(Press-News.org) Osaka, Japan – Treating rare diseases can be complicated at the best of times, and it gets even more complicated when different patients with the same disease exhibit different symptoms. Now, researchers from Japan have reported a cellular signature that might explain why some patients with autoimmune disease are stable while others face life-threatening complications.
In a study to be published in Nature Communications, a multi-institutional research team led by The University of Osaka has revealed that, for patients with systemic sclerosis, this variation in disease severity seems to be due to the proliferation of certain immune cells in key organs.
Systemic sclerosis is a rare autoimmune disease that is mainly characterized by hardening of the skin, as well as Raynaud’s phenomenon, in which the fingers and toes change color and lose sensation in cold temperatures. In addition to these symptoms, systemic sclerosis can affect internal organs, such as the lungs and kidneys, with serious consequences.
“We know that immune dysregulation causes vascular damage and tissue fibrosis in systemic sclerosis,” says lead author, Hiroshi Shimagami. “However, it remains unclear why skin symptoms and the level of organ involvement differ from patient to patient.”
To explore this, the researchers took blood and tissue samples from patients with systemic sclerosis and analyzed them cell by cell, looking for differences in gene expression. Additionally, proteins on the cell surface were examined to identify biomarkers of disease, which are useful for identifying and treating diseases in earlier stages.
“The results were intriguing,” explains Masayuki Nishide, senior author. “We identified a specific subset of immune cells, the EGR1-expressing subpopulation of CD14+ monocytes, that were clearly associated with scleroderma renal crisis, a serious kidney complication in patients with systemic sclerosis.”
While immune cells usually help the body fight infection and disease, in certain cases they can be inappropriately activated through gene expression. In this instance, CD14+ monocytes differentiated – or transformed – into destructive macrophages, which can further promote inflammation near the kidneys and contribute to the thickening and scarring of internal organs.
In addition, the researchers found that CD8+ T cells with a type II interferon signature, which makes the immune cells particularly aggressive and inflammatory, were linked to progressive interstitial lung disease. EGR1-expressing CD14+ monocytes and these peculiar CD8+ T cells are likely to accumulate in the kidney or the lung, respectively, and produce or recruit other factors that contribute to disease progression.
“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,” says Dr Shimagami.
Given that few treatment options are currently available for patients with systemic sclerosis, this study suggests promising avenues for the development of new therapeutic strategies. Predicting disease through biomarkers and preventing severe organ involvement would have a significant, positive impact on these patients’ quality of life.
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The article, “Single-cell analysis reveals immune cell abnormalities underlying the clinical heterogeneity of patients with systemic sclerosis,” is to be published in Nature Communications at DOI: https://doi.org/10.1038/s41467-025-60034-7
About The University of Osaka
The University of Osaka was founded in 1931 as one of the seven imperial universities of Japan and is now one of Japan's leading comprehensive universities with a broad disciplinary spectrum. This strength is coupled with a singular drive for innovation that extends throughout the scientific process, from fundamental research to the creation of applied technology with positive economic impacts. Its commitment to innovation has been recognized in Japan and around the world, being named Japan's most innovative university in 2015 (Reuters 2015 Top 100) and one of the most innovative institutions in the world in 2017 (Innovative Universities and the Nature Index Innovation 2017). Now, Osaka University is leveraging its role as a Designated National University Corporation selected by the Ministry of Education, Culture, Sports, Science and Technology to contribute to innovation for human welfare, sustainable development of society, and social transformation.
Website: https://resou.osaka-u.ac.jp/en
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