Neutrophils, one of the immune system warriors that were thought to be all the same, turn out to be diverse. Unfortunately, these cells are also active in autoimmune diseases. New research from Japan has found that a certain subpopulation of these white blood cells can predict disease relapse at an early stage, which may enable improved personalized treatment.

In a study soon to be published in Nature Communications, a multi-institutional research team led by The University of Osaka investigated which cell types dominate the blood of patients at the early stage of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, which is caused by inflammation in the blood vessels and can disrupt organ function.

“Figuring out the mechanism of this disease, which is poorly understood, will help us understand autoimmune dysregulation in neutrophils. This could aid in the development of new drugs tailored for each patient,” says lead author of the study Masayuki Nishide. “Because we want to understand the dynamics of neutrophil behavior at the cell level in the early stages of the disease, for this study we recruited new patients that had not yet been treated.”

The team recruited six patients and seven healthy people for comparison. They collected approximately 180,000 white blood cells and performed single-cell analyses to characterize them genetically, as well as looking at the proteins on the cell surface. These transcriptome and proteome analyses revealed significantly higher proportions of two specific neutrophil subpopulations in the patients, compared with the healthy individuals.

“We were intrigued to discover an increase in a highly activatable subset of neutrophils in these patients. These neutrophils can be stimulated by interferon-gamma (IFN-g), an important inflammation protein,” explains Atsushi Kumanogoh, senior author. “Three of the patients who showed the highest expression of IFN-g response genes also had persistent vasculitis symptoms following treatment, which tells us that this neutrophil subpopulation is involved in stubborn vasculitis.”

These results led the team to measure the amount of IFN-g in stored serum samples from 37 patients, some of whom were newly diagnosed and some who had undergone treatment. “The results were striking, as among 24 new-onset patients assessed, the top six patients with the highest serum IFN-g concentrations all experienced relapses, indicating that measuring the concentration of IFN-g in the blood could help us predict disease relapse,” says Nishide.

This research significantly enhances our understanding of the immune mechanisms driving ANCA-associated vasculitis and opens the door to new approaches for disease monitoring and therapy. By identifying specific neutrophil populations and their roles in disease progression, these findings could lead to more personalized treatment strategies and better outcomes for patients battling this rare but severe condition.