N., LENART, I. & GUILIANO, D. B. 2011. Pathogenicity of Misfolded and Dimeric HLA-B27 Molecules. Int J Rheumatol, 2011, 486856.
APPEL, H., JANSSEN, L., LISTING, J., HEYDRICH, R., RUDWALEIT, M. & SIEPER, J. 2008. Serum levels of biomarkers of bone and cartilage destruction and new bone formation in different cohorts of patients with axial spondyloarthritis with and without tumor necrosis factor-alpha blocker treatment. Arthritis Res Ther, 10, R125.
APPEL, H., KUHNE, M., SPIEKERMANN, S., KOHLER, D., ZACHER, J., STEIN, H., SIEPER, J. & LODDENKEMPER, C. 2006a. Immunohistochemical analysis of hip arthritis in ankylosing spondylitis: evaluation of the bone-cartilage interface and subchondral bone marrow. Arthritis Rheum, 54, 1805-13.
APPEL, H., LODDENKEMPER, C., GROZDANOVIC, Z., EBHARDT, H., DREIMANN, M., HEMPFING, A., STEIN, H., METZ-STAVENHAGEN, P., RUDWALEIT, M. & SIEPER, J. 2006b. Correlation of histopathological findings and magnetic resonance imaging in the spine of patients with ankylosing spondylitis. Arthritis Res Ther, 8, R143.
APPEL, H., MAIER, R., WU, P., SCHEER, R., HEMPFING, A., KAYSER, R., THIEL, A., RADBRUCH, A., LODDENKEMPER, C. & SIEPER, J. 2011. Analysis of IL-17(+) cells in facet joints of patients with spondyloarthritis suggests that the innate immune pathway might be of greater relevance than the Th17-mediated adaptive immune response. Arthritis Res Ther, 13, R95.
APPEL, H., RUIZ-HEILAND, G., LISTING, J., ZWERINA, J., HERRMANN, M., MUELLER, R., HAIBEL, H., BARALIAKOS, X., HEMPFING, A., RUDWALEIT, M., SIEPER, J. & SCHETT, G. 2009. Altered skeletal expression of sclerostin and its link to radiographic progression in ankylosing spondylitis. Arthritis Rheum, 60, 3257-62.
BAEK, J. M., AHN, S. J., CHEON, Y. H., LEE, M. S., OH, J. & KIM, J. Y. 2017. Nicotinamide phosphoribosyltransferase inhibits receptor activator of nuclear factor-kappaB ligand-induced osteoclast differentiation in vitro. Mol Med Rep, 15, 784-792.
BAL, A., UNLU, E., BAHAR, G., AYDOG, E., EKSIOGLU, E. & YORGANCIOGLU, R. 2007. Comparison of serum IL-1 beta, sIL-2R, IL-6, and TNF-alpha levels with disease activity parameters in ankylosing spondylitis. Clin Rheumatol, 26, 211-5.
BARALIAKOS, X. 2015. The contribution of imaging in the diagnosis and treatment of axial spondyloarthritis. Eur J Clin Invest, 45, 81-6.
BARALIAKOS, X., BOEHM, H., SAMIR BARAKAT, A., SCHETT, G. & BRAUN, J. 2018. OP0242 Fatty lesions detected on mri scans in patients with ankylosing spondylitis are based on the deposition of fat in the vertebral bone marrow. Annals of the Rheumatic Diseases, 77, 170-170.
BARALIAKOS, X. & BRAUN, J. 2015. Non-radiographic axial spondyloarthritis and ankylosing spondylitis: what are the similarities and differences? RMD Open, 1.
BARALIAKOS, X., HELDMANN, F., CALLHOFF, J., LISTING, J., APPELBOOM, T., BRANDT, J., VAN DEN BOSCH, F., BREBAN, M., BURMESTER, G., DOUGADOS, M., EMERY, P., GASTON, H., GRUNKE, M., VAN DER HORST-BRUINSMA, I. E., LANDEWE, R., LEIRISALO-REPO, M., SIEPER, J., DE VLAM, K., PAPPAS, D., KILTZ, U., VAN DER HEIJDE, D. & BRAUN, J. 2014. Which spinal lesions are associated with new bone formation in patients with ankylosing spondylitis treated with anti-TNF agents? A long-term observational study using MRI and conventional radiography. Ann Rheum Dis, 73, 1819-25.
BARALIAKOS, X., LISTING, J., RUDWALEIT, M., HAIBEL, H., BRANDT, J., SIEPER, J. & BRAUN, J. 2007. Progression of radiographic damage in patients with ankylosing spondylitis: defining the central role of syndesmophytes. Ann Rheum Dis, 66, 910-5.
BARON, R. & KNEISSEL, M. 2013. WNT signaling in bone homeostasis and disease: from human mutations to treatments. Nat Med, 19, 179-92.
BASU, S., BINDER, R. J., SUTO, R., ANDERSON, K. M. & SRIVASTAVA, P. K. 2000. Necrotic but not apoptotic cell death releases heat shock proteins, which deliver a partial maturation signal to dendritic cells and activate the NF-kappa B pathway. Int Immunol, 12, 1539-46.
BAY-JENSEN, A. C., KARSDAL, M. A., VASSILIADIS, E., WICHUK, S., MARCHER-MIKKELSEN, K., LORIES, R., CHRISTIANSEN, C. & MAKSYMOWYCH, W. P. 2013a. Circulating citrullinated vimentin fragments reflect disease burden in ankylosing spondylitis and have prognostic capacity for radiographic progression. Arthritis Rheum, 65, 972-80.
BAY-JENSEN, A. C., LEEMING, D. J., KLEYER, A., VEIDAL, S. S., SCHETT, G. & KARSDAL, M. A. 2012. Ankylosing spondylitis is characterized by an increased turnover of several different metalloproteinase-derived collagen species: a cross-sectional study. Rheumatol Int, 32, 3565-72.
BAY-JENSEN, A. C., WICHUK, S., BYRJALSEN, I., LEEMING, D. J., MORENCY, N., CHRISTIANSEN, C., KARSDAL, M. A. & MAKSYMOWYCH, W. P. 2013b. Circulating Protein Fragments of Cartilage and Connective Tissue Degradation Are Diagnostic and Prognostic Markers of Rheumatoid Arthritis and Ankylosing Spondylitis. PLoS ONE, 8, e54504.
BELLAVIA, D., DE LUCA, A., CARINA, V., COSTA, V., RAIMONDI, L., SALAMANNA, F., ALESSANDRO, R., FINI, M. & GIAVARESI, G. 2019. Deregulated miRNAs in bone health: Epigenetic roles in osteoporosis. Bone, 122, 52-75.
BEN RADHIA, K., AYED-JENDOUBI, S., SFAR, I., BEN ROMDHANE, T., MAKHLOUF, M., GORGI, Y. & AYED, K. 2008. Distribution of HLA-B*27 subtypes in Tunisians and their association with ankylosing spondylitis. Joint Bone Spine, 75, 172-5.
BENHAMOU, M., GOSSEC, L. & DOUGADOS, M. 2010. Clinical relevance of C-reactive protein in ankylosing spondylitis and evaluation of the NSAIDs/coxibs' treatment effect on C-reactive protein. Rheumatology (Oxford), 49, 536-41.
BENJAMIN, M. & MCGONAGLE, D. 2009. The enthesis organ concept and its relevance to the spondyloarthropathies. Adv Exp Med Biol, 649, 57-70.
BIOMARKERS DEFINITION GORKING GROUP. 2001. Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther, 69, 89-95.
BOKAREWA, M., NAGAEV, I., DAHLBERG, L., SMITH, U. & TARKOWSKI, A. 2005. Resistin, an Adipokine with Potent Proinflammatory Properties. The Journal of Immunology, 174, 5789-5795.
BOLLOW, M., FISCHER, T., REISSHAUER, H., BACKHAUS, M., SIEPER, J., HAMM, B. & BRAUN, J. 2000. Quantitative analyses of sacroiliac biopsies in spondyloarthropathies: T cells and macrophages predominate in early and active sacroiliitis- cellularity correlates with the degree of enhancement detected by magnetic resonance imaging. Ann Rheum Dis, 59, 135-40.
BOLLOW, M., HERMANN, K. G., BIEDERMANN, T., SIEPER, J., SCHONTUBE, M. & BRAUN, J. 2005. Very early spondyloarthritis: where the inflammation in the sacroiliac joints starts. Ann Rheum Dis, 64, 1644-6.
BORNMAN, L., POLLA, B. S. & GERICKE, G. S. 1996. Heat-shock protein 90 and ubiquitin: developmental regulation during myogenesis. Muscle Nerve, 19, 574-80.
BRAUN, J., BOLLOW, M., NEURE, L., SEIPELT, E., SEYREKBASAN, F., HERBST, H., EGGENS, U., DISTLER, A. & SIEPER, J. 1995. Use of immunohistologic and in situ hybridization techniques in the examination of sacroiliac joint biopsy specimens from patients with ankylosing spondylitis. Arthritis Rheum, 38, 499-505.
BRAUN, J., BOLLOW, M., REMLINGER, G., EGGENS, U., RUDWALEIT, M., DISTLER, A. & SIEPER, J. 1998a. Prevalence of spondylarthropathies in HLA-B27 positive and negative blood donors. Arthritis Rheum, 41, 58-67.
