Rheumatoid Arthritis

Rheumatoid arthritis is a quintessential immune-mediated disease with chronic smoldering immune responses in the joints that cause irreversible damage to cartilage and bone. The syndrome is systemic in nature, but synovitis of the diathrodial joints is the most visible manifestation. Although the therapeutic management of patients with RA has seen a major evolution with the introduction of biological reagents, our understanding of the disease is still rudimentary. Researchers in the Lowance Center are working to explain the targeting of abnormal immune responses to the synovial space by studying unique structural elements of the synovial microenvironment and by identifying molecular targets that govern the interaction between T cells and synovial fibroblasts. A second major area of research is based on the clinical finding that rheumatoid arthritis is a disease of the elderly, not of the young. Ongoing studies examine the contribution of immunosenescence to derailing immune tolerance. These studies have the potential of developing new therapeutic strategies that repair—instead of inhibit—the immune system.

Publications

Weyand CM, Goronzy JJ. T-cell targeted therapies in rheumatoid arthritis. Nat Clin Pract Rheum 2:201-210, 2006.

Weyand CM, Goronzy JJ, Kurtin PJ. Lymphoma in rheumatoid arthritis – An immune system set up for failure. Arthritis Rheum 54:685-689, 2006.

Weyand CM, Goronzy JJ. Pathomechanisms in rheumatoid arthritis – Time for a “string” theory? J Clin .Invest 116:869-871, 2006.

Sawai H, Park YW, Roberson J, Imai T, Goronzy JJ, Weyand CM. T cell costimulation by fractalkine-expressing synoviocytes in rheumatoid arthritis. Arthritis Rheum 52:1392-1401, 2005.

Davila E, Kang YM, Park YW, Sawai H, Xe H, Pryshchep S, Goronzy JJ, Weyand CM. Cell-based immunotherapy with suppressor CD8 + T cells in rheumatoid arthritis. J Immunol 174:7292-7301, 2005.

Warrington KJ, Kent PD, Frye RL, Lymp JF, Kopecky SL, Goronzy JJ, Weyand CM. Rheumatoid arthritis is an independent risk factor for multi-vessel coronary artery disease: a case control study. Arthritis Res Ther 7:R984-R991, 2005.

Seyler TM, Park YW, Takemura S, Bram RJ, Kurtin PJ, Goronzy JJ, Weyand CM. BLyS and APRIL in rheumatoid arthritis . J Clin Invest 115:3083-3092, 2005.

Zhang X, Nakajima T, Goronzy JJ, Weyand CM. Tissue trafficking patterns of effector memory CD4 + T cells in rheumatoid arthritis. Arthrithis Rheum 52:3839-3849, 2005.

Goronzy JJ , Weyand CM. Rheumatoid arthritis. Immunol Rev 204:55-73, 2005.

Weyand CM, Seyler TM, Goronzy JJ. B cells in rheumatoid synovitis. Arthritis Res Ther 7(Suppl 3):S9-S12, 2005.

Park YW, Pryshchep S, Goronzy JJ, Weyand CM. B cells as a therapeutic target in autoimmune diseases. Expert Opin Ther Targets 9:431-445, 2005.

Goronzy JJ , Henel G, Sawai H, Singh K, Lee EB, Pryshchep S, Weyand CM. Costimulatory pathways in rheumatoid synovitis and T-cell senescence. Ann NY Acad Sci 1062:182-195, 2005.

Goronzy JJ , Matteson EL, Fulbright JW, Warrington KJ, Chang-Miller A, Hunder GG, Mason TG, Nelson AM, Valente RM, Crowson CS, Erlich HA, Reynolds RL, Swee RG, O’Fallon WM, Weyand CM. Prognostic markers of radiographic progression in early rheumatoid arthritis. Arthritis Rheum 50:43-54, 2004.

Matteson EL, Weyand CM, Fulbright JW, Christianson TJH, McClelland RL, Goronzy JJ. How aggressive should initial therapy for rheumatoid arthritis be? Factors associated with response to ‘non-aggressive’ DMARD treatment and perspective from a 2-yr open label trial. Rheumatology 43:619-625, 2004.

Braun A, Takemura S, Vallejo AN, Goronzy JJ, Weyand CM. Lymphotoxin-β–mediated stimulation of synoviocytes in rheumatoid arthritis. Arthritis Rheum 50:2140-2150, 2004.

Park YW, Kang YM, Butterfield J, Detmar M, Goronzy JJ, Weyand CM. Thrombospondin 2 functions as an endogenous regulator of angiogenesis and autoimmunity in rheumatoid arthritis. Am J Pathol 165:2087-2098, 2004.

Goronzy JJ, Weyand CM. T-cell regulation in rheumatoid arthritis. Curr Opin Rheumatol 16:212-217, 2004.

