Background/Purpose: Interstitial lung disease (ILD) is associated with significant morbidity and mortality in rheumatoid arthritis (RA). There are currently no proven biomarkers for ILD in RA. Cytokines, because of their important role in RA pathogenesis, as promising candidates to serve as biomarkers for ILD . In the current analysis, we examined the association between multiple cytokines and ILD in an RA cohort.

Methods: We studied members of an RA cohort recruited during a visit to a rheumatologist.  All patients had comprehensive assessments at baseline and annual follow-up, including collection of a serum sample which was stored. Medical records, including imaging reports, were reviewed thoroughly to assess comorbidity. We considered ILD to be present if an X-ray or computed tomography of the chest, or a lung biopsy were diagnostic of ILD. We measured the concentration of 38 cytokines in stored serum, using ELISA. We used stepwise logistic regression to identify cytokines associated with ILD, adjusting for age and sex as covariates. We show odds ratios (95% CI) to show strength of association.

Results: We studied 1328 patients, of whom 1204 had a stored serum sample for cytokine measurement. Of these, 86 had ILD (6.5%).  Using stepwise logistic regression, the concentration of six cytokines was independently associated with ILD.  The following three were associated with increased odds of ILD: growth-related oncogene (GRO), 2.14 (1.33, 3.44); tumor necrosis factor-alpha (TNF-a), 1.56 (1.12, 2.17); and interleukin-2 (IL-2), 1.73 (1.4, 2.15). The following three were associated with decreased odds of ILD:  macrophage inflammatory protein-1-alpha (MIP1-a), 0.79 (0.62, 1.00); macrophage-derived chemokine (MDC) 0.48 (0.32, 0.72); and granulocyte colony stimulating factor (GCSF), 0.51 (0.34, 0.78). (Table 1). The area under the ROC curve for a model containing these cytokines plus age and sex was 0.776, while that for a model containing only age and sex was 0.63.

Table 1. Cytokines in RA-ILD patients.

Conclusion: The profile of serum cytokine concentrations is significantly associated with the presence of ILD, with some cytokines being associated with increased risk, others with decreased risk. These findings may indicate the potential pathogenic of these cytokines in ILD among RA patients. In addition, these cytokines offer promise as potential biomarkers that could be used for the early identification of patients at risk for developing ILD.

Disclosure: Nothing to disclose