The lung may play a role in the pathogenesis of rheumatoid arthritis

Abstract

Multiple studies have identified strong associations between the lung and rheumatoid arthritis (RA). Such studies identify a high prevalence of lung disease, both airways and parenchymal disease, in subjects with clinically classifiable RA. It has been suggested that lung disease in RA results from targeting of the lung from circulating autoimmunity or other factors such as medications. However, findings that lung disease, specifically inflammatory airways disease, and lung generation of autoimmunity can be present before the onset of joint symptoms suggest that immune reactions in the lung may be involved in the initial development of RA-related autoimmunity. Herein we review these issues in detail, as well as outline a potential research agenda to understand the natural history of lung involvement in RA and its relation to the overall pathogenesis of RA.

The Roles of Cigarette Smoking and the Lung in the Transitions Between Phases of Preclinical Rheumatoid Arthritis

“…While rates vary depending on RA duration, smoking exposure, medication history, and sensitivity of the testing modality, 8–36% of RA patients have pulmonary function tests suggesting airways obstruction, 60–80% of RA patients have airways disease on high-resolution computed tomography (CT) scans, and parenchymal disease is present in up to 79% of RA patients [10]. …”

“…The anatomic sites that may be important in the development of RA include the lung, respiratory tract, periodontum, gut, bladder, and reproductive tract [9]. However, the lung and respiratory tract have the most evidence in support of being an initiating site for RA [10]. …”

The role for neutrophil extracellular traps in cystic fibrosis autoimmunity

“…Studies of chronic inflammatory diseases, such as rheumatoid arthritis (RA), lupus, or granulomatosis with polyangiitis, have demonstrated a strong link between neutrophil-mediated inflammation and autoimmunity (18)(19)(20). Moreover, in RA, this inflammation is thought to initiate in the lung as a result of environmental factors, e.g., microbes or smoking (21). In particular, NETosis, a mechanism by which neutrophils extrude their DNA and protein contents to form neutrophil extracellular traps (NETs), is thought to lead to the breaking of tolerance to citrullinated and carbamylated proteins in RA patients (22).…”

Estimating driver-tissues by robust selective expression of genes associated with complex diseases or traits

“…Unexpectedly, the lung is prioritized as the most significant tissue. However, there have been multiple studies suggesting the lung may play a role in the pathogenesis of RA [43]. There are also studies suggesting lung disease as a major contributor to morbidity and mortality for RA [44].…”