Genomic and Serological Rheumatoid Arthritis Biomarkers, MUC5B Promoter Variant, and Interstitial Lung Abnormalities

Area of Science:

• Pulmonary Medicine
• Rheumatology
• Genetics

Background:

• Rheumatoid arthritis (RA) is frequently observed with interstitial lung disease (ILD).
• Previous studies focused on RA patients, leaving a gap in understanding RA risk in broader populations.
• The interplay between RA genetic risk, pulmonary fibrosis risk, and early lung injury markers requires further investigation.

Purpose of the Study:

• To investigate the association of RA genetic and serological biomarkers with interstitial lung abnormalities (ILA).
• To determine if the MUC5B risk allele (rs35705950 T) modifies the relationship between RA biomarkers and ILA.
• To assess these associations in large, diverse cohorts using computed tomography (CT) scans.

Main Methods:

• Utilized data from the Multi-Ethnic Study of Atherosclerosis (MESA) and COPDGene cohorts.
• Modeled associations of RA-risk HLA-DRB1 alleles and serum RA autoantibodies with ILA using logistic regression.
• Adjusted for demographic factors, smoking history, BMI, and genetic ancestry principal components.

Main Results:

• RA-risk HLA-DRB1 alleles showed no significant association with ILA in either cohort.
• Higher serum IgA rheumatoid factor (RF) and anti-cyclic citrullinated peptide were associated with increased odds of ILA in MESA.
• In smokers without baseline ILA, increased IgM RF levels predicted subsequent ILA development over 10 years.

Conclusions:

• RA-related HLA-DRB1 alleles are not independently associated with interstitial lung abnormalities (ILA).
• Elevated serum rheumatoid factor (RF) levels, particularly IgM RF in smokers, are associated with an increased risk of developing ILA.
• The MUC5B risk allele did not significantly alter these observed associations.