Immune Cell Clues Uncover Systemic Sclerosis Severity

Researchers have found a cellular signature that might explain why patients with systemic sclerosis experience differing disease severity. This discovery could lead to better treatments by targeting the specific immune cell abnormalities driving the disease.

Cellular Signature Identified

A team of researchers from Japan has discovered a connection between the behavior of particular immune cells and the severity of systemic sclerosis. Their research, published in Nature Communications, suggests that variations in how the disease manifests might be linked to the proliferation of certain immune cells in key organs.

Systemic sclerosis, a rare autoimmune disorder, often hardens the skin and causes Raynaud’s phenomenon. The illness may affect internal organs like the lungs and kidneys, sometimes causing severe complications.

“We know that immune dysregulation causes vascular damage and tissue fibrosis in systemic sclerosis. However, it remains unclear why skin symptoms and the level of organ involvement differ from patient to patient.”

—Hiroshi Shimagami, Lead Author

Exploring Immune Cell Behavior

The scientists analyzed blood and tissue samples from patients with systemic sclerosis to investigate the condition. They looked at gene expression differences on a cell-by-cell basis. Additionally, they examined cell surface proteins to identify disease biomarkers.

Masayuki Nishide, senior author, said the findings were intriguing. They pinpointed a specific subset of immune cells, the EGR1-expressing subpopulation of CD14+ monocytes, strongly linked to scleroderma renal crisis, a serious kidney complication.

According to the National Institutes of Health, approximately 75,000 to 100,000 people in the United States have systemic sclerosis (NIH, 2024).

Understanding the Mechanisms

Immune cells are intended to fight infection and illness, but they can become inappropriately activated through gene expression. In this instance, CD14+ monocytes transformed into destructive macrophages. These promote inflammation near the kidneys, contributing to organ thickening and scarring.

Researchers also found that CD8+ T cells with a type II interferon signature, making them particularly inflammatory, were linked to interstitial lung disease. The EGR1-expressing CD14+ monocytes and these peculiar CD8+ T cells accumulate in the kidney or lung, respectively, and produce factors that worsen the disease.

“Taken together, our single-cell analysis of patient samples show that specific abnormalities in distinct subsets of immune cell are associated with different clinical symptoms of systemic sclerosis, particularly organ manifestations,”

—Dr. Shimagami

Given the limited treatment options available for those with systemic sclerosis, this research suggests promising possibilities for developing new therapeutic strategies. Predicting the disease using biomarkers and preventing severe organ involvement could positively impact patients’ lives.