BRAUN, J., BOLLOW, M. & SIEPER, J. 1998b. Radiologic diagnosis and pathology of the spondyloarthropathies. Rheum Dis Clin North Am, 24, 697-735.
BREBAN, M. 1998. Genetic studies of spondylarthropathies. French Spondylarthropathy Genetic Study Group. Ann Med Interne (Paris), 149, 142-4.
CALIN, A., PORTA, J., FRIES, J. F. & SCHURMAN, D. J. 1977. Clinical history as a screening test for ankylosing spondylitis. Jama, 237, 2613-4.
CARTER, N., WILLIAMSON, L., KENNEDY, L. G., BROWN, M. A. & WORDSWORTH, B. P. 2000. Susceptibility to ankylosing spondylitis. Rheumatology (Oxford), 39, 445.
CICCIA, F., GUGGINO, G., RIZZO, A., ALESSANDRO, R., LUCHETTI, M. M., MILLING, S., SAIEVA, L., CYPERS, H., STAMPONE, T., DI BENEDETTO, P., GABRIELLI, A., FASANO, A., ELEWAUT, D. & TRIOLO, G. 2017. Dysbiosis and zonulin upregulation alter gut epithelial and vascular barriers in patients with ankylosing spondylitis. Ann Rheum Dis, 76, 1123-1132.
CICCIA, F., GUGGINO, G., RIZZO, A., SAIEVA, L., PERALTA, S., GIARDINA, A., CANNIZZARO, A., SIRECI, G., DE LEO, G., ALESSANDRO, R. & TRIOLO, G. 2015. Type 3 innate lymphoid cells producing IL-17 and IL-22 are expanded in the gut, in the peripheral blood, synovial fluid and bone marrow of patients with ankylosing spondylitis. Ann Rheum Dis, 74, 1739-47.
COEN, G. 2004. Leptin and bone metabolism. J Nephrol, 17, 187-9.
COLBERT, R. A., TRAN, T. M. & LAYH-SCHMITT, G. 2014. HLA-B27 misfolding and ankylosing spondylitis. Mol Immunol, 57, 44-51.
COLLINS, E. J., GARBOCZI, D. N. & WILEY, D. C. 1994. Three-dimensional structure of a peptide extending from one end of a class I MHC binding site. Nature, 371, 626-9.
CORTES, A., HADLER, J., POINTON, J. P., ROBINSON, P. C., KARADERI, T., LEO, P., CREMIN, K., PRYCE, K., HARRIS, J., LEE, S., JOO, K. B., SHIM, S. C., WEISMAN, M., WARD, M., ZHOU, X., GARCHON, H. J., CHIOCCHIA, G., NOSSENT, J., LIE, B. A., FORRE, O., TUOMILEHTO, J., LAIHO, K., JIANG, L., LIU, Y., WU, X., BRADBURY, L. A., ELEWAUT, D., BURGOS-VARGAS, R., STEBBINGS, S., APPLETON, L., FARRAH, C., LAU, J., KENNA, T. J., HAROON, N., FERREIRA, M. A., YANG, J., MULERO, J., FERNANDEZ-SUEIRO, J. L., GONZALEZ-GAY, M. A., LOPEZ-LARREA, C., DELOUKAS, P., DONNELLY, P., BOWNESS, P., GAFNEY, K., GASTON, H., GLADMAN, D. D., RAHMAN, P., MAKSYMOWYCH, W. P., XU, H., CRUSIUS, J. B., VAN DER HORST-BRUINSMA, I. E., CHOU, C. T., VALLE-ONATE, R., ROMERO-SANCHEZ, C., HANSEN, I. M., PIMENTEL-SANTOS, F. M., INMAN, R. D., VIDEM, V., MARTIN, J., BREBAN, M., REVEILLE, J. D., EVANS, D. M., KIM, T. H., WORDSWORTH, B. P. & BROWN, M. A. 2013. Identification of multiple risk variants for ankylosing spondylitis through high-density genotyping of immune-related loci. Nat Genet, 45, 730-8.
COSTELLO, M. E., CICCIA, F., WILLNER, D., WARRINGTON, N., ROBINSON, P. C., GARDINER, B., MARSHALL, M., KENNA, T. J., TRIOLO, G. & BROWN, M. A. 2015. Brief Report: Intestinal Dysbiosis in Ankylosing Spondylitis. Arthritis Rheumatol, 67, 686-691.
CREEMERS, M. C., FRANSSEN, M. J., VAN'T HOF, M. A., GRIBNAU, F. W., VAN DE PUTTE, L. B. & VAN RIEL, P. L. 2005. Assessment of outcome in ankylosing spondylitis: an extended radiographic scoring system. Ann Rheum Dis, 64, 127-9.
CUA, D. J., SHERLOCK, J., CHEN, Y., MURPHY, C. A., JOYCE, B., SEYMOUR, B., LUCIAN, L., TO, W., KWAN, S., CHURAKOVA, T., ZURAWSKI, S., WIEKOWSKI, M., LIRA, S. A., GORMAN, D., KASTELEIN, R. A. & SEDGWICK, J. D. 2003. Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain. Nature, 421, 744-8.
CUI, N., HU, M. & KHALIL, R. A. 2017. Biochemical and Biological Attributes of Matrix Metalloproteinases. Progress in molecular biology and translational science, 147, 1-73.
DAOUSSIS, D., LIOSSIS, S. N., SOLOMOU, E. E., TSANAKTSI, A., BOUNIA, K., KARAMPETSOU, M., YIANNOPOULOS, G. & ANDONOPOULOS, A. P. 2010. Evidence that Dkk-1 is dysfunctional in ankylosing spondylitis. Arthritis Rheum, 62, 150-8.
DE ANDRADE, K. R., DE CASTRO, G. R., VICENTE, G., DA ROSA, J. S., NADER, M., PEREIRA, I. A. & FRODE, T. S. 2014. Evaluation of circulating levels of inflammatory and bone formation markers in axial spondyloarthritis. Int Immunopharmacol, 21, 481-6.
DE KONING, A., DE BRUIN, F., VAN DEN BERG, R., RAMIRO, S., BARALIAKOS, X., BRAUN, J., VAN GAALEN, F. A., REIJNIERSE, M. & VAN DER HEIJDE, D. 2018. Low-dose CT detects more progression of bone formation in comparison to conventional radiography in patients with ankylosing spondylitis: results from the SIAS cohort. Annals of the Rheumatic Diseases, 77, 293-299.
DE WINTER, J., DE HOOGE, M., VAN DE SANDE, M., DE JONG, H., VAN HOEVEN, L., DE KONING, A., BERG, I. J., RAMONDA, R., BAETEN, D., VAN DER HEIJDE, D., WEEL, A. & LANDEWE, R. 2018. Magnetic Resonance Imaging of the Sacroiliac Joints Indicating Sacroiliitis According to the Assessment of SpondyloArthritis international Society Definition in Healthy Individuals, Runners, and Women With Postpartum Back Pain. Arthritis Rheumatol, 70, 1042-1048.
DEAN, L. E., JONES, G. T., MACDONALD, A. G., DOWNHAM, C., STURROCK, R. D. & MACFARLANE, G. J. 2014. Global prevalence of ankylosing spondylitis. Rheumatology (Oxford), 53, 650-7.
DELAY, M. L., TURNER, M. J., KLENK, E. I., SMITH, J. A., SOWDERS, D. P. & COLBERT, R. A. 2009. HLA-B27 misfolding and the unfolded protein response augment interleukin-23 production and are associated with Th17 activation in transgenic rats. Arthritis Rheum, 60, 2633-43.
DERDEMEZIS, C. S., FILIPPATOS, T. D., VOULGARI, P. V., TSELEPIS, A. D., DROSOS, A. A. & KIORTSIS, D. N. 2010. Leptin and adiponectin levels in patients with ankylosing spondylitis. The effect of infliximab treatment. Clin Exp Rheumatol, 28, 880-3.
DIARRA, D., STOLINA, M., POLZER, K., ZWERINA, J., OMINSKY, M. S., DWYER, D., KORB, A., SMOLEN, J., HOFFMANN, M., SCHEINECKER, C., VAN DER HEIDE, D., LANDEWE, R., LACEY, D., RICHARDS, W. G. & SCHETT, G. 2007. Dickkopf-1 is a master regulator of joint remodeling. Nat Med, 13, 156-63.
DIAZ-PENA, R., ARANSAY, A. M., BRUGES-ARMAS, J., LOPEZ-VAZQUEZ, A., RODRIGUEZ-EZPELETA, N., MENDIBIL, I., SANCHEZ, A., TORRE-ALONSO, J. C., BETTENCOURT, B. F., MULERO, J., COLLANTES, E. & LOPEZ-LARREA, C. 2011. Fine mapping of a major histocompatibility complex in ankylosing spondylitis: association of the HLA-DPA1 and HLA-DPB1 regions. Arthritis Rheum, 63, 3305-12.
DOUGADOS, M., VAN DER LINDEN, S., JUHLIN, R., HUITFELDT, B., AMOR, B., CALIN, A., CATS, A., DIJKMANS, B., OLIVIERI, I., PASERO, G. & ET AL. 1991. The European Spondylarthropathy Study Group preliminary criteria for the classification of spondylarthropathy. Arthritis Rheum, 34, 1218-27.
EDMUNDS, L., ELSWOOD, J., KENNEDY, L. G. & CALIN, A. 1991. Primary ankylosing spondylitis, psoriatic and enteropathic spondyloarthropathy: a controlled analysis. J Rheumatol, 18, 696-8.
