Genetics and pathogenesis of connective tissue disease-associated interstitial lung disease

Connective tissue diseases (CTD) are a broad category of diseases with autoimmune etiology and multi-system involvement. The lung seems to be involved in some form in most CTDs. Interstitial lung disease (ILD) is the prototypic lung manifestation and is seen in 2%-50% of patients with CTDs.[1] It leads to significant morbidity and mortality. Unfortunately, the ubiquitous involvement across CTDs, along with the possible benefit of treating this manifestation, has not translated into a good understanding of its pathogenesis or treatment. We must aim for a better understanding of the genetic determinants of this manifestation (to help identify those who are at risk) as well as its pathogenesis (to help identify therapeutic targets). This review aims to provide a summary of the key genetic determinants of CTD-ILD as well as the key players of the pathogenic pathway of this manifestation.