The following is a summary of “Autoantibodies against citrullinated and native proteins and prediction of rheumatoid arthritis-associated interstitial lung disease: a nested case–control study,” published in the February 2023 issue of  Rheumatology by  Kronzer, et al.

Interstitial lung disease (ILD) is a common complication of rheumatoid arthritis and a major cause of death in this patient population. An improved ability to anticipate rheumatoid arthritis-related ILD is critical for facilitating earlier diagnosis and therapy. Here, They set out to determine whether or not the presence of anti-citrullinated protein antibodies (ACPAs) was a risk factor for developing ILD in people with rheumatoid arthritis. Cases of incident rheumatoid arthritis-associated ILD diagnosed between March 1, 2003, and April 14, 2016, and control patients with rheumatoid arthritis who did not have ILD were matched on the following characteristics: time of blood collection, age, sex, duration of rheumatoid arthritis, and rheumatoid factor status. Before the start of ILD in rheumatoid arthritis.

They used a multiplex test to assess ACPA and anti-native protein antibodies in pre-clinical serum samples. Adjusting for prospectively collected covariates, They used logistic regression models to determine odds ratios (ORs) and 95% CIs for ILD related to rheumatoid arthritis. Through a process of internal validation, They calculated optimism-adjusted AUCs. Finally, they calculated a risk score for ILD due to RA using model coefficients. They found 84 incident cases of ILD in patients with rheumatoid arthritis (mean age 67 [SD 10] years; 65 [77%] female and 19 [23%] male; 76 [90%] White); and 233 controls without ILD in patients with rheumatoid arthritis (mean age 66 [11] years; 186 [80%] female and 47 [20%] male; 219 [94%] White). They found that rheumatoid arthritis is linked to ILD in 6 individuals with antibodies with a fine specificity. 

IgA2 to citrullinated histone 4 (adjusted OR 0.08 [95% CI 0.03 to 0.22] per log-transformed unit), IgA2 to citrullinated histone 2A (4.03 [2.03 to 8.00]), IgG to cyclic citrullinated filaggrin (3.47 [1.71 to 7.01]), IgA2 to native cyclic histone 2A (5.52 [2.38 to 12.78]), I The probability of ILD due to RA was predicted by these 6 antibodies better than by any combination of clinical variables (optimism-corrected AUC 0.84 versus 0.73). Using these antibodies in conjunction with clinical factors (smoking, disease activity, glucocorticoid use, and obesity), they developed a risk score for rheumatoid arthritis-associated ILD with a specificity of 93% or higher at the 50% predicted probability of developing rheumatoid arthritis-associated ILD. Certain ACPAs and anti-native protein antibodies enhance thes the prediction of rheumatoid arthritis-related ILD. These results imply that synovial protein antibodies play a role in the aetiology of rheumatoid arthritis-associated ILD and, once validate. Onceal studies that these antibodies may have clinical usefulness in predicting the development of ILD in patients with rheumatoid arthritis.