CHICAGO – Rheumatoid arthritis–associated interstitial lung disease and idiopathic pulmonary fibrosis without RA share a common genetic underpinning whose hallmark is a gain-of-function MUC5B gene promoter variant that cranks up mucin production in the lungs, Pierre-Antoine Juge, MD, reported at the annual meeting of the American College of Rheumatology.
He presented a seven-country genetic case-controlof 620 patients with RA-associated interstitial lung disease (RA-ILD), 614 with RA but no ILD, and 5,448 unaffected controls. The key finding was that the MUC5B promoter variant rs35705950, already known to be the strongest genetic risk factor for idiopathic pulmonary fibrosis (IPF), also contributes substantially to the risk of RA-ILD.
Indeed, the presence of the MUC5B promoter variant in patients with RA proved to be associated with substantially higher risk of RA-ILD than the previously recognized risk factors for RA-ILD, including cigarette smoking and the human leukocyte antigen locus for RA, according to Dr. Juge, a rheumatologist at Bichat Hospital–Claude Bernard and Paris Diderot University.
MUC5B encodes for mucin production in the lungs. The increased risk of RA-ILD conferred by the presence of the MUC5B promoter variant was confined to the 41% of RA-ILD patients with a pattern of usual interstitial pneumonia (UIP) or possible UIP on high-resolution CT. The presence of the MUC5B promoter variant in RA patients was independently associated with an adjusted 6.1-fold increased risk of ILD with a UIP pattern on imaging – marked by honeycombing, reticular abnormalities, and subpleural involvement – compared with RA patients who didn’t possess the gain-of-function MUC5B variant. The risk of other types of RA-ILD wasn’t affected by the presence or absence of the MUC5B variant.
The MUC5B promoter variant was not a risk factor for development of RA.
These findings have potentially important implications for clinical practice, given that clinically significant ILD is present in about 10% of all RA patients and occult ILD is detectable using high-resolution CT in up to half of individuals with RA, Dr. Juge observed. Detection of the MUC5B promoter variant could be used to screen patients with RA for preclinical ILD. Also, there is now a sound rationale to study drugs known to be effective for IPF as potential treatments for RA-ILD, he said.
Dr. Juge reported having no financial conflicts regarding the study, which was sponsored by the National Institutes of Health, the U.S. Department of Defense, the French Rheumatology Society, the Japanese Society for the Promotion of Science, Fondation Arthritis, and the Nina Ireland Program for Lung Health.
In conjunction with his presentation in Chicago, the study was published online in the New England Journal of Medicine ().
SOURCE: Juge P-A et al. .