Our findings suggest that the high level of cross reactivity amongst the RA autoreactive B cells is the result of different antigen encounters, possibly at different sites and at different time points. This is in line with the notion that RA is initiated in one context, such as in mucosal organs, and thereafter target other sites, such as joints. This article is protected by copyright. All rights reserved.

Conclusion. Development of an immune response toward citrullinated peptides is initially restricted but expands with time to induce a more specific response, with levels, particularly those of antibodies against CEP-1, Fib␤36-52, and filaggrin, increasing during the predating time period closer to the onset of symptoms.

The (111)In-DOTA-Z(EGFR:2377) Affibody molecule is a promising tracer for radionuclide molecular imaging of EGFR expression in malignant tumours. Careful optimization of protein dose is required for high-contrast imaging of EGFR expression in vivo.

ObjectiveFindings from previous studies have suggested that subclinical inflammation of the synovium does not coincide with the appearance of rheumatoid arthritis (RA)–specific autoantibodies. This study was undertaken to examine the relationship between the presence of autoantibodies, changes in the synovium, and development of arthritis over time in a markedly larger, prospective study.MethodsFifty-five individuals who were IgM rheumatoid factor positive and/or anti–citrullinated protein antibody (ACPA) positive (detected by the anti–cyclic citrullinated peptide antibody test) and who were without any evidence of arthritis upon physical examination were included in the study. ACPAs were subsequently also detected using a multiplex chip-based assay. All individuals underwent magnetic resonance imaging and mini-arthroscopic synovial biopsy sampling of a knee joint at inclusion and were prospectively followed up. Proportional hazards regression analysis was performed to investigate whether changes in the synovium were associated with the onset of arthritis.ResultsFifteen individuals (27%) developed arthritis after a median followup time of 13 months (interquartile range 6–27 months; range 1–47 months). No overt synovial inflammation was observed, but CD3+ T cell numbers in the biopsy tissue showed a borderline association with subsequent development of clinically manifest arthritis (hazard ratio 2.8, 95% confidence interval [95% CI] 0.9–9.1; P = 0.088). In addition, the presence of CD8+ T cells was associated with ACPA positivity (odds ratio [OR] 16.0, 95% CI 1.7–151.1) and with the total number of ACPAs present (OR 1.4, 95% CI 1.0–1.8).ConclusionThese findings confirm and extend previous results showing the absence of clearcut synovial inflammation in individuals having systemic autoimmunity associated with RA. However, subtle infiltration by synovial T cells may precede the signs and symptoms of arthritis in preclinical RA.