Weyand CM, Goronzy JJ. Stem cell aging and autoimmunity in rheumatoid arthritis. Trends Mol Med 10:426-433, 2004.

Goronzy JJ, Weyand CM. B cells as a therapeutic target in autoimmune disease. Arthritis Res Ther 5:131-135, 2003.

Schönland SO, Lopez C, Widmann T, Zimmer J, Bryl E, Goronzy JJ, Weyand CM. Premature telomeric loss in rheumatoid arthritis is genetically determined and involves lymphoid and myeloid cell lineages. Proc Natl Acad Sci USA 100:13471-13476, 2003.

Weyand CM, Goronzy JJ. Ectopic germinal center formation in rheumatoid synovitis. Ann NY Acad Sci 987:140-149, 2003.

Weyand CM, Kang YM, Kurtin PJ, Goronzy JJ. The power of the third dimension: tissue architecture and autoimmunity in rheumatoid arthritis. Curr Opin Rheumatol 15(3):259-266, 2003.

Weyand CM, Fulbright JW, Goronzy JJ. Immunosenescence, autoimmunity, and rheumatoid arthritis. Exp Gerontol 38:833-841, 2003.

Goronzy JJ, Weyand CM. Ageing, autoimmunity and arthritis: T-cell senescence and contraction of T-cell repertoire diversity - catalysts of autoimmunity and chronic inflammation. Arthritis Res Ther 5:225-234, 2003.

Weyand CM, Goronzy JJ. Premature immunosenescence in rheumatoid arthritis. J Rheumatol 29:1141-1146, 2002.

Kang YM, Zhang X, Wagner UG, Yang H, Beckenbaugh RD, Kurtin PJ, Goronzy JJ, Weyand CM. CD8 T cells are required for the formation of ectopic germinal centers in rheumatoid synovitis. J Exp Med 195:1325-1336, 2002.

Goronzy JJ, Weyand CM. Thymic function and peripheral T-cell homeostasis in rheumatoid arthritis. Trends in Immunol 22:251-255, 2001.

Weyand CM, Kurtin PJ, Goronzy JJ. Ectopic lymphoid organogenesis-a fast track for autoimmunity. Am J Pathol 159:787-793, 2001.

Warrington KJ, Weyand CM, Goronzy JJ. Emerging insights into the cause of rheumatoid arthritis. J Musculoskel Med 18:459-472, 2001.

Warrington KJ, Takemura S, Goronzy JJ, Weyand CM. CD4+,CD28- T cells in rheumatoid arthritis patients combine features of the innate and adaptive immune systems. Arthritis Rheum 44:13-20, 2001.

Yen J-H, Moore BE, Nakajima T, Scholl D, Schaid DJ, Weyand CM, Goronzy JJ. Major histocompatibility complex class I-recognizing receptors are disease risk genes in rheumatoid arthritis. J Exp Med 193:1159-1167, 2001.

Takemura S, Braun A, Crowson C, Kurtin PJ, Cofield RH, O’Fallon WM, Goronzy JJ, Weyand CM. Lymphoid neogenesis in rheumatoid synovitis. J Immunol 167:1072-1080, 2001.

Takemura S, Klimiuk PA, Braun A, Goronzy JJ, Weyand CM. T cell activation in rheumatoid synovium is B cell dependent. J Immunol 167:4710-4718, 2001.

Weyand CM, Goronzy JJ. Association of MHC and rheumatoid arthritis: HLA polymorphisms in phenotypic variants of rheumatoid arthritis. Arthritis Res 2000, 2:212-216.

Namekawa T, Snyder MR, Yen JH, Goehring BE, Leibson PJ, Weyand CM, Goronzy JJ. Killer cell activating receptors function as costimulatory molecules on CD4+CD28null T cells clonally expanded in rheumatoid arthritis. J Immunol 165:1138-1145, 2000.

Koetz K, Bryl E, Spickschen K, O’Fallon WM, Goronzy JJ, Weyand CM. T cell homeostasis in patients with rheumatoid arthritis. Proc Natl Acad SciUSA 97:9203-9208, 2000.

Weyand CM, Goronzy JJ, Takemura S, Kurtin PJ. Cell-cell interactions in synovitis: Interactions between T cells and B cells in rheumatoid arthritis. Arthritis Res 2:457-463, 2000.

Weyand CM, Goronzy JJ. T-cell responses in rheumatoid arthritis: systemic abnormalities – local disease. Curr Opin Rheumatol 11(3):210-217, 1999.

Klimiuk PA, Yang H, Goronzy JJ, Weyand CM. Production of cytokines and metalloproteinases in rheumatoid synovitis is T cell dependent. Clin Immunol 90:65-78, 1999.

Klimiuk PA, Goronzy JJ, Weyand CM. IL-16 as an anti-inflammatory cytokine in rheumatoid synovitis. J Immunol 162:4293-4299, 1999.