ERIKSEN, E. F. 2010. Cellular mechanisms of bone remodeling. Rev Endocr Metab Disord, 11, 219-27.
EUSTACE, S., KEOGH, C., BLAKE, M., WARD, R. J., ODER, P. D. & DIMASI, M. 2001. MR Imaging of Bone Oedema: Mechanisms and Interpretation: Pictorial Review. Clinical Radiology, 56, 4-12.
FILKOVA, M., JUNGEL, A., GAY, R. E. & GAY, S. 2012. MicroRNAs in rheumatoid arthritis: potential role in diagnosis and therapy. BioDrugs, 26, 131-41.
FOREJTOVA, S., MANN, H., STOLFA, J., VEDRAL, K., FENCLOVA, I., NEMETHOVA, D. & PAVELKA, K. 2008. Factors influencing health status and disability of patients with ankylosing spondylitis in the Czech Republic. Clin Rheumatol, 27, 1005-13.
FOSSIEZ, F., DJOSSOU, O., CHOMARAT, P., FLORES-ROMO, L., AIT-YAHIA, S., MAAT, C., PIN, J. J., GARRONE, P., GARCIA, E., SAELAND, S., BLANCHARD, D., GAILLARD, C., DAS MAHAPATRA, B., ROUVIER, E., GOLSTEIN, P., BANCHEREAU, J. & LEBECQUE, S. 1996. T cell interleukin-17 induces stromal cells to produce proinflammatory and hematopoietic cytokines. J Exp Med, 183, 2593-603.
GASTEIGER, G. & RUDENSKY, A. Y. 2014. Interactions between innate and adaptive lymphocytes. Nat Rev Immunol, 14, 631-9.
GHORESCHI, K., LAURENCE, A., YANG, X. P., TATO, C. M., MCGEACHY, M. J., KONKEL, J. E., RAMOS, H. L., WEI, L., DAVIDSON, T. S., BOULADOUX, N., GRAINGER, J. R., CHEN, Q., KANNO, Y., WATFORD, W. T., SUN, H. W., EBERL, G., SHEVACH, E. M., BELKAID, Y., CUA, D. J., CHEN, W. & O'SHEA, J. J. 2010. Generation of pathogenic T(H)17 cells in the absence of TGF-beta signalling. Nature, 467, 967-71.
GINALDI, L. & DE MARTINIS, M. 2016. Osteoimmunology and Beyond. Current medicinal chemistry, 23, 3754-3774.
GIRAUDO, C., WEBER, M., PUCHNER, A., GRISAR, J., KAINBERGER, F. & SCHUELLER-WEIDEKAMM, C. 2017. Which MR sequences should we use for the reliable detection and localization of bone marrow edema in spondyloarthritis? Radiol Med, 122, 752-760.
GOLDRING, S. R. & GOLDRING, M. B. 2007. Eating bone or adding it: the Wnt pathway decides. Nat Med, 13, 133-4.
GRATACOS, J., COLLADO, A., FILELLA, X., SANMARTI, R., CANETE, J., LLENA, J., MOLINA, R., BALLESTA, A. & MUNOZ-GOMEZ, J. 1994. Serum cytokines (IL-6, TNF-alpha, IL-1 beta and IFN-gamma) in ankylosing spondylitis: a close correlation between serum IL-6 and disease activity and severity. Br J Rheumatol, 33, 927-31.
GROBELNA, K. 2017. Spondyloartritidy:jejich genetická zátěž a dědičnost. Čes. Revmatol., 25, 85-90.
GUGLIELMI, G., SCALZO, G., CASCAVILLA, A., CAROTTI, M., SALAFFI, F. & GRASSI, W. 2009. Imaging of the sacroiliac joint involvement in seronegative spondylarthropathies. Clin Rheumatol, 28, 1007-19.
GUPTA, L., BHATTACHARYA, S. & AGGARWAL, A. 2018. Tenascin-C, a biomarker of disease activity in early ankylosing spondylitis. Clinical Rheumatology, 37, 1401-1405.
HARRINGTON, L. E., HATTON, R. D., MANGAN, P. R., TURNER, H., MURPHY, T. L., MURPHY, K. M. & WEAVER, C. T. 2005. Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat Immunol, 6, 1123-32.
HARTL, A., SIEPER, J., SYRBE, U., LISTING, J., HERMANN, K. G., RUDWALEIT, M. & PODDUBNYY, D. 2017. Serum levels of leptin and high molecular weight adiponectin are inversely associated with radiographic spinal progression in patients with ankylosing spondylitis: results from the ENRADAS trial. Arthritis Res Ther, 19, 140.
HASEGAWA, M., HIRATA, H., SUDO, A., KATO, K., KAWASE, D., KINOSHITA, N., YOSHIDA, T. & UCHIDA, A. 2004. Tenascin-C concentration in synovial fluid correlates with radiographic progression of knee osteoarthritis. J Rheumatol, 31, 2021-6.
HINZE, A. M., & LOUIE, G. H. 2016. Osteoporosis Management in Ankylosing Spondylitis. Current treatment options in rheumatology, 2(4), 271–282.
HUBER, M., HEINK, S., PAGENSTECHER, A., REINHARD, K., RITTER, J., VISEKRUNA, A., GURALNIK, A., BOLLIG, N., JELTSCH, K., HEINEMANN, C., WITTMANN, E., BUCH, T., PRAZERES DA COSTA, O., BRUSTLE, A., BRENNER, D., MAK, T. W., MITTRUCKER, H. W., TACKENBERG, B., KAMRADT, T. & LOHOFF, M. 2013. IL-17A secretion by CD8+ T cells supports Th17-mediated autoimmune encephalomyelitis. J Clin Invest, 123, 247-60.
CHAN, A. T., KOLLNBERGER, S. D., WEDDERBURN, L. R. & BOWNESS, P. 2005. Expansion and enhanced survival of natural killer cells expressing the killer immunoglobulin-like receptor KIR3DL2 in spondylarthritis. Arthritis Rheum, 52, 3586-95.
CHATZIKYRIAKIDOU, A., VOULGARI, P. V. & DROSOS, A. A. 2011. What is the role of HLA-B27 in spondyloarthropathies? Autoimmun Rev, 10, 464-8.
CHEN, B., LI, D. & XU, W. 2013. Association of ankylosing spondylitis with HLA-B27 and ERAP1: pathogenic role of antigenic peptide. Med Hypotheses, 80, 36-8.
CHEN, B., LI, J., HE, C., LI, D., TONG, W., ZOU, Y. & XU, W. 2017. Role of HLA-B27 in the pathogenesis of ankylosing spondylitis (Review). Mol Med Rep, 15, 1943-1951.
CHEN, H. A., CHEN, C. H., LIN, Y. J., CHEN, P. C., CHEN, W. S., LU, C. L. & CHOU, C. T. 2010. Association of bone morphogenetic proteins with spinal fusion in ankylosing spondylitis. J Rheumatol, 37, 2126-32.
CHEN, C. H., LIN, K. C., YU, D. T., YANG, C., HUANG, F., CHEN, H. A., LIANG, T. H., LIAO, H. T., TSAI, C. Y., WEI, J. C. & CHOU, C. T. 2006. Serum matrix metalloproteinases and tissue inhibitors of metalloproteinases in ankylosing spondylitis: MMP-3 is a reproducibly sensitive and specific biomarker of disease activity. Rheumatology (Oxford), 45, 414-20.
IVANOV, II, MCKENZIE, B. S., ZHOU, L., TADOKORO, C. E., LEPELLEY, A., LAFAILLE, J. J., CUA, D. J. & LITTMAN, D. R. 2006. The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell, 126, 1121-33.
JANS, L., VAN PRAET, L., ELEWAUT, D., VAN DEN BOSCH, F., CARRON, P., JAREMKO, J. L., BEHAEGHE, M., DENIS, A., HUYSSE, W., LAMBRECHT, V. & VERSTRAETE, K. 2014. MRI of the SI joints commonly shows non-inflammatory disease in patients clinically suspected of sacroiliitis. European Journal of Radiology, 83, 179-184.
JOO, Y. B., BANG, S. Y., KIM, T. H., SHIM, S. C., LEE, S., JOO, K. B., KIM, J. H., MIN, H. J., RAHMAN, P. & INMAN, R. D. 2014. Bone morphogenetic protein 6 polymorphisms are associated with radiographic progression in ankylosing spondylitis. PLoS One, 9, e104966.
KAPUSTIN, A. N. & SHANAHAN, C. M. 2011. Osteocalcin: a novel vascular metabolic and osteoinductive factor? Arterioscler Thromb Vasc Biol, 31, 2169-71.
KHAN, M. A. 1996. Epidemiology of HLA-B27 and Arthritis. Clin Rheumatol, 15 Suppl 1, 10-2.
KHAN, M. A. & VAN DER LINDEN, S. M. 1990. A wider spectrum of spondyloarthropathies. Semin Arthritis Rheum, 20, 107-13.
KHMELINSKII, N., REGEL, A. & BARALIAKOS, X. 2018. The Role of Imaging in Diagnosing Axial Spondyloarthritis. Frontiers in medicine, 5, 106-106.
