Background/Purpose:  Interstitial lung disease (ILD) is an extra-articular manifestation of rheumatoid arthritis (RA) which contributes to increased morbidity and mortality. Clinico-epidemiological data indicate some overlap in disease course between RA-ILD and idiopathic pulmonary fibrosis (IPF), particularly in subsets of RA-ILD patients with UIP-like pathology. We therefore evaluated levels of specific peripheral blood protein markers in patients with RA-ILD and IPF to determine molecular profiles indicative of shared disease pathogenesis.

Methods:  A cohort of patients that met ACR classification criteria for rheumatoid arthritis were enrolled and subclassified as having RA-no ILD versus RA-ILD (mild vs. advanced parenchymal lung abnormalities) based on high resolution computed tomography scans of the chest (HRCT). A cohort of patients with IPF was also enrolled through Brigham and Women’s Hospital. Standard solid phase enzyme-linked immunosorbent assays (ELISAs) were used to assess serum levels of matrix metalloproteinase 7 (MMP-7) and interferon-ϒ-inducible protein 10 (IP-10), which had previously been found to be significantly elevated in RA-ILD. Levels of serum biomarkers were compared using Mann U Whitney testing.

Results:  71 patients with RA were enrolled and classified as RA-no ILD (n=22) versus RA-ILD (n=49). Serum specimens were obtained from these patients as well as a comparator cohort of IPF patients (n=44). 72.7% (n=16) of patients in the RA-no ILD group, 63.3% (n=31) of patients in the RA-ILD and 40.9% (n=18) of patients in the IPF group were women. The average age of the patients in the RA-ILD and IPF groups were 65 and 66 years, respectively, vs 50 years in the RA-no ILD group (p=<0.0001). 63.6% (n=28) of the IPF patients, 55% (n=27 ) of the RA-ILD patients and 36.4% (n=8) of the RA-no ILD patients were smokers. ELISA-based measurement of serum MMP-7 revealed significantly increased levels in patients with RA-ILD and IPF (8.19 ng/ml vs 6.16 ng/ml, p=0.02). IP-10 levels were also significantly elevated in both RA-ILD and IPF patients (209.71 pg/ml vs 187.61 pg/ml, p=0.71). In contrast, patients with RA-no ILD had significantly lower levels of MMP-7 (2.98 ng/ml) and IP-10 (82.32 pg/ml) compared to patients with RA-ILD (MMP-7: p=<0.0001, IP-10: p=0.001) and patients with IPF (MMP7: p=<0.0001, IP-10: p=0.003).

Conclusion:  Serum levels of both MMP-7 and IP-10 were elevated in patients with IPF and RA-ILD relative to RA patients without evidence of ILD. This overlap in biomarker signatures encompassing both inflammatory (IP-10) and remodeling (MMP-7) pathways supports a possible link in pathogenesis that may suggest common therapeutic targets in RA-ILD and IPF.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/common-biomarker-elevations-in-idiopathic-pulmonary-fibrosis-and-rheumatoid-arthritis-associated-interstitial-lung-disease/