Yang H, Rittner H, Weyand CM, Goronzy JJ. Aberrations in the primary T cell receptor repertoire as predisposition for synovial inflammation in rheumatoid arthritis. J Invest Med 47:236-245, 1999.

Weyand CM, Klimiuk PA, Goronzy JJ. Heterogeneity of Rheumatoid Arthritis: From Phenotypes to Genotypes. Springer Semin Immunopathol 20:5-22, 1998.

Weyand CM, Schmidt D, Wagner U, Goronzy JJ. The influence of sex on the phenotype of rheumatoid arthritis. Arthritis Rheum 41:817-822, 1998.

Wagner U, Kurtin P, Wahner A, Brackertz M, Berry D, Goronzy JJ, Weyand CM. The role of CD8+ CD40L+ T cells in the formation of germinal centers in rheumatoid synovitis. J Immunol 161:6390-6397, 1998.

Wagner UG, Koetz K, Weyand CM, Goronzy JJ. Perturbation of the T cell repertoire in rheumatoid arthritis. Proc Natl Acad Sci 95:14447-14452, 1998.

Weyand CM, Goronzy JJ. Pathogenesis of rheumatoid arthritis. Med Clin North Am 81:29-55, 1997.

Weyand CM, Goronzy JJ. The molecular basis of rheumatoid arthritis. J Mol Med 75:772-785, 1997.

Martens PB, Goronzy JJ, Schaid DJ, Weyand CM. Expansion of unusual CD4+ T cells in severe rheumatoid arthritis. Arthritis Rheum 40:1106-1114, 1997.

Rittner HL, Zettl A, Klimiuk P, Jendro MC, Bartz-Bazzanella P, Goronzy JJ, Weyand CM. Multiple mechanisms support oligoclonal T cell expansions in the rheumatoid synovium. Mol Med 3:452-465, 1997.

Klimiuk P, Goronzy JJ, Bjornsson J, Beckenbaugh RD, Weyand CM. Tissue cytokine patterns distinguish variants of rheumatoid synovitis. Am J Pathol 151:1311-1319, 1997.

Schmidt D, Goronzy JJ, Weyand CM. CD4+ CD7- CD28- T cells are expanded in rheumatoid arthritis and are characterized by autoreactivity. J Clin Invest 97:2027-2037, 1996.

Waase I, Kayser C, Carlson PJ, Goronzy JJ, Weyand CM. Oligoclonal T cell proliferation in patients with rheumatoid arthritis and their unaffected siblings. Arthritis Rheum 39:904-913, 1996.

Schmidt D, Martens PB, Weyand CM, Goronzy JJ. The repertoire of CD4+ CD28- T cells in rheumatoid arthritis. Mol Med 2:608-618, 1996.

Weyand CM, Goronzy JJ. Inherited and noninherited risk factors in rheumatoid arthritis. Curr Opin Rheumatol 7:206-213, 1995.

Goronzy JJ, Weyand CM. T and B cell dependent pathways in rheumatoid arthritis. Curr Opin Rheumatol 7:214-221, 1995.

Goronzy JJ, Weyand CM. T cells in rheumatoid arthritis-Paradigms and Facts. Rheum Dis Clin North Amer 21: 655-674, 1995.

Weyand CM, McCarthy TG, Goronzy JJ. Correlation between disease phenotype and genetic heterogeneity in rheumatoid arthritis. J Clin Invest 95:2120-2126, 1995.

Walser-Kuntz DR , Weyand CM, Weaver AJ, O’Fallon WM, Goronzy JJ. Mechanisms underlying the formation of the T cell receptor repertoire in rheumatoid arthritis. Immunity 2:597-605, 1995.

Jendro MC, Ganten T, Matteson E, Weyand CM, Goronzy JJ. Emergence of oligoclonal T cell populations following therapeutic T cell depletion in rheumatoid arthritis. Arthritis Rheum 38:1242-1251, 1995.

Goronzy JJ, Weyand CM. Vasculitis in rheumatoid arthritis. Curr Opin Rheumatol 6:290-294. 1994.

Goronzy JJ, Bartz-Bazzanella P, Hu W, Jendro MC, Walser-Kuntz DR, Weyand CM. Dominant clonotypes in the repertoire of peripheral CD4+ T cells in rheumatoid arthritis. J Clin Invest 94:2068-2076, 1994.

Weyand CM, Xie C, Goronzy JJ. Homozygosity for the HLA-DRB1 allele selects for extra-articular manifestations in rheumatoid arthritis. J Clin Invest 89:2033-2039, 1992.

Weyand CM, Hicok KC, Conn D, Goronzy JJ. The influence of HLA-DRB1 genes on disease severity in rheumatoid arthritis. Ann Intern Med 117:801-806, 1992.