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Antibodies against carbamylated proteins are present in primary Sjögren's syndrome and are associated with disease severity
  1. Brith Bergum1,
  2. Catalin Koro1,
  3. Nicolas Delaleu1,
  4. Magne Solheim2,
  5. Annelie Hellvard1,3,
  6. Veronika Binder1,
  7. Roland Jonsson1,
  8. Valeria Valim4,
  9. Daniel S Hammenfors5,
  10. Malin V Jonsson1,6,
  11. Piotr Mydel1,3
  1. 1Broegelmann Research Laboratory, Department of Clinical Science, University of Bergen, Bergen, Norway
  2. 2Department of Clinical Science, University of Bergen, Bergen, Norway
  3. 3Małopolska Centre of Biotechnology, Jagiellonian University, Krakow, Poland
  4. 4Department of Clinical Medicine, Centre of Health Science, Federal University of Espírito Santo, Vitoria, Brazil
  5. 5Department of Rheumatology, Haukeland University Hospital, University of Bergen, Bergen, Norway
  6. 6Department of Clinical Dentistry, Section for Oral and Maxillofacial Radiology, University of Bergen, Bergen, Norway
  1. Correspondence to Dr Piotr Mydel, Broegelmann Research Laboratory, Department of Clinical Science, University of Bergen, The Laboratory Building, 5th floor, Bergen N-5021, Norway; piotr.mydel{at}k2.uib.no

Abstract

Objectives Herein, we investigate the presence and prognostic value of autoantibodies against carbamylated proteins (anti-CarP) in the serum of patients with primary Sjögren's syndrome (pSS).

Patients and methods Serum levels of anti-CarP antibodies were measured in Norwegian patients with pSS (n=78) and corresponding controls (n=74) using ELISA and analysed in relation with exocrine gland function, degree of salivary gland inflammation, signs of ectopic germinal centre (GC) formation and immunological markers. For univariate comparisons, the Mann–Whitney U test and χ2 or Fisher's exact tests were used. Correlations were assessed with Spearman's rank testing. Multivariate regression analyses were used to assess the effect of anti-CarP positivity on clinical manifestations.

Results Of the patients with pSS, 27% were positive for anti-CarP IgG antibodies. Levels of anti-CarP correlated positively with total IgG, IgM, rheumatoid factor and β2-microglobulin. Importantly, after adjusting for confounding factors, patients positive for anti-CarP had significantly higher focus score. Furthermore, positive anti-CarP status coincided with 9.2-fold higher odds of having developed GC-like structures in the minor salivary glands. As a patient group considered having worse disease outcome, individuals with ectopic GC-like structures also presented with significantly higher levels of anti-CarP antibodies.

Conclusions Presence of anti-CarP in patients with pSS is strongly associated with increased focal lymphocytic infiltration, formation of ectopic GC-like structures in minor salivary glands, and diminished salivary gland function. Even taking into consideration our relatively small cohort we believe that anti-CarP antibodies offer new possibilities for identifying patients with more active disease and at risk of developing additional comorbidity.

  • Sjøgren's Syndrome
  • Autoantibodies
  • Inflammation

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