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Autoantibodies to Disease-Related Proteins in Joints as Novel Biomarkers for the Diagnosis of Rheumatoid Arthritis

Authors :
Lönnblom, Erik
Leu Agelii, Monica
Sareila, Outi
Cheng, Lei
Xu, Bingze
Viljanen, Johan
Hafström, Ingiäld
Andersson, Maria L. E.
Bergström, Göran
Ekwall, Anna-Karin Hultgard
Rudin, Anna
Kastbom, Alf
Sjöwall, Christopher
Jacobsson, Lennart T. H.
Kihlberg, Jan
Gjertsson, Inger
Holmdahl, Rikard
Lönnblom, Erik
Leu Agelii, Monica
Sareila, Outi
Cheng, Lei
Xu, Bingze
Viljanen, Johan
Hafström, Ingiäld
Andersson, Maria L. E.
Bergström, Göran
Ekwall, Anna-Karin Hultgard
Rudin, Anna
Kastbom, Alf
Sjöwall, Christopher
Jacobsson, Lennart T. H.
Kihlberg, Jan
Gjertsson, Inger
Holmdahl, Rikard
Publication Year :
2023

Abstract

Objective. This study was undertaken to develop and characterize a multiplex immunoassay for detection of autoantibodies against peptides derived from proteins known to play a role in development of arthritis and that are also expressed in joints.Methods. We selected peptides from the human counterpart of proteins expressed in the joints, based on mouse models that showed these to be targeted by pathogenic or regulatory antibodies in vivo. Using bead-based flow immunoassays measuring IgG antibodies, we selected triple helical or cyclic peptides, containing the epitopes, to avoid collinear reactivity. We characterized the analytical performance of the immunoassay and then validated it in 3 independent rheumatoid arthritis (RA) cohorts (n = 2,110), Swedish age- and sex-matched healthy controls, and patients with osteoarthritis (OA), patients with psoriatic arthritis (PsA), and patients with systemic lupus erythematosus (SLE).Results. Screening assays showed 5 peptide antigens that discriminated RA patients from healthy controls with 99% specificity (95% confidence interval [CI] 98-100%). In our validation studies, we reproduced the discriminatory capacity of the autoantibodies in 2 other RA cohorts, showing that the autoantibodies had high discriminatory capacity for RA versus OA, PsA, and SLE. The novel biomarkers identified 22.5% (95% CI 19-26%) of early RA patients seronegative for anti-cyclic citrullinated peptide and rheumatoid factor. The usefulness of the biomarkers in identifying seronegative RA patients was confirmed in validation studies using 2 independent cohorts of RA patients and cohorts of patients with OA, PsA, and SLE.Conclusion. A multiplex immunoassay with peptides from disease-related proteins in joints was found to be useful for detection of specific autoantibodies in RA serum. Of note, this immunoassay had high discriminatory capacity for early seronegative RA.<br />Funding Agencies|Swedish Foundation for Strategic Research, Vinnova, Swedens innovation agency; Swedish Research Council; Knut and Alice Wallenberg Foundation; Swedish Rheumatism Association; Foundation for Assistance to Disabled People in Skane, ALF VastraGotaland Region, Sweden; Swedish Heart Lung Foundation

Details

Database :
OAIster
Notes :
application/pdf, English
Publication Type :
Electronic Resource
Accession number :
edsoai.on1428027581
Document Type :
Electronic Resource
Full Text :
https://doi.org/10.1002.art.42463