KIM, T. H., STONE, M., PAYNE, U., ZHANG, X., IONESCU, M., LOBANOK, T., KING, L., POOLE, A. R. & INMAN, R. D. 2005. Cartilage biomarkers in ankylosing spondylitis: relationship to clinical variables and treatment response. Arthritis Rheum, 52, 885-91.
KJELGAARD-PETERSEN, C., SIEBUHR, A. S., CHRISTIANSEN, T., LADEL, C., KARSDAL, M. & BAY-JENSEN, A. C. 2015. Synovitis biomarkers: ex vivo characterization of three biomarkers for identification of inflammatory osteoarthritis. Biomarkers, 20, 547-56.
KOCABAS, H., KOCABAS, V., BUYUKBAS, S., MELIKOGLU, M. A., SEZER, I. & BUTUN, B. 2012. The serum levels of resistin in ankylosing spondylitis patients: a pilot study. Rheumatol Int, 32, 699-702.
KOENDERS, M., LUBBERTS, E., WALGREEN, B., BERSSELAAR, L. A., HELSEN, M., PADOVA, F., BOOTS, A., GRAM, H., JOOSTEN, L. & BERG, W. 2005a. Blocking of Interleukin-17 during Reactivation of Experimental Arthritis Prevents Joint Inflammation and Bone Erosion by Decreasing RANKL and Interleukin-1. The American journal of pathology, 167, 141-9.
KOENDERS, M. I., KOLLS, J. K., OPPERS-WALGREEN, B., VAN DEN BERSSELAAR, L., JOOSTEN, L. A., SCHURR, J. R., SCHWARZENBERGER, P., VAN DEN BERG, W. B. & LUBBERTS, E. 2005b. Interleukin-17 receptor deficiency results in impaired synovial expression of interleukin-1 and matrix metalloproteinases 3, 9, and 13 and prevents cartilage destruction during chronic reactivated streptococcal cell wall-induced arthritis. Arthritis Rheum, 52, 3239-47.
KOPPLIN, L. J., MOUNT, G. & SUHLER, E. B. 2016. Review for Disease of the Year: Epidemiology of HLA-B27 Associated Ocular Disorders. Ocular immunology and inflammation, 24, 470-475.
LA CAVA, A. & MATARESE, G. 2004. The weight of leptin in immunity. Nat Rev Immunol, 4, 371-9.
LACEY, D. L., TIMMS, E., TAN, H. L., KELLEY, M. J., DUNSTAN, C. R., BURGESS, T., ELLIOTT, R., COLOMBERO, A., ELLIOTT, G., SCULLY, S., HSU, H., SULLIVAN, J., HAWKINS, N., DAVY, E., CAPPARELLI, C., ELI, A., QIAN, Y. X., KAUFMAN, S., SAROSI, I., SHALHOUB, V., SENALDI, G., GUO, J., DELANEY, J. & BOYLE, W. J. 1998. Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell, 93, 165-76.
LAMBERT, R. G., BAKKER, P. A., VAN DER HEIJDE, D., WEBER, U., RUDWALEIT, M., HERMANN, K. G., SIEPER, J., BARALIAKOS, X., BENNETT, A., BRAUN, J., BURGOS-VARGAS, R., DOUGADOS, M., PEDERSEN, S. J., JURIK, A. G., MAKSYMOWYCH, W. P., MARZO-ORTEGA, H., OSTERGAARD, M., PODDUBNYY, D., REIJNIERSE, M., VAN DEN BOSCH, F., VAN DER HORST-BRUINSMA, I. & LANDEWE, R. 2016. Defining active sacroiliitis on MRI for classification of axial spondyloarthritis: update by the ASAS MRI working group. Ann Rheum Dis, 75, 1958-1963.
LEE, Y.-A., CHOI, H. M., LEE, S.-H., YANG, H.-I., YOO, M. C., HONG, S.-J. & KIM, K. S. 2012. Synergy between adiponectin and interleukin-1β on the expression of interleukin-6, interleukin-8, and cyclooxygenase-2 in fibroblast-like synoviocytes. Experimental & Molecular Medicine, 44, 440-447.
LEE, Y. H. & SONG, G. G. 2016. Associations between ERAP1 polymorphisms and susceptibility to ankylosing spondylitis: a meta-analysis. Clin Rheumatol, 35, 2009-15.
LEIJTEN, E. F., VAN KEMPEN, T. S., BOES, M., MICHELS-VAN AMELSFORT, J. M., HIJNEN, D., HARTGRING, S. A., VAN ROON, J. A., WENINK, M. H. & RADSTAKE, T. R. 2015. Brief report: enrichment of activated group 3 innate lymphoid cells in psoriatic arthritis synovial fluid. Arthritis Rheumatol, 67, 2673-8.
LEONARDI, R., BARBATO, E., PAGANELLI, C. & LO MUZIO, L. 2004. Immunolocalization of heat shock protein 27 in developing jaw bones and tooth germs of human fetuses. Calcif Tissue Int, 75, 509-16.
LIN, P., BACH, M., ASQUITH, M., LEE, A. Y., AKILESWARAN, L., STAUFFER, P., DAVIN, S., PAN, Y., CAMBRONNE, E. D., DORRIS, M., DEBELIUS, J. W., LAUBER, C. L., ACKERMANN, G., BAEZA, Y. V., GILL, T., KNIGHT, R., COLBERT, R. A., TAUROG, J. D., VAN GELDER, R. N. & ROSENBAUM, J. T. 2014. HLA-B27 and human beta2-microglobulin affect the gut microbiota of transgenic rats. PLoS One, 9, e105684.
LINDQUIST, S. & CRAIG, E. A. 1988. The heat-shock proteins. Annu Rev Genet, 22, 631-77.
LIU, K. G., HE, Q. H., TAN, J. W. & LIAO, G. J. 2015. Expression of TNF-alpha, VEGF, and MMP-3 mRNAs in synovial tissues and their roles in fibroblast-mediated osteogenesis in ankylosing spondylitis. Genet Mol Res, 14, 6852-8.
LOPEZ-LARREA, C., SUJIRACHATO, K., MEHRA, N. K., CHIEWSILP, P., ISARANGKURA, D., KANGA, U., DOMINGUEZ, O., COTO, E., PENA, M., SETIEN, F. & ET AL. 1995. HLA-B27 subtypes in Asian patients with ankylosing spondylitis. Evidence for new associations. Tissue Antigens, 45, 169-76.
LORIES, R. J., DERESE, I., CEUPPENS, J. L. & LUYTEN, F. P. 2003. Bone morphogenetic proteins 2 and 6, expressed in arthritic synovium, are regulated by proinflammatory cytokines and differentially modulate fibroblast-like synoviocyte apoptosis. Arthritis Rheum, 48, 2807-18.
LORIES, R. J., DERESE, I. & LUYTEN, F. P. 2005. Modulation of bone morphogenetic protein signaling inhibits the onset and progression of ankylosing enthesitis. J Clin Invest, 115, 1571-9.
MACLEAN, I. L., IQBALL, S., WOO, P., KEAT, A. C., HUGHES, R. A., KINGSLEY, G. H. & KNIGHT, S. C. 1993. HLA-B27 subtypes in the spondarthropathies. Clin Exp Immunol, 91, 214-9.
MAGREY, M. N. & KHAN, M. A. 2017. The Paradox of Bone Formation and Bone Loss in Ankylosing Spondylitis: Evolving New Concepts of Bone Formation and Future Trends in Management. Curr Rheumatol Rep, 19, 17.
MAKSYMOWYCH, W., WICHUK, S., CHIOWCHANWISAWAKIT, P., LAMBERT, R. & PEDERSEN, S. 2014. Fat Metaplasia and Backfill Are Key Intermediaries in the Development of Sacroiliac Joint Ankylosis in Patients With Ankylosing Spondylitis. Arthritis & Rheumatology, 66.
MAKSYMOWYCH, W. P. 2012. MRI and X-ray in axial spondyloarthritis: the relationship between inflammatory and structural changes. Arthritis research & therapy, 14, 207-207.
MAKSYMOWYCH, W. P., INMAN, R. D., SALONEN, D., DHILLON, S. S., WILLIAMS, M., STONE, M., CONNER-SPADY, B., PALSAT, J. & LAMBERT, R. G. 2005. Spondyloarthritis research Consortium of Canada magnetic resonance imaging index for assessment of sacroiliac joint inflammation in ankylosing spondylitis. Arthritis Rheum, 53, 703-9.
MAKSYMOWYCH, W. P., LANDEWE, R., CONNER-SPADY, B., DOUGADOS, M., MIELANTS, H., VAN DER TEMPEL, H., POOLE, A. R., WANG, N. & VAN DER HEIJDE, D. 2007. Serum matrix metalloproteinase 3 is an independent predictor of structural damage progression in patients with ankylosing spondylitis. Arthritis Rheum, 56, 1846-53.
MANDL, P., NAVARRO-COMPÁN, V., TERSLEV, L., AEGERTER, P., VAN DER HEIJDE, D., D'AGOSTINO, M. A., BARALIAKOS, X., PEDERSEN, S. J., JURIK, A. G., NAREDO, E., SCHUELLER-WEIDEKAMM, C., WEBER, U., WICK, M. C., BAKKER, P. A. C., FILIPPUCCI, E., CONAGHAN, P. G., RUDWALEIT, M., SCHETT, G., SIEPER, J., TARP, S., MARZO-ORTEGA, H. & ØSTERGAARD, M. 2015. EULAR recommendations for the use of imaging in the diagnosis and management of spondyloarthritis in clinical practice. Annals of the Rheumatic Diseases.
