Graduation Date

Fall 12-19-2025

Document Type

Thesis

Degree Name

Master of Science (MS)

Programs

Medical Sciences Interdepartmental Area

First Advisor

Bryant R. England

Second Advisor

Ted R. Mikuls

Third Advisor

Geoffrey M. Thiele

Abstract

Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is a common extra-articular complication of rheumatoid arthritis (RA). Measuring peripheral blood biomarkers represents an appealing strategy to inform the screening and prediction of RA-ILD. In these studies, I aimed to further characterize the associations of peripheral blood biomarkers with prevalent and incident RA-ILD. First, I evaluated the associations of matrix metalloproteinases (MMPs) with RA-ILD among a multicenter cohort of RA U.S. Veteran patients (n = 2,312). Higher concentrations of MMP-7 and MMP-9 were independently associated with both prevalent and incident RA-ILD, including a nearly four-fold increased odds of prevalent RA-ILD (adjusted odds ratio 3.78 [95% CI: 1.86-7.65]) and greater than two-fold increased risk of incident RA-ILD (adjusted hazard ratio 2.45 [95% CI 1.55-3.88]) among those in the highest quartile of MMP-7 concentrations. I next evaluated the performance of a multibiomarker score consisting of seven idiopathic pulmonary fibrosis (IPF)-associated peripheral biomarkers in independent derivation and validation cohorts. This IPF-derived biomarker score was similarly associated with both prevalent RA-ILD (adjusted odds ratio 2.14 [95% CI 1.18-3.87]) and incident RA-ILD (adjusted hazard ratio 2.45 [95% CI 1.55-3.88]). These findings lend further support to a shared etiopathogenesis of RA-ILD and IPF, while also providing support for a potential pathogenic role of MMPs in RA-ILD. Future studies of peripheral biomarkers in RA-ILD are needed to clarify not only their roles in diagnosis and prediction, but also their associations with disease severity, progression, and treatment response.

Comments

2025 Copyright, the authors

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