1. Determination of Autoantibody Isotypes Increases the Sensitivity of Serodiagnostics in Rheumatoid Arthritis
- Author
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Farideh Alasti, Thomas Horn, S Swiniarski, Stephan Blüml, Maresa Grundhuber, Alexander Platzer, Helmuth Haslacher, Josef S Smolen, Daniela Sieghart, Paul Studenic, and Günter Steiner
- Subjects
Male ,0301 basic medicine ,rheumatoid arthritis ,lcsh:Immunologic diseases. Allergy ,autoantibodies ,Immunology ,Sensitivity and Specificity ,Serology ,rheumatoid factor ,Arthritis, Rheumatoid ,03 medical and health sciences ,0302 clinical medicine ,Antibody Specificity ,Humans ,Immunology and Allergy ,Rheumatoid factor ,Medicine ,Serologic Tests ,immunoglobulin isotypes ,anti-citrullinated protein antibodies ,Original Research ,Aged ,030203 arthritis & rheumatology ,biology ,Diagnostic Tests, Routine ,business.industry ,Autoantibody ,Anti–citrullinated protein antibody ,Middle Aged ,Isotype ,Healthy Volunteers ,3. Good health ,030104 developmental biology ,Case-Control Studies ,biology.protein ,Female ,RA33 ,Antibody ,business ,lcsh:RC581-607 ,Nephelometry ,RA33 antibodies - Abstract
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.
- Published
- 2018