A research group led by Graduate Student Hiroshi Shimagami and Lecturer Masayuki Nishide from the Graduate School of Medicine at the University of Osaka announced that they have clarified the possibility of predicting "scleroderma renal crisis (SRC)" and "interstitial lung disease (ILD)" which are both life-threateningly severe cases of the designated intractable disease "systemic sclerosis (SSc)" that are difficult to diagnose in the early stages, through single-cell omics analysis of white blood cells. Blood analysis confirmed changes related to the monocyte lineage in SRC and the lymphocyte lineage in ILD. These results are expected to lead to early diagnosis and the development of treatment for these severe cases. The findings were published in the June 17 issue of Nature Communications.
SSc, systemic sclerosis; ILD, interstitial lung disease; WBC, white blood cells; ISG, interferon signature genes.
Provided by the University of Osaka
Systemic diseases caused by autoimmune abnormalities are called collagen diseases. SSc is one of these diseases with a poor life prognosis, but conditions vary greatly from patient to patient with considerable diversity.
There are approximately 25,000 patients with SSc in Japan. Almost all cases begin in the early stages with Raynaud's phenomenon, where blood flow to the fingertips deteriorates, followed by skin sclerosis. While some patients remain stable long-term without treatment, others who are positive for the same specific antibodies suddenly develop severe organ lesions, and the mechanism behind this was unknown. Cases involving fatal renal crisis or ILD pose challenges as early treatment selection is difficult.
In response, the research group applied omics analysis to patients' peripheral blood white blood cells to investigate the details of immune abnormalities underlying the diversity of symptoms in this disease.
First, when they compared monocytes from cases with and without SRC, they found that cases with SRC showed high expression of the transcription factor gene "EGR1," which is important for monocyte differentiation. When examining monocyte "EGR1" expression before and after onset of SRC and after treatment using patient blood, they confirmed that it increased immediately after onset and decreased after treatment.
Therefore, single-cell analysis and spatial transcriptome analysis were performed on renal tissue obtained from SRC patients together with monocytes.
As a result, the group confirmed that monocytes from SRC cases highly expressed EGR1, differentiated into macrophages that invaded the kidney and damaged tissue, and accumulated around injured tubular cells. This suggested the possibility of leading to severe renal dysfunction. It was also revealed that EGR1 could be used as a biomarker.
In cases of ILD, CD8-positive T cells activated by type II interferon increased in peripheral blood. Analyzing lung tissue data from patients showed the possibility that these cells migrate to diseased lung tissue through the action of chemokines.
Shimagami commented: "Going forward, based on these results, I would like to conduct research to predict the onset of SRC, a disease with many unexplained aspects. Currently, SRC is treated with medications that lower blood pressure and dilate blood vessels, but many patients with severe cases die. I would like to collect as many specimens as possible to verify these results and further analyze the relationship between kidney cells and macrophages."
Journal Information
Publication: Nature Communications
Title: Single-cell analysis reveals immune cell abnormalities underlying the clinical heterogeneity of patients with systemic sclerosis
DOI: 10.1038/s41467-025-60034-7
This article has been translated by JST with permission from The Science News Ltd. (https://sci-news.co.jp/). Unauthorized reproduction of the article and photographs is prohibited.