Determination of Autoantibody Isotypes Increases the Sensitivity of Serodiagnostics in Rheumatoid Arthritis

• Published in: Frontiers in Immunology Vol. 9; p. 876
• Main Authors: Sieghart, Daniela, Platzer, Alexander, Studenic, Paul, Alasti, Farideh, Grundhuber, Maresa, Swiniarski, Sascha, Horn, Thomas, Haslacher, Helmuth, Blüml, Stephan, Smolen, Josef, Steiner, Günter
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media SA 24.04.2018; Frontiers Media S.A
• Subjects: Aged; Anti-Citrullinated Protein Antibodies; Anti-Citrullinated Protein Antibodies - blood; Anti-Citrullinated Protein Antibodies - immunology; Antibody Specificity; Antibody Specificity - immunology; Arthritis, Rheumatoid; Arthritis, Rheumatoid - blood; Arthritis, Rheumatoid - diagnosis; Arthritis, Rheumatoid - immunology; autoantibodies; Case-Control Studies; Diagnostic Tests, Routine; Diagnostic Tests, Routine - methods; Female; Healthy Volunteers; Humans; immunoglobulin isotypes; Immunoglobulin Isotypes - blood; Immunoglobulin Isotypes - immunology; Immunologic diseases. Allergy; Immunology; Male; Middle Aged; RA33 antibodies; RC581-607; rheumatoid arthritis; rheumatoid factor; Rheumatoid Factor - blood; Rheumatoid Factor - immunology; Sensitivity and Specificity; Serologic Tests; Serologic Tests - methods; anti-citrullinated protein antibodies; autoantibodies; rheumatoid arthritis; RA33 antibodies; rheumatoid factor; immunoglobulin isotypes
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2018.00876

Anti-citrullinated protein antibodies (ACPA) and rheumatoid factor (RF) are the most commonly used diagnostic markers of rheumatoid arthritis (RA). These antibodies are predominantly of the immunoglobulin (Ig) M (RF) or IgG (ACPA) isotype. Other subtypes of both antibodies-particularly IgA isotypes and other autoantibodies-such as RA33 antibodies-have been repeatedly reported but their diagnostic value has still not been fully elucidated. Here, we investigated the prevalence of IgA, IgG, and IgM subtypes of RF, ACPA, and RA33 antibodies in patients with RA. To determine the diagnostic specificity and sensitivity sera from 290 RA patients (165 early and 125 established disease), 261 disease controls and 100 healthy subjects were tested for the presence of IgA, IgG, and IgM isotypes of RF, ACPA, and RA33 by EliA™ platform (Phadia AB, Uppsala, Sweden). The most specific antibodies were IgG-ACPA, IgA-ACPA, and IgG-RF showing specificities >98%, closely followed by IgG- and IgA-RA33 while IgM subtypes were somewhat less specific, ranging from 95.8% (RA33) to 90% (RF). On the other hand, IgM-RF was the most sensitive subtype (65%) followed by IgG-ACPA (59.5%) and IgA-RF (50.7%). Other subtypes were less sensitive ranging from 35 (IgA-ACPA) to 6% (IgA-RA33). RA33 antibodies as well as IgA-RF and IgA-ACPA were found to increase the diagnostic sensitivity of serological testing since they were detected also in seronegative patients reducing their number from 109 to 85. Moreover, analyzing IgM-RF by EliA™ proved more sensitive than measuring RF by nephelometry and further reduced the number of seronegative patients to 76 individuals. Importantly, among antibody positive individuals, RA patients were found having significantly more antibodies (≥3) than disease controls which generally showed one or two antibody species. Thus, increasing the number of autoantibodies in serological routine testing provides valuable additional information allowing to better distinguish between RA and other rheumatic disorders, also in patients not showing antibodies in current routine diagnostics. In conclusion, testing for multiple autoantibody specificities increases the diagnostic power of autoimmune diagnostics and could further support physicians in clinical decision-making.