Autoantibodies against citrullinated and native proteins and prediction of rheumatoid arthritis-associated interstitial lung disease: a nested case–control study
Authors' conclusion
Specific ACPA and anti-native protein antibodies improve RA-ILD prediction.
Study context
- Population
- Patients with RA in the Brigham RA Sequential Study
- Participants
- 84 vs 233
- Comparison
- Incident RA-ILD cases vs RA-noILD controls: fine specificity anti-citrullinated protein antibodies (ACPA) and anti-native protein antibodies from stored serum prior to RA-ILD onset
- RA-ILDn = 84
- RA-noILDn = 233reference
- Outcome
- Incident RA-ILD associated with fine specificity ACPA and anti-native protein antibodies (OR, 95% CI)
Methodological detailswithin the Brigham RA Sequential Study, matched on time of blood collection, age, sex, RA duration and RF status, logistic regression, internal validation
- Within the Brigham RA Sequential Study
- Matched on time of blood collection, age, sex, RA duration and RF status
- Logistic regression
- Internal validation
Main finding
As reported in the abstract
Fine specificity antibodies associated with RA-ILD (aOR)
- IgA2 to citrullinated histone 4, OR per log-transformed unit
- 0.08 (95% CI 0.03-0.22)
- IgA2 to citrullinated histone 2A, OR
- 4.03 (95% CI 2.03-8.00)
- IgG to cyclic citrullinated filaggrin, OR
- 3.47 (95% CI 1.71-7.01)
- IgA2 to native cyclic histone 2A, OR
- 5.52 (95% CI 2.38-12.78)
- IgA2 to native histone 2A, OR
- 4.60 (95% CI 2.18-9.74)
- IgG to native cyclic filaggrin, OR
- 2.53 (95% CI 1.47-4.34)
Observational data: associations, not effects.
Further findings
Prediction of RA-ILD: six antibodies vs all clinical factors combined (optimism-corrected AUC)
- Six antibodies, optimism-corrected AUC
- 0.84
- All clinical factors combined, optimism-corrected AUC
- 0.73
- Internal validation
Risk score at 50% predicted RA-ILD probability
- Score without biomarkers
- 2.6
- Score with biomarkers
- 5.9
- Specificity for RA-ILD, both scores
- ≥93%
- Clinical factors: smoking, disease activity, GC use, obesity
Original publication
Autoantibodies against citrullinated and native proteins and prediction of rheumatoid arthritis-associated interstitial lung disease: a nested case–control study. Lancet Rheumatol. Published 24 January 2023. doi:10.
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