A collaborative research study has found the genetic basis for the link between macrophages, a key immune cell, and systemic sclerosis (SSc), a rare chronic autoimmune disease. Symptoms include changes in the texture and appearance of the skin due to increases collagen in connective tissue. The disease can impact other organs and systems including blood vessels, muscles, heart, digestive system, lungs, and kidneys. SSc symptoms can manifest in the presence of other autoimmune disorders, a condition known as mixed connective disorder. The results of the study were published in Annals of Rheumatic Diseases.
The study focuses on the role of monocyte-derived macrophages (MDMs) in susceptibility to SSc. The team performed RNA sequencing, genotyping, and expression analysis of MDMs from 57 SSc patients and 15 control samples. Multiple macrophage genes were found to play a role in the development of SSc. The team found that the gene, GSDMA, is upregulated in macrophages from the SSc patients but not in the skin. GSDMA is a member of the recently discovered gasdermin protein family that are involved in cellular swelling and lysis. This results of this study point to macrophages being responsible for the impact of GSDMA on the disease.
"Investigating how genetic variation is responsible for systemic sclerosis is a colossal task. By looking at immune cells such as macrophages, we can generate specific hypotheses that will allow us to understand how these cells cause damage," added Dr Jacques Behmoaras, co- lead principal investigator from Centre for Complement and Inflammation Research, Imperial College London.