Changes in anti-citrullinated protein antibody isotype levels in relation to disease activity and response to treatment in early rheumatoid arthritis. (14th October 2018)

• Record Type: Journal Article
• Authors: Kastbom, A; Roos Ljungberg, K; Ziegelasch, M; Wetterö, J; Skogh, T; Martinsson, K
• Is Part Of: Clinical and experimental immunology. Volume 194:Number 3(2018:Dec.)
• Page Start: 391
• Page End: 399
• Publication Date: 2018-10-14
• Subjects: anti-citrullinated protein antibodies (ACPA) -- disease course -- immunoglobulin (Ig) isotypes -- longitudinal analyses -- rheumatoid arthritis (RA); Immunopathology -- Periodicals; 616.079
• DOI: 10.1111/cei.13206
• Languages: English
• ISSNs: 0009-9104

Abstract

Summary: Rheumatoid arthritis (RA) is a chronic inflammatory disease where serum analysis of anti-citrullinated peptide/protein antibodies (ACPA) is an important diagnostic/prognostic tool. Levels and changes of ACPA in RA patients have been studied previously in relation to disease course and therapy response, but less is known regarding ACPA isotype changes in early RA. Hence, recent-onset RA patients ( n = 231) were subjected to a 3-year clinical and radiological follow-up. Serum samples were serially collected and ACPA isotypes were analysed using the second-generation cyclic citrullinated peptide (CCP) as capture antigen. Changes in ACPA isotype levels and status were related to disease course and pharmacotherapy. At inclusion, 74% of the patients tested positive for ACPA IgG; 55% for immunoglobulin (Ig)A, 37% for secretory IgA (SIgA) and 35% for IgM. The proportion of positive patients decreased significantly at follow-up regarding ACPA SIgA, IgM and IgA. During the initial 3 months, reduction of the 28-joint disease activity score (DAS28) correlated with reduced levels of ACPA IgG (Rho = 0·242, P = 0·003), IgA (Rho = 0·260, P = 0·008), IgM (Rho = 0·457, P < 0·001) and SIgA (Rho = 0·402, P < 0·001). Levels of ACPA SIgA ( P = 0·008) and IgM ( P = 0·021) decreased significantly among patients with good response to treatment, which was not seen regarding ACPA IgA or IgG. Changes in ACPA isotype levels were not associated with radiographic damage. In conclusion, ACPA SIgA and IgM declined rapidly upon anti-rheumatic therapy and correlated with decreased disease activity in recent-onset RA. This may indicate that down-regulation of mucosal immunity to citrullinated proteins/peptides and recruitment of new B cells are key features of therapy responses in early RA. Graphical Abstract: