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Journal of Experimental Medicine

Researchers at the University of Osaka uncover early changes seen in ANCA-associated glomerulonephritis and investigate a treatment to stop it in its tracks

Fig1: Neutrophil–epithelial niches in the kidney in ANCA-associated vasculitis
A spatial transcriptomic cell map showing neutrophils (pink) accumulating around injured proximal tubular epithelial cells (yellow), forming a local pathogenic microenvironment termed a “neutrophil–epithelial niche.” Other colors represent other renal and immune cell populations.
Credit: Masayuki Nishide

Osaka, Japan – When immunity works well, the body steers clear of infection and disease. However, when the immune system goes awry, healthy cells can often end up in the firing line. This can occur in autoimmune diseases like anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis, a kidney disease in which ANCAs trigger destructive inflammation. However, there has been little information about the sequence of events associated with the early stages of disease.
Now, researchers from the University of Osaka have uncovered the first steps in the development of ANCA-associated glomerulonephritis. The researchers found that injured kidney cells send signals that attract immune cells, including neutrophils, which drive the spread of inflammation in the early stages. The findings were published this month in the Journal of Experimental Medicine.
Despite improvement in treatment options, current treatments for ANCA-associated glomerulonephritis carry risks ranging from side effects of prolonged use to treatment failure. Targeted treatments could offer better health outcomes for patients. However, to do so, researchers would need to clarify how the disease process starts to tackle the problems head on.
“In ANCA-associated glomerulonephritis, the kidneys are frequently involved,” explains lead author, Masayuki Nishide. “This makes it an excellent candidate for studying the initial steps of the autoimmune disease process.”
The researchers compared kidney samples from healthy donors and from patients with ANCA-associated glomerulonephritis who did not receive treatment. Using cutting-edge technology, they studied the sequence of events in disease progression while preserving cellular organization in the tissue samples.
“Our goal was to investigate how exactly the disease unfolds in the early stage so that we could attempt to stop it before significant damage is done,” says senior author, Atsushi Kumanogoh. “We were surprised to see that despite the normal appearance of the tissue, we could still detect changes at the cellular level.”
After finding that diseased organs displayed more damage compared to normal kidneys, the researchers aimed to replicate and treat the injury using a mouse model. The researchers found that excessive neutrophil activation is a key aspect of early disease, leading researchers to attempt to decrease neutrophil activation. In turn, researchers modified antibodies and tested whether they could minimize stimulation of Fcγ receptors, which are integral to the development of the inflammatory process.
The results were promising, and the modified antibodies successfully reduced kidney injury in the model. These findings point to a potential new therapeutic strategy aimed at stopping the disease at its earliest stage, before severe kidney damage develops. It is hoped that continued developments in this area can offer patients new hope for potentially safer treatments with fewer side effects.

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The article, “Epitope-diverse autoantibodies induce neutrophil–epithelial niches driving kidney injury in ANCA–associated glomerulonephritis,” will be published in the Journal of Experimental Medicine at DOI: https://doi.org/10.1084/jem.20260506

Summary:
Researchers from the University of Osaka uncovered the first steps of disease development in ANCA-associated autoimmune glomerulonephritis. Injured kidney cells send signals to attract immune cells, including neutrophils, and induce inflammation. The researchers tested the effects of modified antibodies on halting disease progression in a mouse model, showing that the modified antibodies successfully reduced kidney injury. The findings offer hope for a potential treatment aimed at stopping the disease at its earliest stage.

Tweet 1:Investigating drivers of early kidney disease: @UOsaka researchers highlight new discoveries about ANCA-associated autoimmune kidney disease
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Primary Keyword: Health and medicine

Additional Keywords: Autoimmune disorders, nephritis, disease progression, pathophysiology, pathogenesis, autoantibodies, epitopes, monoclonal antibodies, immunotherapy

Title:Epitope-diverse autoantibodies induce neutrophil–epithelial niches driving kidney injury in ANCA-associated glomerulonephritis

Journal:Journal of Experimental Medicine

Authors:Masayuki Nishide, Hiroaki Matsushita, Yumiko Mizuno, Kei Nishimura, Patrick M Lelliott, Shoji Kawada, Takashi Fujii, Shogo Kamikawaji, Tatsuya Nonaka, Daisuke Motooka, Shoichi Metsugi, Hiroshi Shimagami, Atsuko Tsujii Miyamoto, Yasuhiro Kato, Kohei Tsujimoto, Ryuya Edahiro, Yuya Shirai, Yuji Yamamoto, Yujiro Naito, Hachiro Konaka, Mayuko Izumi, Maiko Naito, Yoshimitsu Nakanishi, Tomoko Namba-Hamano, Kazunori Inoue, Atsushi Takahashi, Masayuki Mizui, Shigeaki Nakazawa, Yoichi Kakuta, Kenji Funakoshi, Makoto Terada, Machiko Irie, Takuya Torizawa, Ryusuke Omiya, Nicolas I Smith, Yoshitaka Isaka, Norio Nonomura, Yukinori Okada, Kunihiro Hattori, Masashi Narazaki, Atsushi Kumanogoh

DOI:10.1084/jem.20260506

Funded by:
Japan Society for the Promotion of Science
Japan Agency for Medical Research and Development
Japan Science and Technology Agency

Conflicts of Interest statement:
This study involved collaboration with Chugai Pharmaceutical Co., Ltd. Several co-authors are employees of and shareholders in Chugai Pharmaceutical Co., Ltd., and Atsushi Kumanogoh has received grant support from the company.

Article publication date:19-OCT-2026

Related links:
Masayuki Nishide
https://rd.iai.osaka-u.ac.jp/en/6cfaf6f4c063e89c.html
Masashi Narazaki
https://rd.iai.osaka-u.ac.jp/en/55ca1ee01bb8f983.html
Atsushi Kumanogoh
https://rd.iai.osaka-u.ac.jp/en/cf8a0b39aebc617f.html

Method of Research:Experimental study

Subject of Research:Human tissue samples