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Expansion of Alternative Autoantibodies Does Not Follow the Evolution of Anti–Citrullinated Protein Antibodies in Preclinical Rheumatoid Arthritis: An Analysis in At‐Risk First Degree Relatives
Author(s) -
Anaparti Vidyanand,
Smolik Irene,
Meng Xiaobo,
O’Neil Liam,
Jantz Mackenzie A.,
Fritzler Marvin J.,
ElGabalawy Hani
Publication year - 2021
Publication title -
arthritis and rheumatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.106
H-Index - 314
eISSN - 2326-5205
pISSN - 2326-5191
DOI - 10.1002/art.41675
Subject(s) - autoantibody , rheumatoid arthritis , medicine , rheumatoid factor , immunology , first degree relatives , cohort , antibody , citrullination , autoimmunity , rheumatology , anti nuclear antibody , arthritis , autoimmune disease , biology , family history , biochemistry , citrulline , arginine , amino acid
Objective Co‐occurrence of autoantibodies specific for ≥1 autoimmune disease is widely prevalent in rheumatoid arthritis (RA) patients. To understand the prevalence of polyautoimmunity in preclinical RA, we performed a comprehensive autoantibody assessment in a First Nations cohort of at‐risk first‐degree relatives (FDR) of RA patients, a subset of whom subsequently developed RA (progressors). Methods Venous blood was collected from all study participants (n = 50 RA patients and 64 FDR) at scheduled visits, and serum was stored at −20°C. High‐sensitivity C‐reactive protein level, anti–citrullinated protein antibody (ACPA) status, and autoantibody status were determined using commercially available enzyme‐linked immunosorbent assay kits. Rheumatoid factor (RF) was detected by nephelometry. Antinuclear autoantibodies (ANA) were identified using Hep‐2 indirect immunofluorescence assay (IFA) and classified according to international consensus nomenclature as various anti‐cell (AC) patterns. Results Of our study cohort, 78.9% had positive ANA reactivity (≥1:80), which was either a homogenous, fine‐speckled (AC‐1 and AC‐4) or mixed IFA pattern. Importantly, the AC‐4 and mixed ANA patterns were also observed in progressors at the time of disease onset. While all of the RA patients showed a high prevalence of arthritis‐associated autoantibodies, they also had a high prevalence of extractable nuclear antigen–positive autoantibodies to other autoantigens. In FDR, we did not observe any increase in serum autoreactivity to nonarthritis autoantigens, either cross‐sectionally or in samples collected longitudinally from progressors prior to RA onset. Conclusion While alternative autoimmunity and ANA positivity are widely prevalent in First Nations populations, including asymptomatic, seronegative FDR, expansion of alternative autoimmunity does not occur in parallel with ACPA expansion in FDR and is restricted to patients with established RA.