Identification of circulating autoantibodies to non-modified proteins associated with ACPA status in early rheumatoid arthritis

Lucía Lourido; Vijay Joshua; Monika Hansson; Ronald Sjöberg; Elisa Pin; Cristina Ruiz-Romero; Peter Nilsson; Lars Alfredsson; Lars Klareskog; Francisco J Blanco

doi:10.1093/rheumatology/keae007

Identification of circulating autoantibodies to non-modified proteins associated with ACPA status in early rheumatoid arthritis

Rheumatology (Oxford). 2024 Jan 9:keae007. doi: 10.1093/rheumatology/keae007. Online ahead of print.

Authors

Affiliations

¹ Unidad de Proteómica. Grupo de Investigación de Reumatología (GIR). Instituto de Investigación Biomédica de A Coruña (INIBIC), Complexo Hospitalario Universitario de A Coruña (CHUAC), Sergas. Universidade da Coruña (UDC), C/As Xubias de Arriba 84, A Coruña, 15006, España.
² Division for Rheumatology, Department of Medicine, (Solna) Karolinska Institutet, Stockholm, Sweden.
³ Department of Protein Science, SciLifeLab, KTH Royal Institute of Technology, Stockholm, Sweden.
⁴ Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Av. Monforte de Lemos, 3-5. Pabellón 11, Madrid, 28029, España.
⁵ Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
⁶ Grupo de Investigación en Reumatología y Salud (GIR-S), Centro Interdisciplinar de Química e Bioloxía (CICA), Departamento de Fisioterapia, Medicina y Ciencias Biomédica, Facultad de Fisioterapia, Universidade da Coruña (UDC), A Coruña, 15006, Spain.

PMID: 38195995
DOI: 10.1093/rheumatology/keae007

Abstract

Objectives: To discover autoantibodies to non-modified proteins associated with the presence/absence of anticitrullinated protein antibodies (ACPA) in rheumatoid arthritis (RA).

Methods: The autoantibody repertoire of 80 ACPA negative and 80 ACPA positive RA subjects from the Swedish population-based Epidemiological Investigation of RA (EIRA) cohort was screened using a suspension bead array built on protein fragments earlier described as autoimmunity targets. Four autoantibodies positive in the initial screening were validated in another set of EIRA samples containing 317 ACPA-positive, 302 ACPA-negative and 372 age- and sex-matched controls. The relationship between the four autoantibodies and lung abnormalities on high-resolution computed tomography (HRTC) was examined in 93 early RA patients from LURA cohort. Association between the autoantibodies, smoking and MHC class II alleles was assessed by logistic regression analysis.

Results: : Anti-ANOS1 and anti-MURC IgG levels were associated with ACPA-positive status (OR = 3.02; 95% CI 1.87-4.89; and OR = 1.86; 95% CI 1.16-2.97, respectively) and increased in ACPA-positive patients compared with controls. Anti-ANOS1 IgG was associated with smoking habit (OR = 2.11; 95% CI 1.22-3.69) and anti-MURC IgG with the presence of the MHC class II "shared-epitope" genes (OR = 1.95; 95% CI 1.11-3.46). Anti-TSPYL4 IgG was associated with ACPA-negative (OR = 0.41; 95% CI 0.19-0.89). Anti-TSPYL4 IgG and anti-MAP2K6 IgG levels were increased in the ACPA-negative patients compared with controls. Presence of anti-MAP2K6 IgG and anti-TSPYL4 IgG correlated negatively with HRCT-defined lung abnormalities.

Conclusions: These four autoantibodies may be useful in diagnostics and in predicting clinical phenotypes of RA.

Keywords: Rheumatoid arthritis; anti-citrullinated protein autoantibodies (ACPAs); biomarkers; novel circulating autoantibodies; proteomics.