Type II Collagen Autoimmunity in Rheumatoid Arthritis

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Type II Collagen Autoimmunity in Rheumatoid Arthritis Wan-Uk Kim, MD, PHD, Mi-La Cho, PHD, Young Ok Jung, MD, So-Youn Min, PHD, Sung-Whan Park, MD, PHD, Do-Jun Min, MD, PHD, Jong-Hyun Yoon, MD, PHD, Ho-Youn Kim, MD, PHD  The American Journal of the Medical Sciences  Volume 327, Issue 4, Pages 202-211 (April 2004) DOI: 10.1097/00000441-200404000-00006 Copyright © 2004 Southern Society for Clinical Investigation Terms and Conditions

Figure 1 Presence of IgG anti-CII antibodies in human rheumatoid arthritis (RA). [Reprinted from Kim WU, Yoo WH, Park W, et al. IgG antibodies to type II collagen reflect inflammatory activity in patients with rheumatoid arthritis. J Rheumatol 2000;27:575–81. Copyright © 2000 Journal Of Rheumatology Publishing Co. Used with permission.] The American Journal of the Medical Sciences 2004 327, 202-211DOI: (10.1097/00000441-200404000-00006) Copyright © 2004 Southern Society for Clinical Investigation Terms and Conditions

Figure 2 High frequency of CII-reactive T cells and early stage of RA. [Reprinted from Kim HY, Kim WU, Cho ML et al. Enhanced T cell proliferative response to type II collagen and synthetic peptide CII (255–274) in patients with rheumatoid arthritis. Arthritis Rheum 1999;42:2085–93. Copyright © 1999 American College of Rheumatology. Used with permission.] The American Journal of the Medical Sciences 2004 327, 202-211DOI: (10.1097/00000441-200404000-00006) Copyright © 2004 Southern Society for Clinical Investigation Terms and Conditions

Figure 3 Increased production of Th1 cytokines by CII-stimulated synovial fluid mononuclear cells (SFMC) and peripheral blood mononuclear cells (PBMC) obtained from RA patients. [Reprinted from Park SH, Min DJ, Cho ML, et al. Shift toward T helper 1 cytokines by type II collagen-reactive T cells in patients with rheumatoid arthritis. Arthritis Rheum 2001;44:561–9. Copyright © 2001 American College of Rheumatology. Used with permission.] The American Journal of the Medical Sciences 2004 327, 202-211DOI: (10.1097/00000441-200404000-00006) Copyright © 2004 Southern Society for Clinical Investigation Terms and Conditions

Figure 4 Generation of CII/CII(255-274) specific T cell lines. The American Journal of the Medical Sciences 2004 327, 202-211DOI: (10.1097/00000441-200404000-00006) Copyright © 2004 Southern Society for Clinical Investigation Terms and Conditions

Figure 5 Positive selection of CII/CII (255-271) specific T cell clones. The American Journal of the Medical Sciences 2004 327, 202-211DOI: (10.1097/00000441-200404000-00006) Copyright © 2004 Southern Society for Clinical Investigation Terms and Conditions

Figure 6 Increasing interferon-γ (IFN-γ) production in accord to positive selection of CII-specific T cell clones in RA peripheral blood mononuclear cells (PBMC) (o). The concentration of IFN-γ according to the clonal expansion of CII (255-274)–reactive T cells in synovial fluid mononuclear cells (■) from RA patients and PBMC from health control subjects (Δ). The American Journal of the Medical Sciences 2004 327, 202-211DOI: (10.1097/00000441-200404000-00006) Copyright © 2004 Southern Society for Clinical Investigation Terms and Conditions

Figure 7 TCR analysis by RT-PCR-SSCP in RA. The American Journal of the Medical Sciences 2004 327, 202-211DOI: (10.1097/00000441-200404000-00006) Copyright © 2004 Southern Society for Clinical Investigation Terms and Conditions

Figure 8 TCR CDR3 analysis of CII specific T cells: Common band found on TCRVb14. The American Journal of the Medical Sciences 2004 327, 202-211DOI: (10.1097/00000441-200404000-00006) Copyright © 2004 Southern Society for Clinical Investigation Terms and Conditions

Figure 9 Induction of IL-15, IL-18, and TNF-α mRNA from fibroblast-like synoviocytes (FLS) after 24-hour co-culture. The American Journal of the Medical Sciences 2004 327, 202-211DOI: (10.1097/00000441-200404000-00006) Copyright © 2004 Southern Society for Clinical Investigation Terms and Conditions

Figure 10 RA synovial fibroblasts induce IL-15 and TNF-α production in a contact-dependent manner. The American Journal of the Medical Sciences 2004 327, 202-211DOI: (10.1097/00000441-200404000-00006) Copyright © 2004 Southern Society for Clinical Investigation Terms and Conditions

Figure 11 Chemokine production by interaction of CII-activated T cells with FLS. The American Journal of the Medical Sciences 2004 327, 202-211DOI: (10.1097/00000441-200404000-00006) Copyright © 2004 Southern Society for Clinical Investigation Terms and Conditions

Figure 12 Dependence of chemokine production on the duration that T cells was stimulated with CII. (A) FLS + T cells stimulated with CII for 5 days. (B) FLS + T cells stimulated with CII for 15 days. The American Journal of the Medical Sciences 2004 327, 202-211DOI: (10.1097/00000441-200404000-00006) Copyright © 2004 Southern Society for Clinical Investigation Terms and Conditions