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Researchers at University of Tsukuba and the Japan Research Committee of the Ministry of Health, Labour, and Welfare for Intractable Vasculitis have identified genetic factors associated with eosinophilic granulomatosis with polyangiitis (EGPA), a rare systemic inflammatory disease and a designated intractable disease in Japan. Their findings suggest that a variant in the thymic stromal lymphopoietin (TSLP) gene increases disease susceptibility in Japanese and European populations, whereas specific HLA-DRB1 variants influence disease risk differently across populations. The study provides new insights into the genetic architecture of EGPA and advances our understanding of disease mechanisms in East Asian populations.

Tsukuba, Japan—Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic inflammatory disease characterized by eosinophilia, an abnormal increase in eosinophils—a type of white blood cell—and inflammation of the small blood vessels across multiple organs, which can lead to organ damage. This disease is often preceded by asthma or chronic rhinosinusitis and has been designated as an intractable disease in Japan. Genetic factors appear to contribute to disease susceptibility and development. Previous genome-wide association studies, conducted primarily in European populations, have identified several genetic variants associated with susceptibility to EGPA. However, the genetic basis for EGPA among East Asian populations has remained largely unexplored.

In this study, the researchers investigated whether genetic variants previously reported to be associated with EGPA in European populations also increase disease susceptibility in Japanese individuals with EGPA.

The results suggest that a variant in the thymic stromal lymphopoietin (TSLP) gene may be associated with susceptibility to EGPA among both Japanese and European populations. TSLP encodes a cytokine produced primarily by epithelial cells lining the airways, gastrointestinal tract, and other barrier tissues, where it plays an important role in allergic inflammation.

The researchers also examined the involvement of HLA-DRB1, one of the HLA genes that play a central role in antigen presentation and immune responses, in disease susceptibility. Among the various HLA-DRB1 alleles analyzed, DRB1*07:01 was associated with EGPA among both Japanese and European populations, whereas DRB1*09:01 was associated with EGPA only in the Japanese population.

These results indicate that the genetic architecture underlying EGPA involves both susceptibility factors shared across populations and population-specific genetic factors. Together, these findings deepen our understanding of the pathogenesis of EGPA and may guide future studies aimed at improving the diagnosis and treatment of the disease.

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This work was supported by the grants from the Japan Agency for Medical Research and Development "The Study Group for Strategic Exploration of Drug Seeds for ANCA Associated Vasculitis and Construction of Clinical Evidence [grant number 17ek0109104h0003]", "The Strategic Study Group to Establish the Evidence for Intractable Vasculitis Guideline [grant number 17ek0109121h0003]", and "Multitiered study to address clinical questions for management of intractable vasculitides [grant number 20ek0109360h0003]", Ministry of Health, Labour and Welfare [grant number JPMH20FC1044, JPMH23FC1019 and JPMH26FC1018], Japan Society for the Promotion of Science KAKENHI [grant number JP17K09967, JP21K08435, JP25K11700], research grants from Bristol-Myers Squibb K.K., Takeda Science Foundation, the Uehara Memorial Foundation, Japan Rheumatism Foundation, Ichiro Kanehara Foundation, collaborative research fund from H.U. Group Research Institute G.K., and award grants from Japan College of Rheumatology and Japan Rheumatism Foundation.

Original Paper

Title of original paper:

Genetic associations of eosinophilic granulomatosis with polyangiitis in the Japanese population: Exploring similarities and differences with European populations

Journal:

RMD Open

DOI:

10.1136/rmdopen-2025-006644

Correspondence

Assistant Professor KAWASAKI Aya
Institute of Medicine, University of Tsukuba

Professor and Chairman TAMURA Naoto
Department of Internal Medicine and Rheumatology, Juntendo University Faculty of Medicine

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