Polyautoimmunity Clusters as a New Taxonomy of Autoimmune Diseases

Abstract

Polyautoimmunity (PolyA) is an emerging concept that may help to develop a better classification of autoimmune diseases (ADs). Thus, we aimed to develop new taxonomy based on PolyA. Two-hundred and fifty-four consecutive patients were included with rheumatoid arthritis (RA, n:146), systemic lupus erythematosus (SLE, n:45), Sjögrens syndrome (SS, n:29), autoimmune thyroid disease (AITD, n:17) and systemic sclerosis (SSc, n:17). Clinical features, autoantigen array chip, lymphocytes immunophenotype and cytokine profile were assessed simultaneously. The coexistence of two or more ADs with classification criteria was termed Overt PolyA, whereas the presence of autoantibodies unrelated to the index AD, without criteria fulfillment, was named Latent PolyA. Combination of IgG autoantibodies yielded high accuracy for classification of ADs. In SLE, Histone H2A, Sm/RNP, ssDNA, and dsDNA IgG autoantibodies were the most predictive autoantibodies for this condition. Laminin, Ro/SSA (52 kDa), and U1−snRNP B/B for SS; Thyroglobulin for AITD; Ribo Phosphoprotein P1, and CENP-A for SSc. Interestingly, Thyroglobulin and U1−snRNP B/B' were mutual diagnostic biomarkers in SS and SSc. Latent PolyA showed in nearly 70% of patients, whereas overt PolyA was most common in AITD (82.4%) and SLE (40%). Cluster analysis based on autoantibodies yielded three clusters of which clusters 2 and 3 exhibited high frequency of latent and overt PolyA with distinctive clinical and immunological phenotypes. Combination of autoantibodies demonstrated high performance for classification of ADs. Patients with both latent and overt PolyA cluster together and exhibit differential clinical and immunological features. High prevalence of latent and overt PolyA advocates for routinary surveillance in clinical settings.

Ocular Manifestations Related to Antibodies Positivity and Inflammatory Biomarkers in a Rheumatological Cohort

“…Rheumatological and autoimmune diseases are associated with multiple antibodies. 41 It has been described that some antibodies can predispose to polyautoimmunity, as is the case of Anti-Ro antibodies in SLE and ANAs antibodies in SS. 42 , 43 In 2001, Gilboe et al described that patients with poliautoimmunity (SLE and SS) and Anti-Ro/SSB antibodies presented worse outcomes on the visual analog fatigue scale (VAS).…”

Risk factors for developing Polyautoimmunity in patients with non-infectious uveitis and their impact on visual outcomes.

“…Latent PolyA was considered in patients with diagnosed IMDs who have autoantibodies unrelated to the index disease and do not ful ll diagnostic criteria for any additional IMDs 42,43 . Multiple autoimmune syndrome (MAS) was de ned as the coexistence of three or more different IMDs in one person 10 .…”