Anti-cyclic citrullinated peptide antibody isotypes in rheumatoid arthritis : association with disease duration, rheumatoid factor production and the presence of shared epitope

• Published in: Clinical and experimental rheumatology Vol. 26; no. 2; pp. 253 - 260
• Main Authors: LAKOS, G, SOOS, L, SZEKANECZ, Z, FEKETE, A, SZABO, Z, ZEHER, M, HORVATH, I. F, DANKO, K, KAPITANY, A, GYETVAI, A, SZEGEDI, G
• Format: Journal Article
• Language: English
• Published: Pisa Clinical and Experimental Rheumatology 01-03-2008
• Subjects: Adult; Aged; Arthritis, Rheumatoid - epidemiology; Arthritis, Rheumatoid - genetics; Arthritis, Rheumatoid - immunology; Autoantibodies - blood; Autoantibodies - immunology; Biological and medical sciences; Diseases of the osteoarticular system; Epitopes - genetics; Epitopes - immunology; Female; Genotype; HLA-DR Antigens - genetics; HLA-DRB1 Chains; Humans; Immunoglobulin A - blood; Immunoglobulin A - immunology; Immunoglobulin G - blood; Immunoglobulin G - immunology; Immunoglobulin M - blood; Immunoglobulin M - immunology; Inflammatory joint diseases; Male; Medical sciences; Middle Aged; Peptides, Cyclic - immunology; Rheumatoid Factor - blood; Rheumatoid Factor - immunology; Seroepidemiologic Studies; Severity of Illness Index; Immunopathology; IgA; Antigenic determinant; Peptides; Antibody; anti-CCP2; Diseases of the osteoarticular system; Rheumatology; Autoimmune disease; Isotype; Inflammatory joint disease; Duration; IgM; Rheumatoid factor; Chronic; Rheumatoid arthritis; Production; duration of RA
• ISSN: 0392-856X; 1593-098X

Anti-cyclic citrullinated peptide (anti-CCP) antibodies of IgG isotype are specific diagnostic markers of rheumatoid arthritis (RA). Recent evidence also points to their direct involvement in the pathophysiology. Little information is available, however, regarding the isotype distribution of anti-CCP antibodies and the characteristics of IgA and IgM anti-CCP.
IgG, IgA and IgM anti-CCP2 and rheumatoid factor (RF) levels were measured in the sera of 119 RA patients and 118 controls, including patients with other rheumatic diseases and healthy subjects. We analyzed the diagnostic performance of IgA and IgM anti-CCP2 antibodies and their relationship with IgG anti-CCP2, RFs, disease duration and the presence of HLA-DRB1 shared epitope (SE) alleles.
Patients with RA had significantly higher serum IgA and IgM anti-CCP2 antibody levels than healthy subjects and patients with other rheumatic diseases (p<0.0001). IgG, IgA and IgM anti-CCP2 antibodies were present in 74.8%, 52.9% and 44.5% of RA patients, and their diagnostic specificity was 95.8%, 95.8% and 91.6%, respectively. The presence of anti-CCP2 antibodies was significantly associated with SE alleles (p=0.03). The frequency of IgM anti-CCP2 positivity was lower in longstanding disease compared to early RA (p=0.03).
IgA and IgM anti-CCP2 antibodies are present in RA patients, and they are similarly specific for RA as IgG anti-CCP2. The higher frequency of IgM anti-CCP2 antibodies in early RA suggests that they are mostly generated during the first phase of immune response; nonetheless, their production seems to be sustained in some patients. Further analysis of IgM and IgA anti-CCP2 antibodies may provide insights into the pathogenesis of RA.