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Objective First-degree relatives (FDRs) of rheumatoid arthritis (RA) patients sharing genetic and environmental risk factors for RA may represent a pre-RA state. Since anti–cyclic citrullinated protein/peptide antibodies (ACPAs) appear years before the onset of RA, the purpose of this study was to determine the prevalence of various ACPAs in FDRs of RA patients. Methods We evaluated 88 RA patients, 50 unaffected FDRs, and 20 healthy control subjects. Six different types of ACPAs were determined by enzyme-linked immunosorbent assay. Joint and periodontal disease symptoms were self-reported. Patients and FDRs were HLA typed for the shared epitope (SE) and the RA-protective alleles HLA–DRB*1301/1302. Results FDRs had a high prevalence of ACPAs (48%) as compared to controls (10%). Prevalence of the SE and smoking in FDRs was also high (62% and 49%, respectively). Of all of the ACPAs in the FDRs, 13 of 32 (41%) were of the IgA isotype. The most commonly expressed IgG ACPA targeted citrullinated vimentin, occurring in 20% of FDRs. The FDRs had an average of 1 type of ACPA, whereas the RA patients expressed a median of 5 different ACPAs. The only FDR to later develop RA expressed 4 different ACPAs. Joint and periodontal disease symptoms in the FDRs were significantly associated with smoking (OR 5.714 [95% confidence interval (95% CI) 1.151–28.3] and OR 12.25 [95% CI 2.544–58.99], respectively), but not with ACPAs. Conclusion The rate of ACPA positivity in unaffected FDRs of RA patients with a high prevalence of the SE and smoking was 48%, whereas ACPAs were rare in the healthy controls. ACPAs in the FDRs of RA patients was most commonly of the IgA isotype, but IgG ACPA targeting citrullinated vimentin was also frequently found.

Objective. To assess the role of T cells in the mouse model of citrullinated human fibrinogen - induced rheumatoid arthritis (RA) using CTLA-4Ig, an agent that blocks T cell costimulation, which is required for T cell activation. Methods. Humanized HLA-DRβ1*0401 - transgenic (DR4-Tg) mice were immunized with Cit - human fibrinogen to induce arthritis. Prior to, and at the onset or peak of, arthritis, the DR4-Tg mice were treated with CTLA-4Ig or control human IgG1 or were left untreated. Arthritis development and progression were monitored by measuring ankle swelling with calipers and by assessing histopathologic changes. The immune responses to the citrullinated antigens and the corresponding unmodified antigens, as well as the arthritogenicity of lymphocytes from these mice, were examined. The latter was performed using lymphocyte transfers from CTLA-4Ig - treated or control mice via intraperitoneal injection into naive DR4-Tg mice. Recipient mice also received an intraarticular injection of Cit - human fibrinogen, unmodified human fibrinogen, or vehicle. Results. CTLA-4Ig - treated, but not human IgG1-treated, arthritic mice had significantly reduced ankle swelling and pathologic joint damage. Treatment with CTLA-4Ig, but not human IgG1, suppressed Cit - human fibrinogen - induced T cell activation, including citrulline-specific T cell activation, when given prior to disease onset. Transfer of splenic lymphocytes from untreated or human IgG1 - treated arthritic mice caused arthritis in recipients, and this occurred when Cit - human fibrinogen, but not unmodified fibrinogen, was deposited into the joint. Splenocytes from CTLA-4Ig - treated mice were unable to transfer arthritis. Conclusion. Activated citrulline-specific T cells play a direct role in the development and progression of arthritis in this model of Cit-human fibrinogen-induced RA. © 2010, American College of Rheumatology.

The ability of monoclonal IgM anti‐DNA auto‐antibodies derived from normal human lymphoid cells to bind to cellular constituents of human epithelial cells (HEp‐2) was examined by immunofluorescence. Hybridoma supernatants from 10 different clones were studied. Four of them gave a strong fibrillar cytoplasmic staining that resembled cytoskeletal staining, 1 showed strong nuclear staining only, 3 showed weak nucleolar staining only, and 2 showed no staining. The hybridoma supernatants that reacted with HEp‐2 cytoskeleton were either polyspecific for various nucleic acid antigens, such as single‐stranded DNA, DNA, poly(dA:dT), poly(dG)·poly(dC), RNA, and cardiolipin, or were restricted to cardiolipin. Cytoskeletal staining identical to the hybridoma supernatant staining was also seen with mouse monoclonal anti‐vimentin antibody B11.5.1. Inhibition of the cytoskeletal staining was accomplished in 3 of the 4 hybridoma supernatants by preabsorption of these hybridoma supernatants with cardiolipin and/or single‐stranded DNA, or by preincubation of the HEp‐2 cells with the mouse monoclonal anti‐vimentin antibody. Copyright © 1986 American College of Rheumatology