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Specific ACPAs and Autoantibodies Lead to RA-Associated ILD

Feb 20, 2023 6:26 pm

A BRASS registry study shows that specific isotypes of anti-citrullinated protein antibodies (ACPAs) can be associated with incident rheumatoid arthritis-associated ILD (RA-ILD). Early idtentification of RA-ILD is extremely important as it is a major contributor to premature death among patients with RA.

This nested case–control study utilized data generated prospectively in the Brigham Rheumatoid Arthritis Sequential Study (BRASS) registry, matching RA-ILD patients with RA without ILD. ACPA and anti-native protein antibodies were assayed and associations were calculated from logistic regression models.

When comparing 84 incident RA-ILD cases (mean age 67) with 233 RA controls (without ILD; mean age 66 years), they identified six fine-specificity antibodies that were significanly associated with RA-ILD, including:

  • IgA2 to citrullinated histone 4 (adjusted OR 0·08)
  • IgA2 to citrullinated histone 2A (aOR 4·03)
  • IgG to cyclic citrullinated filaggrin (aOR 3·47)
  • IgA2 to native cyclic histone 2A (aOA 5·52)
  • IgA2 to native histone 2A (aOR 4·60)
  • IgG to native cyclic filaggrin (aOR 2·53)

These autoantibodies better predicted RA-ILD better than did all clinical factors (AUC 0·84 versus 0·73).  Moreover these antibodies could be used with clinical factors (smoking, disease activity, glucocorticoid use, and obesity) to develop a predictive risk score with a specificity of 93% or higher for RA-ILD.

More studies are needed to show if these antibodies have clinical utility in predicting the development of ILD in patients with rheumatoid arthritis.


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The author has no conflicts of interest to disclose related to this subject