MARUOTTI, N., CORRADO, A., NEVE, A. & CANTATORE, F. P. 2013. Systemic effects of Wnt signaling. J Cell Physiol, 228, 1428-32.
MATARESE, G., LA CAVA, A., SANNA, V., LORD, G. M., LECHLER, R. I., FONTANA, S. & ZAPPACOSTA, S. 2002. Balancing susceptibility to infection and autoimmunity: a role for leptin? Trends Immunol, 23, 182-7.
MATHSSON, L., MULLAZEHI, M., WICK, M. C., SJOBERG, O., VAN VOLLENHOVEN, R., KLARESKOG, L. & RONNELID, J. 2008. Antibodies against citrullinated vimentin in rheumatoid arthritis: higher sensitivity and extended prognostic value concerning future radiographic progression as compared with antibodies against cyclic citrullinated peptides. Arthritis Rheum, 58, 36-45.
MATTEY, D. L., PACKHAM, J. C., NIXON, N. B., COATES, L., CREAMER, P., HAILWOOD, S., TAYLOR, G. J. & BHALLA, A. K. 2012. Association of cytokine and matrix metalloproteinase profiles with disease activity and function in ankylosing spondylitis. Arthritis Res Ther, 14, R127.
MEI, Y., PAN, F., GAO, J., GE, R., DUAN, Z., ZENG, Z., LIAO, F., XIA, G., WANG, S., XU, S., XU, J., ZHANG, L. & YE, D. 2011. Increased serum IL-17 and IL-23 in the patient with ankylosing spondylitis. Clin Rheumatol, 30, 269-73.
MIDWOOD, K., SACRE, S., PICCININI, A. M., INGLIS, J., TREBAUL, A., CHAN, E., DREXLER, S., SOFAT, N., KASHIWAGI, M., OREND, G., BRENNAN, F. & FOXWELL, B. 2009. Tenascin-C is an endogenous activator of Toll-like receptor 4 that is essential for maintaining inflammation in arthritic joint disease. Nat Med, 15, 774-80.
MIDWOOD, K. S., CHIQUET, M., TUCKER, R. P. & OREND, G. 2016. Tenascin-C at a glance. J Cell Sci, 129, 4321-4327.
MIDWOOD, K. S. & OREND, G. 2009. The role of tenascin-C in tissue injury and tumorigenesis. J Cell Commun Signal, 3, 287-310.
MIELANTS, H., VEYS, E. M., CUVELIER, C. & DE VOS, M. 1988. Ileocolonoscopic findings in seronegative spondylarthropathies. Br J Rheumatol, 27 Suppl 2, 95-105.
MINOTA, S., KOYASU, S., YAHARA, I. & WINFIELD, J. 1988. Autoantibodies to the heat-shock protein hsp90 in systemic lupus erythematosus. J Clin Invest, 81, 106-9.
MIRANDA-FILLOY, J. A., LOPEZ-MEJIAS, R., GENRE, F., CARNERO-LOPEZ, B., OCHOA, R., DIAZ DE TERAN, T., GONZALEZ-JUANATEY, C., BLANCO, R., LLORCA, J. & GONZALEZ-GAY, M. A. 2013a. Adiponectin and resistin serum levels in non-diabetic ankylosing spondylitis patients undergoing TNF-alpha antagonist therapy. Clin Exp Rheumatol, 31, 365-71.
MIRANDA-FILLOY, J. A., LOPEZ-MEJIAS, R., GENRE, F., CARNERO-LOPEZ, B., OCHOA, R., DIAZ DE TERAN, T., GONZALEZ-JUANATEY, C., BLANCO, R., LLORCA, J. & GONZALEZ-GAY, M. A. 2013b. Leptin and visfatin serum levels in non-diabetic ankylosing spondylitis patients undergoing TNF-alpha antagonist therapy. Clin Exp Rheumatol, 31, 538-45.
MITRA, R. 2009. Osteitis Condensans Ilii. Rheumatology International, 30, 293-296.
MIYASAKA, M., NAKATA, H., HAO, J., KIM, Y.-K., KASUGAI, S. & KURODA, S. 2015. Low-Intensity Pulsed Ultrasound Stimulation Enhances Heat-Shock Protein 90 and Mineralized Nodule Formation in Mouse Calvaria-Derived Osteoblasts. Tissue engineering. Part A, 21, 2829-2839.
MOISAN, E. & GIRARD, D. 2006. Cell surface expression of intermediate filament proteins vimentin and lamin B1 in human neutrophil spontaneous apoptosis. Journal of Leukocyte Biology, 79, 489-498.
MORTENSEN, J. H., GODSKESEN, L. E., JENSEN, M. D., VAN HAAFTEN, W. T., KLINGE, L. G., OLINGA, P., DIJKSTRA, G., KJELDSEN, J., KARSDAL, M. A., BAY-JENSEN, A. C. & KRAG, A. 2015. Fragments of Citrullinated and MMP-degraded Vimentin and MMP-degraded Type III Collagen Are Novel Serological Biomarkers to Differentiate Crohn's Disease from Ulcerative Colitis. J Crohns Colitis, 9, 863-72.
MOSCHEN, A. R., GEIGER, S., GERNER, R. & TILG, H. 2010. Pre-B cell colony enhancing factor/NAMPT/visfatin and its role in inflammation-related bone disease. Mutat Res, 690, 95-101.
MOSCHEN, A. R., KASER, A., ENRICH, B., MOSHEIMER, B., THEURL, M., NIEDEREGGER, H. & TILG, H. 2007. Visfatin, an adipocytokine with proinflammatory and immunomodulating properties. J Immunol, 178, 1748-58.
MUSAELYAN, A., LAPIN, S., NAZAROV, V., TKACHENKO, O., GILBURD, B., MAZING, A., MIKHAILOVA, L. & SHOENFELD, Y. 2018. Vimentin as antigenic target in autoimmunity: A comprehensive review. Autoimmun Rev, 17, 926-934.
NAOT, D., MUSSON, D. S. & CORNISH, J. 2017. The Activity of Adiponectin in Bone. Calcif Tissue Int, 100, 486-499.
NEGISHI-KOGA, T., SHINOHARA, M., KOMATSU, N., BITO, H., KODAMA, T., FRIEDEL, R. H. & TAKAYANAGI, H. 2011. Suppression of bone formation by osteoclastic expression of semaphorin 4D. Nat Med, 17, 1473-80.
NEUMANN, E., FROMMER, K. W., VASILE, M. & MÜLLER-LADNER, U. 2011. Adipocytokines as driving forces in rheumatoid arthritis and related inflammatory diseases? Arthritis & Rheumatism, 63, 1159-1169.
NISTALA, H., LEE-ARTEAGA, S., SICILIANO, G., SMALDONE, S. & RAMIREZ, F. 2010. Extracellular regulation of transforming growth factor beta and bone morphogenetic protein signaling in bone. Ann N Y Acad Sci, 1192, 253-6.
NORTON, P. M., ISENBERG, D. A. & LATCHMAN, D. S. 1989. Elevated levels of the 90 kd heat shock protein in a proportion of SLE patients with active disease. J Autoimmun, 2, 187-95.
NUMASAKI, M., FUKUSHI, J., ONO, M., NARULA, S. K., ZAVODNY, P. J., KUDO, T., ROBBINS, P. D., TAHARA, H. & LOTZE, M. T. 2003. Interleukin-17 promotes angiogenesis and tumor growth. Blood, 101, 2620-7.
OSTA, B., LAVOCAT, F., ELJAAFARI, A. & MIOSSEC, P. 2014. Effects of Interleukin-17A on Osteogenic Differentiation of Isolated Human Mesenchymal Stem Cells. Frontiers in immunology, 5, 425-425.
OTERO, M., LAGO, R., GOMEZ, R., LAGO, F., DIEGUEZ, C., GOMEZ-REINO, J. J. & GUALILLO, O. 2006. Changes in plasma levels of fat-derived hormones adiponectin, leptin, resistin and visfatin in patients with rheumatoid arthritis. Ann Rheum Dis, 65, 1198-201.
PAGE, T. H., CHARLES, P. J., PICCININI, A. M., NICOLAIDOU, V., TAYLOR, P. C. & MIDWOOD, K. S. 2012. Raised circulating tenascin-C in rheumatoid arthritis. Arthritis Res Ther, 14, R260.
PARKES, M., CORTES, A., VAN HEEL, D. A. & BROWN, M. A. 2013. Genetic insights into common pathways and complex relationships among immune-mediated diseases. Nat Rev Genet, 14, 661-73.
PEDERSEN, S. J., HETLAND, M. L., SORENSEN, I. J., OSTERGAARD, M., NIELSEN, H. J. & JOHANSEN, J. S. 2010. Circulating levels of interleukin-6, vascular endothelial growth factor, YKL-40, matrix metalloproteinase-3, and total aggrecan in spondyloarthritis patients during 3 years of treatment with TNFalpha inhibitors. Clin Rheumatol, 29, 1301-9.
