Background The anti-cyclic citrullinated peptide (CCP) antibody is a diagnostic biomarker of rheumatoid arthritis (RA). However, some non-RA connective tissue disease (CTD) patients also test... Show moreBackground The anti-cyclic citrullinated peptide (CCP) antibody is a diagnostic biomarker of rheumatoid arthritis (RA). However, some non-RA connective tissue disease (CTD) patients also test positive for the anti-CCP antibody and, thus, may ultimately develop RA. We retrospectively investigated whether anti-CCP-positive non-RA CTD patients developed RA and attempted to identify factors that may differentiate RA-overlapping CTD from pure CTD. Methods In total, 842 CTD patients with a primary diagnosis that was not RA were selected from our CTD database as of December 2012. Anti-CCP antibody titers were obtained from a retrospective chart review or measured using stored sera. RA was diagnosed according to the 1987 revised American College of Rheumatology classification criteria. Thirty-three anti-CCP-positive non-RA CTD patients were retrospectively followed up for the development of RA. Bone erosions on the hands and feet were assessed by X-ray. Citrullination dependency was evaluated by an in-house ELISA, the HLA-DRB1 allele was typed, and the results obtained were then compared between RA-overlapping and non-RA anti-CCP-positive CTD patients. Results Two out of 33 anti-CCP-positive CTD patients (6.1%) developed RA during a mean follow-up period of 8.9 years. X-rays were examined in 27 out of the 33 patients, and only one (3.7%) showed bone erosions. The frequency of the HLA-DRB1 shared epitope (SE) and anti-CCP antibody titers were both significantly higher in anti-CCP-positive RA-overlapping CTD patients than in anti-CCP-positive non-RA CTD patients, while no significant differences were observed in citrullination dependency. Conclusions Anti-CCP-positive non-RA CTD patients rarely developed RA. HLA-DRB1 SE and anti-CCP antibody titers may facilitate the differentiation of RA-overlapping CTD from anti-CCP-positive non-RA CTD. Show less
The scope of this thesis is to describe the immunological characteristics and molecular composition of anti-CarP antibodies in rheumatoid arthritis, as well as the presence of anti-CarP antibodies... Show moreThe scope of this thesis is to describe the immunological characteristics and molecular composition of anti-CarP antibodies in rheumatoid arthritis, as well as the presence of anti-CarP antibodies in relation to bone erosions on diseases other than RA. This thesis is subdivided in three parts.Part 1: Characterisation of the anti-CarP antibody response in rheumatoid arthritisBoth ACPA and anti-CarP antibodies are present in RA.We describe the examination of the anti-CarP antibody response in RA by means of isotype and IgG-subclass usage in baseline serum samples of RA-patients as well as by means of the avidity of anti-CarP antibodies. Moreover, the anti-CarP IgG V-domain glycosylation was studied.Part 2: Possibilities for a mucosal origin of autoantibodies in rheumatoid arthritisSeveral lines of evidence obtained in the recent years indicate a role for mucosal surfaces in the development of auto-immune responses associated with RA. Therefore, we studied the molecular composition of RA associated IgA autoantibodies.Part 3: anti-CarP antibodies in other rheumatic diseases that can be characterized by bone erosionsBecause anti-CarP antibodies and ACPAs are also present in other clinical conditions than RA, we investigated their presence and association with bone erosions in Systemic Lupus Erythematosus and hand osteorthritis. Show less
