Lung Fibrosis in Scleroderma Linked to Immune System and Cell Matrix in Study

Factors in the innate immune system, as well as those in the extracellular matrix surrounding cells, are likely involved in the development of lung fibrosis in scleroderma patients, researchers suggest after linking gene mutations to the condition.

Since risk factors for scleroderma typically belong to other parts of the immune system, these insights may help scientists to better understand the mechanisms that lead to scleroderma on one hand, and lung fibrosis on the other.

Researchers at Medical College of Xiamen University in China realized the reason why only some scleroderma patients develop lung fibrosis may lie in genetic differences among patients.

Since plenty of studies have examined gene variation in scleroderma, their study, “The status of pulmonary fibrosis in systemic sclerosis is associated with IRF5, STAT4, IRAK1, and CTGF polymorphisms,” made use of previously published research to draw conclusions. The work appeared in the journal Rheumatology International.

The team gathered data to perform what is known as a meta-analysis. In this approach, researchers pool data from published studies and then do an analysis; results are considered to provide stronger evidence of the link under investigation.

The researchers included 17 studies, which investigated a total of eight gene variants. Two of the variants — all were single base-pair changes — were found in the same gene.

The analysis revealed that gene variation in four genes — IRF5, STAT4, CTGF, and IRAK1 — was linked to lung fibrosis in scleroderma. No association was established in a second mutation in the IRF5 gene.

The remaining investigated genes have been linked to scleroderma risk in earlier studies.

Risk genes for scleroderma often code for molecules of the adaptive immune system — mirroring autoimmune disease processes. But the team identified lung fibrosis genes that were crucial for other functions. IRF5, STAT4, and IRAK1 are known players of the innate immune response — a first-line defense against intruding microbes.

But CTGF belongs to a family of proteins involved in the abnormal synthesis of extracellular matrix proteins that is seen in fibrotic diseases. The extracellular matrix is a meshwork of molecules that surrounds cells.

“This result suggests a role of innate immunity and ECM [extracellular matrix] synthesis in the manifestation of pulmonary fibrosis in SSc [systemic sclerosis],” the team wrote.

Based on the results, the researchers argue that scleroderma and lung fibrosis development may be guarded by distinct mechanisms.