PEDERSEN, S. J., SØRENSEN, I. J., LAMBERT, R. G. W., HERMANN, K.-G. A., GARNERO, P., JOHANSEN, J. S., MADSEN, O. R., HANSEN, A., HANSEN, M. S., THAMSBORG, G., ANDERSEN, L. S., MAJGAARD, O., LOFT, A. G., ERLENDSSON, J., ASMUSSEN, K. H., JURIK, A. G., MØLLER, J., HASSELQUIST, M., MIKKELSEN, D. & ØSTERGAARD, M. 2011. Radiographic progression is associated with resolution of systemic inflammation in patients with axial spondylarthritis treated with tumor necrosis factor α inhibitors: A study of radiographic progression, inflammation on magnetic resonance imaging, and circulating biomarkers of inflammation, angiogenesis, and cartilage and bone turnover. Arthritis & Rheumatism, 63, 3789-3800.
PETTIT, A. R., JI, H., VON STECHOW, D., MULLER, R., GOLDRING, S. R., CHOI, Y., BENOIST, C. & GRAVALLESE, E. M. 2001. TRANCE/RANKL knockout mice are protected from bone erosion in a serum transfer model of arthritis. Am J Pathol, 159, 1689-99.
PODDUBNYY, D., HAIBEL, H., LISTING, J., MARKER-HERMANN, E., ZEIDLER, H., BRAUN, J., SIEPER, J. & RUDWALEIT, M. 2012. Baseline radiographic damage, elevated acute-phase reactant levels, and cigarette smoking status predict spinal radiographic progression in early axial spondylarthritis. Arthritis Rheum, 64, 1388-98.
PONZETTI, M. & RUCCI, N. 2019. Updates on Osteoimmunology: What's New on the Cross-Talk Between Bone and Immune System. Frontiers in endocrinology, 10, 236-236.
PRAJZLEROVA, K., GROBELNA, K., PAVELKA, K., SENOLT, L. & FILKOVA, M. 2016. An update on biomarkers in axial spondyloarthritis. Autoimmun Rev.
PROCHÁZKOVÁ, L., HULEJOVÁ, J., NĚMEC, P. & ŠENOLT, L. 2013. Circulating Heat Shock Protein 90 (HSP90) in patients with rheumatoid arthritis and axial spondylarthritis.
RAGGATT, L. J., QIN, L., TAMASI, J., JEFCOAT, S. C., JR., SHIMIZU, E., SELVAMURUGAN, N., LIEW, F. Y., BEVELOCK, L., FEYEN, J. H. & PARTRIDGE, N. C. 2008. Interleukin-18 is regulated by parathyroid hormone and is required for its bone anabolic actions. J Biol Chem, 283, 6790-8.
RAHMAN, P., INMAN, R. D., GLADMAN, D. D., REEVE, J. P., PEDDLE, L. & MAKSYMOWYCH, W. P. 2008. Association of interleukin-23 receptor variants with ankylosing spondylitis. Arthritis Rheum, 58, 1020-5.
RAMIRO, S., CLAUDEPIERRE, P., SEPRIANO, A., VAN LUNTEREN, M., MOLTO, A., FEYDY, A., ANTONIETTA D'AGOSTINO, M., LOEUILLE, D., DOUGADOS, M., REIJNIERSE, M. & VAN DER HEIJDE, D. 2018. Which scoring method depicts spinal radiographic damage in early axial spondyloarthritis best? Five-year results from the DESIR cohort. Rheumatology (Oxford), 57, 1991-2000.
RAYCHAUDHURI, S. K., SAXENA, A. & RAYCHAUDHURI, S. P. 2015. Role of IL-17 in the pathogenesis of psoriatic arthritis and axial spondyloarthritis. Clin Rheumatol, 34, 1019-23.
REDLICH, K., HAYER, S., RICCI, R., DAVID, J. P., TOHIDAST-AKRAD, M., KOLLIAS, G., STEINER, G., SMOLEN, J. S., WAGNER, E. F. & SCHETT, G. 2002. Osteoclasts are essential for TNF-alpha-mediated joint destruction. J Clin Invest, 110, 1419-27.
REVEILLE, J. D., INMAN, R., KHAN, M., YU, D. T. K. & JIN, L. 2000. Family studies in ankylosing spondylitis: microsatellite analysis of 55 concordant sib pairs. J Rheumatol, 27(Suppl 59).
REVEILLE, J. D., SIMS, A. M., DANOY, P., EVANS, D. M., LEO, P., POINTON, J. J., JIN, R., ZHOU, X., BRADBURY, L. A., APPLETON, L. H., DAVIS, J. C., DIEKMAN, L., DOAN, T., DOWLING, A., DUAN, R., DUNCAN, E. L., FARRAR, C., HADLER, J., HARVEY, D., KARADERI, T., MOGG, R., POMEROY, E., PRYCE, K., TAYLOR, J., SAVAGE, L., DELOUKAS, P., KUMANDURI, V., PELTONEN, L., RING, S. M., WHITTAKER, P., GLAZOV, E., THOMAS, G. P., MAKSYMOWYCH, W. P., INMAN, R. D., WARD, M. M., STONE, M. A., WEISMAN, M. H., WORDSWORTH, B. P. & BROWN, M. A. 2010. Genome-wide association study of ankylosing spondylitis identifies non-MHC susceptibility loci. Nat Genet, 42, 123-7.
REYNOLDS, T. L., KHAN, M. A., VAN DER LINDEN, S. & CLEVELAND, R. P. 1991. Differences in HLA-B27 positive and negative patients with ankylosing spondylitis: study of clinical disease activity and concentrations of serum IgA, C reactive protein, and haptoglobin. Annals of the rheumatic diseases, 50, 154-157.
RIPLEY, B. J., ISENBERG, D. A. & LATCHMAN, D. S. 2001. Elevated levels of the 90 kDa heat shock protein (hsp90) in SLE correlate with levels of IL-6 and autoantibodies to hsp90. J Autoimmun, 17, 341-6.
ROBINSON, P. C., BIRD, P., LIM, I., SAAD, N., SCHACHNA, L., TAYLOR, A. L., WHITTLE, S. L. & BROWN, M. A. 2014. Consensus statement on the investigation and management of non-radiographic axial spondyloarthritis (nr-axSpA). Int J Rheum Dis, 17, 548-56.
ROBINSON, P. C. & BROWN, M. A. 2014. Genetics of ankylosing spondylitis. Molecular Immunology, 57, 2-11.
ROVIN, B. H., SONG, H., HEBERT, L. A., NADASDY, T., NADASDY, G., BIRMINGHAM, D. J., YUNG YU, C. & NAGARAJA, H. N. 2005. Plasma, urine, and renal expression of adiponectin in human systemic lupus erythematosus. Kidney Int, 68, 1825-33.
RUDWALEIT, M., BRAUN, J., SIEPER, J. & ASSESSMENT OF SPONDYLOARTHRITIS INTERNATIONAL, S. 2009a. [ASAS classification criteria for axial spondyloarthritis]. Z Rheumatol, 68, 591-3.
RUDWALEIT, M., HAIBEL, H., BARALIAKOS, X., LISTING, J., MARKER-HERMANN, E., ZEIDLER, H., BRAUN, J. & SIEPER, J. 2009b. The early disease stage in axial spondylarthritis: results from the German Spondyloarthritis Inception Cohort. Arthritis Rheum, 60, 717-27.
RUDWALEIT, M., JURIK, A. G., HERMANN, K. G., LANDEWE, R., VAN DER HEIJDE, D., BARALIAKOS, X., MARZO-ORTEGA, H., OSTERGAARD, M., BRAUN, J. & SIEPER, J. 2009c. Defining active sacroiliitis on magnetic resonance imaging (MRI) for classification of axial spondyloarthritis: a consensual approach by the ASAS/OMERACT MRI group. Ann Rheum Dis, 68, 1520-7.
RUDWALEIT, M., METTER, A., LISTING, J., SIEPER, J. & BRAUN, J. 2006. Inflammatory back pain in ankylosing spondylitis: a reassessment of the clinical history for application as classification and diagnostic criteria. Arthritis Rheum, 54, 569-78.
RUDWALEIT, M., VAN DER HEIJDE, D., LANDEWÉ, R., AKKOC, N., BRANDT, J., CHOU, C. T., DOUGADOS, M., HUANG, F., GU, J., KIRAZLI, Y., VAN DEN BOSCH, F., OLIVIERI, I., ROUSSOU, E., SCARPATO, S., SØRENSEN, I. J., VALLE-OÑATE, R., WEBER, U., WEI, J. & SIEPER, J. 2011. The Assessment of SpondyloArthritis international Society classification criteria for peripheral spondyloarthritis and for spondyloarthritis in general. Annals of the Rheumatic Diseases, 70, 25-31.
RUHMANN, M., PICCININI, A. M., KONG, P. L. & MIDWOOD, K. S. 2012. Endogenous activation of adaptive immunity: tenascin-C drives interleukin-17 synthesis in murine arthritic joint disease. Arthritis Rheum, 64, 2179-90.
SALEH, H., EELES, D., HODGE, J. M., NICHOLSON, G. C., GU, R., POMPOLO, S., GILLESPIE, M. T. & QUINN, J. M. 2011. Interleukin-33, a target of parathyroid hormone and oncostatin m, increases osteoblastic matrix mineral deposition and inhibits osteoclast formation in vitro. Endocrinology, 152, 1911-22.
SATO, A., AONUMA, K., IMANAKA-YOSHIDA, K., YOSHIDA, T., ISOBE, M., KAWASE, D., KINOSHITA, N., YAZAKI, Y. & HIROE, M. 2006. Serum tenascin-C might be a novel predictor of left ventricular remodeling and prognosis after acute myocardial infarction. J Am Coll Cardiol, 47, 2319-25.
SAXENA, A., RAYCHAUDHURI, S. K. & RAYCHAUDHURI, S. P. 2011. Interleukin-17-induced proliferation of fibroblast-like synovial cells is mTOR dependent. Arthritis Rheum, 63, 1465-6.
SHERLOCK, J. P., JOYCE-SHAIKH, B., TURNER, S. P., CHAO, C. C., SATHE, M., GREIN, J., GORMAN, D. M., BOWMAN, E. P., MCCLANAHAN, T. K., YEARLEY, J. H., EBERL, G., BUCKLEY, C. D., KASTELEIN, R. A., PIERCE, R. H., LAFACE, D. M. & CUA, D. J. 2012. IL-23 induces spondyloarthropathy by acting on ROR-gammat+ CD3+CD4-CD8- entheseal resident T cells. Nat Med, 18, 1069-76.
SHUKLA, A., GAUR, P. & AGGARWAL, A. 2015. Tenascin-C Levels, A Toll-like Receptor 4 Ligand, in Enthesitis-related Arthritis Category of Juvenile Idiopathic Arthritis: A Cross-sectional and Longitudinal Study. J Rheumatol, 42, 891-6.
SCHWARZENBERGER, P., LA RUSSA, V., MILLER, A., YE, P., HUANG, W., ZIESKE, A., NELSON, S., BAGBY, G. J., STOLTZ, D., MYNATT, R. L., SPRIGGS, M. & KOLLS, J. K. 1998. IL-17 stimulates granulopoiesis in mice: use of an alternate, novel gene therapy-derived method for in vivo evaluation of cytokines. J Immunol, 161, 6383-9.
SIEPER, J., LISTING, J., PODDUBNYY, D., SONG, I.-H., HERMANN, K.-G., CALLHOFF, J., SYRBE, U., BRAUN, J. & RUDWALEIT, M. 2016. Effect of continuous versus on-demand treatment of ankylosing spondylitis with diclofenac over 2 years on radiographic progression of the spine: results from a randomised multicentre trial (ENRADAS). Annals of the Rheumatic Diseases, 75, 1438-1443.
SIEPER, J. & PODDUBNYY, D. 2017. Axial spondyloarthritis. Lancet, 390, 73-84.
SIEPER, J., RUDWALEIT, M., BARALIAKOS, X., BRANDT, J., BRAUN, J., BURGOS-VARGAS, R., DOUGADOS, M., HERMANN, K. G., LANDEWE, R., MAKSYMOWYCH, W. & VAN DER HEIJDE, D. 2009a. The Assessment of SpondyloArthritis international Society (ASAS) handbook: a guide to assess spondyloarthritis. Ann Rheum Dis, 68 Suppl 2, ii1-44.
SIEPER, J., VAN DER HEIJDE, D., LANDEWE, R., BRANDT, J., BURGOS-VAGAS, R., COLLANTES-ESTEVEZ, E., DIJKMANS, B., DOUGADOS, M., KHAN, M. A., LEIRISALO-REPO, M., VAN DER LINDEN, S., MAKSYMOWYCH, W. P., MIELANTS, H., OLIVIERI, I. & RUDWALEIT, M. 2009b. New criteria for inflammatory back pain in patients with chronic back pain: a real patient exercise by experts from the Assessment of SpondyloArthritis international Society (ASAS). Ann Rheum Dis, 68, 784-8.
SIMS, A. M., BARNARDO, M., HERZBERG, I., BRADBURY, L., CALIN, A., WORDSWORTH, B. P., DARKE, C. & BROWN, M. A. 2007. Non-B27 MHC associations of ankylosing spondylitis. Genes Immun, 8, 115-23.
SONG, I. H., HERMANN, K. G., HAIBEL, H., ALTHOFF, C. E., PODDUBNYY, D., LISTING, J., WEISS, A., FREUNDLICH, B., RUDWALEIT, M. & SIEPER, J. 2011. Relationship between active inflammatory lesions in the spine and sacroiliac joints and new development of chronic lesions on whole-body MRI in early axial spondyloarthritis: results of the ESTHER trial at week 48. Ann Rheum Dis, 70, 1257-63.
SONOMOTO, K., YAMAOKA, K., OSHITA, K., FUKUYO, S., ZHANG, X., NAKANO, K., OKADA, Y. & TANAKA, Y. 2012. Interleukin-1beta induces differentiation of human mesenchymal stem cells into osteoblasts via the Wnt-5a/receptor tyrosine kinase-like orphan receptor 2 pathway. Arthritis Rheum, 64, 3355-63.
STOLWIJK, C., VAN TUBERGEN, A., CASTILLO-ORTIZ, J. D. & BOONEN, A. 2015. Prevalence of extra-articular manifestations in patients with ankylosing spondylitis: a systematic review and meta-analysis. Ann Rheum Dis, 74, 65-73.
SUN, S., BAY-JENSEN, A. C., KARSDAL, M. A., SIEBUHR, A. S., ZHENG, Q., MAKSYMOWYCH, W. P., CHRISTIANSEN, T. G. & HENRIKSEN, K. 2014. The active form of MMP-3 is a marker of synovial inflammation and cartilage turnover in inflammatory joint diseases. BMC Musculoskelet Disord, 15, 93.
SUTTON, C. E., LALOR, S. J., SWEENEY, C. M., BRERETON, C. F., LAVELLE, E. C. & MILLS, K. H. 2009. Interleukin-1 and IL-23 induce innate IL-17 production from gammadelta T cells, amplifying Th17 responses and autoimmunity. Immunity, 31, 331-41.
SYRBE, U., CALLHOFF, J., CONRAD, K., PODDUBNYY, D., HAIBEL, H., JUNKER, S., FROMMER, K. W., MULLER-LADNER, U., NEUMANN, E. & SIEPER, J. 2015. Serum adipokine levels in patients with ankylosing spondylitis and their relationship to clinical parameters and radiographic spinal progression. Arthritis Rheumatol, 67, 678-85.
TANAKA, H., EL-KAREF, A., KAITO, M., KINOSHITA, N., FUJITA, N., HORIIKE, S., WATANABE, S., YOSHIDA, T. & ADACHI, Y. 2006. Circulating level of large splice variants of tenascin-C is a marker of piecemeal necrosis activity in patients with chronic hepatitis C. Liver Int, 26, 311-8.
TAS, F., BILGIN, E., ERTURK, K. & DURANYILDIZ, D. 2017. Clinical Significance of Circulating Serum Cellular Heat Shock Protein 90 (HSP90) Level in Patients with Cutaneous Malignant Melanoma. Asian Pac J Cancer Prev, 18, 599-601.
THOMMESEN, L., STUNES, A. K., MONJO, M., GROSVIK, K., TAMBURSTUEN, M. V., KJOBLI, E., LYNGSTADAAS, S. P., RESELAND, J. E. & SYVERSEN, U. 2006. Expression and regulation of resistin in osteoblasts and osteoclasts indicate a role in bone metabolism. J Cell Biochem, 99, 824-34.
TOMCIK, M., ZERR, P., PITKOWSKI, J., PALUMBO-ZERR, K., AVOUAC, J., DISTLER, O., BECVAR, R., SENOLT, L., SCHETT, G. & DISTLER, J. H. 2014. Heat shock protein 90 (Hsp90) inhibition targets canonical TGF-beta signalling to prevent fibrosis. Ann Rheum Dis, 73, 1215-22.
TRIANTAFILOU, K., TRIANTAFILOU, M. & DEDRICK, R. L. 2001. A CD14-independent LPS receptor cluster. Nat Immunol, 2, 338-45.
TSAN, M. F. & GAO, B. 2004. Heat shock protein and innate immunity. Cell Mol Immunol, 1, 274-9.
TSENG, H. W., PITT, M. E., GLANT, T. T., MCRAE, A. F., KENNA, T. J., BROWN, M. A., PETTIT, A. R. & THOMAS, G. P. 2016. Inflammation-driven bone formation in a mouse model of ankylosing spondylitis: sequential not parallel processes. Arthritis Res Ther, 18, 35.
UCHANSKA-ZIEGLER, B. & ZIEGLER, A. 2003. Ankylosing spondylitis: a beta2m-deposition disease? Trends Immunol, 24, 73-6.
USTUN, N., TOK, F., KALYONCU, U., MOTOR, S., YUKSEL, R., YAGIZ, A. E., GULER, H. & TURHANOGLU, A. D. 2014. Sclerostin and Dkk-1 in patients with ankylosing spondylitis. Acta Reumatol Port, 39, 146-51.
VAN DER HEIJDE, D., RAMIRO, S., LANDEWÉ, R., BARALIAKOS, X., VAN DEN BOSCH, F., SEPRIANO, A., REGEL, A., CIUREA, A., DAGFINRUD, H., DOUGADOS, M., VAN GAALEN, F., GÉHER, P., VAN DER HORST-BRUINSMA, I., INMAN, R. D., JONGKEES, M., KILTZ, U., KVIEN, T. K., MACHADO, P. M., MARZO-ORTEGA, H., MOLTO, A., NAVARRO-COMPÀN, V., OZGOCMEN, S., PIMENTEL-SANTOS, F. M., REVEILLE, J., RUDWALEIT, M., SIEPER, J., SAMPAIO-BARROS, P., WIEK, D. & BRAUN, J. 2017. 2016 update of the ASAS-EULAR management recommendations for axial spondyloarthritis. Annals of the Rheumatic Diseases, 76, 978-991.
VAN DER LINDEN, S., VALKENBURG, H. A. & CATS, A. 1984a. Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York criteria. Arthritis Rheum, 27, 361-8.
VAN DER LINDEN, S. M., VALKENBURG, H. A., DE JONGH, B. M. & CATS, A. 1984b. The risk of developing ankylosing spondylitis in HLA-B27 positive individuals. A comparison of relatives of spondylitis patients with the general population. Arthritis Rheum, 27, 241-9.
VAN PRAET, L., JANS, L., CARRON, P., JACQUES, P., GLORIEUS, E., COLMAN, R., CYPERS, H., MIELANTS, H., DE VOS, M., CUVELIER, C., VAN DEN BOSCH, F. & ELEWAUT, D. 2014. Degree of bone marrow oedema in sacroiliac joints of patients with axial spondyloarthritis is linked to gut inflammation and male sex: results from the GIANT cohort. Ann Rheum Dis, 73, 1186-9.
VERMA, R. P. & HANSCH, C. 2007. Matrix metalloproteinases (MMPs): chemical-biological functions and (Q)SARs. Bioorg Med Chem, 15, 2223-68.
WANG, R., GABRIEL, S. E., WARD, M. M. 2016. Progression of Nonradiographic Axial Spondyloarthritis to Ankylosing Spondylitis: A Population-Based Cohort Study. Arthritis Rheumatol, 68, 1415-21.
WEBER, U., LAMBERT, R. G., PEDERSEN, S. J., HODLER, J., OSTERGAARD, M. & MAKSYMOWYCH, W. P. 2010. Assessment of structural lesions in sacroiliac joints enhances diagnostic utility of magnetic resonance imaging in early spondylarthritis. Arthritis Care Res (Hoboken), 62, 1763-71.
WEBER, U., PEDERSEN, S. J., ØSTERGAARD, M., RUFIBACH, K., LAMBERT, R. G. W. & MAKSYMOWYCH, W. P. 2012. Can erosions on MRI of the sacroiliac joints be reliably detected in patients with ankylosing spondylitis? - A cross-sectional study. Arthritis Research & Therapy, 14, R124-R124.
WEI, J. C., TSAI, W. C., LIN, H. S., TSAI, C. Y. & CHOU, C. T. 2004. HLA-B60 and B61 are strongly associated with ankylosing spondylitis in HLA-B27-negative Taiwan Chinese patients. Rheumatology (Oxford), 43, 839-42.
XIE, W., ZHOU, L., LI, S., HUI, T. & CHEN, D. 2016a. Wnt/β-catenin signaling plays a key role in the development of spondyloarthritis. Annals of the New York Academy of Sciences, 1364, 25-31.
XIE, Z., WANG, P., LI, Y., DENG, W., ZHANG, X., SU, H., LI, D., WU, Y. & SHEN, H. 2016b. Imbalance Between Bone Morphogenetic Protein 2 and Noggin Induces Abnormal Osteogenic Differentiation of Mesenchymal Stem Cells in Ankylosing Spondylitis. Arthritis Rheumatol, 68, 430-40.
YANG, C., GU, J., RIHL, M., BAETEN, D., HUANG, F., ZHAO, M., ZHANG, H., MAKSYMOWYCH, W. P., DE KEYSER, F., VEYS, E. M. & YU, D. T. 2004. Serum levels of matrix metalloproteinase 3 and macrophage colony-stimulating factor 1 correlate with disease activity in ankylosing spondylitis. Arthritis Rheum, 51, 691-9.
YANG, J., ZHANG, X., MA, Y., WU, M., HU, X., HAN, R., YUAN, Y., WANG, M., CHEN, M., JIANG, S., TONG, J., XU, S., XU, J., SHUAI, Z., ZOU, Y. & PAN, F. 2017. Serum levels of leptin, adiponectin and resistin in patients with ankylosing spondylitis: A systematic review and meta-analysis. Int Immunopharmacol, 52, 310-317.
YU, Y., LIU, Y., SHI, F. D., ZOU, H., MATARESE, G. & LA CAVA, A. 2013. Cutting edge: Leptin-induced RORgammat expression in CD4+ T cells promotes Th17 responses in systemic lupus erythematosus. J Immunol, 190, 3054-8.
ZÁVADA, J., UHER, M., SVOBODOVÁ, R., OLEJÁROVÁ, M., HUŠÁKOVÁ, M., CIFERSKÁ, H., HULEJOVÁ, H., TOMČÍK, M., ŠENOLT, L. & VENCOVSKÝ, J. 2015. Serum tenascin-C discriminates patients with active SLE from inactive patients and healthy controls and predicts the need to escalate immunosuppressive therapy: a cohort study. Arthritis Research & Therapy, 17, 341.
ZHANG, L., LI, Y. G., LI, Y. H., QI, L., LIU, X. G., YUAN, C. Z., HU, N. W., MA, D. X., LI, Z. F., YANG, Q., LI, W. & LI, J. M. 2012. Increased frequencies of Th22 cells as well as Th17 cells in the peripheral blood of patients with ankylosing spondylitis and rheumatoid arthritis. PLoS One, 7, e31000.
Předběžná náplň práce
Axiální spondyloartritidy (axSpA) patří mezi chronická zánětlivá revmatická onemocnění postihující primárně páteř a její přilehlé struktury. Pro onemocnění jsou charakteristické nejen destruktivní kloubní změny ale zejména nadměrná osteoprodukce, která může vézt k postupné ankylóze páteře, a tím významně omezit mobilitu a kvalitu života pacientů. Patogeneze onemocnění není dosud plně objasněna, avšak předpokládá se silný genetický podklad spolu s dysregulací tkáňového metabolismu vznikající na podkladě nerovnováhy pro a protizánětlivých imunitních mechanismů. Doposud nebyl identifikován biomarker, který by pomohl při časné diagnostice, monitoraci aktivity subchondrálního postižení a diferenciaci rychleji progredujících pacientů. Cílem práce bylo zjistit hladiny potenciálních biomarkerů vycházejících z metabolismu pojivových tkání, tukového metabolismu a nových slibných biomarkerů a to pro oba podtypy onemocnění, jejich vztah k aktivitě nemoci a progresivním radiografickým změnám.
Prokázali jsme zvýšené sérové (případě plasmatické) hladiny biomarkerů metabolismu pojiva, konkrétně degradačních produktů metaloproteináz, které byly schopny diferencovat pacienty s časnou i pozdní formou nemoci od zdravých jedinců, měly vztah k aktivitě a radiografické progresi nemoci. Dále jsme prokázali vztah adipokinů k axSpA, kdy byly konkrétně sérové hodnoty visfatinu významně vyšší u pacientů s axSpA oproti ZK, a dále byly asociovány s radiografickým postižením páteře. Jako první jsme publikovali práci zabývající se možným vztahem microRNA k patogenezi a progresi onemocnění a v neposlední řadě jsme prokázali vyšší plasmatické hladiny proteinu tepelného šoku 90 (heat shock protein - Hsp) u pacientů s oběma formami nemoci a jeho asociaci s prvními subchondrálními změnami charakteru kostního edému na magnetické rezonanci.
Výsledky našich studií podpořily předchozí nálezy o dysregulaci metabolismu pojivových a tukové tkáně a ukázaly na možnou asociaci se subchondrálním poškozením u časné i pozdní formy axSpA. Navíc jsme poukázali na nové, ještě nedostatečně prozkoumané biomarkery, které by mohly vnést další světlo do složité patogeneze onemocnění.
Předběžná náplň práce v anglickém jazyce
Axial spondyloarthritis (axSpA) is a chronic inflammatory rheumatic disease affecting primarily the spine and its adjacent structures. The disease is characterized not only by destructive joint changes but also by excessive osteoproduction, which can lead to gradual ankylosis of the spine and thus significantly reduce the mobility and quality of life. The pathogenesis of the disease is not yet fully understood, but a strong genetic background is suggested, along with dysregulation of tissue metabolism resulting from an imbalance of pro- and anti-inflammatory immune mechanisms. We are still lacking biomarker with sufficient sensitivity and specificity which could help to identify early diagnosis, to monitor subchondral damage, and to differentiate rapidly progressing patients. The aim of this work was to determine the levels of potential biomarkers of connective tissue metabolism, fat metabolism and new promising biomarkers for both disease subtypes, their relationship to disease activity and progressive structural changes.
We have shown increased serum/plasma levels of connective tissue metabolism biomarkers (especially matrix metalloproteinase mediated metabolites), which were able to differentiate patients with early and late forms of axSpA from healthy individuals (HC), were related to disease activity and radiographic progression. Furthermore, we demonstrated the relationship between adipokines and axSpA patients. Specifically, visfatin serum levels were significantly higher in axSpA patients compared to HC and were associated with spinal involvement. We were the first to report the possible relationship between microRNA in pathogenesis of the disease and its progression. Furthermore, we presented higher plasma levels of heat shock protein 90 (Hsp90) in patients with both forms of disease and their association to the primary subchondral changes in a form of bone edema.
The results of our studies support recent findings of dysregulation in connective and adipose tissue metabolism and showed a possible association with subchondral damage of early and late forms of axSpA. In addition, we pointed out new, yet not fully studied biomarkers that could bring additional information into the complex pathogenesis of the axSpA.
 
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