This study investigates the role of B and T cells in kidney biopsies from patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), an autoimmune disease that primarily affects small blood vessels, leading to severe complications in organs such as the lungs and kidneys. In AAV, the immune system mistakenly attacks the body’s own tissues, and B cells, a type of white blood cell responsible for producing antibodies, are known to play a key role in this process. This is evident from the clinical benefits of treatments like rituximab, which specifically targets B cells. However, most studies on B and T cells in AAV focus on the peripheral blood (the blood circulating in the body), and little is known about how these cells behave in the kidneys, which are often severely affected by the disease.
The aim of this study was to profile B and T cells at the single-cell level in kidney biopsies from AAV patients with glomerulonephritis (inflammation of the kidney’s filtering units, called glomeruli), as well as in a control patient who had undergone a nephrectomy (kidney removal). By using advanced techniques to analyze cells from these biopsies, the researchers sought to better understand how B and T cells contribute to kidney damage in AAV patients.
Methods:
The researchers collected kidney biopsies from four AAV patients with active glomerulonephritis and a nephrectomy control. They isolated live CD45+ immune cells (a marker found on most immune cells) from the kidney tissue and processed these cells for single-cell analysis. This method allows the study of individual cells, providing a more detailed understanding of the immune cell populations present. The data was compared to a reference map of immune cells in the kidney, called the mature immune kidney cell atlas.
Results:
In their analysis, the researchers identified 24 clusters of immune cells, with a particular focus on B and T cells, which are central to adaptive immunity (the immune system’s ability to recognize and remember specific pathogens). Two of these clusters were enriched in B cells, identified by the expression of CD19 and CD20 (markers specific to B cells), which made up about 5.07% of the total cells. Additionally, they found a smaller cluster of plasmablasts and plasma cells (cells that produce antibodies), representing 0.45% of the total.
The B cell population was further divided into four subgroups:
• Memory B cells (51.20%), which help the immune system remember past infections.
• Naïve B cells (38.72%), which have not yet encountered a pathogen.
• Plasmablast-like cells (5.24%), which are immature cells on their way to becoming plasma cells.
• Plasma cells (4.85%), which produce antibodies to fight infections.
At a higher resolution, they identified even more detailed subtypes of these B cells, including three different types of memory B cells and three types of naïve or germinal center-like B cells. These detailed distinctions could help researchers understand how different types of B cells contribute to kidney damage in AAV.
For T cells, which made up 61.35% of the immune cells in the biopsies, they identified 11 clusters. T cells are typically divided into CD4 T cells (which help activate other immune cells) and CD8 T cells (which can directly kill infected or damaged cells). The researchers found four CD4 T cell clusters and four CD8 T cell clusters. At higher resolution, they identified eight subtypes of CD4 T cells, including a regulatory T cell (Treg) cluster, which helps prevent the immune system from attacking the body’s own tissues, and a helper T cell-like cluster, which is involved in activating other immune cells. They also found eight subtypes of CD8 T cells, including a subset called TEMRA cells, which are known for their ability to kill infected or damaged cells. Additionally, they identified three clusters of natural killer (NK) cells, which are part of the body’s innate immune system.
Conclusion:
This study provides a detailed profile of B and T cell populations in the kidneys of AAV patients with glomerulonephritis, offering new insights into the immune mechanisms that may drive kidney damage in this disease. The identification of specific subtypes of B and T cells, along with their associated gene expression patterns, could help uncover new therapeutic targets for AAV. For example, targeting certain B cell subtypes or specific signaling pathways involved in T cell activation could lead to more effective treatments for patients with AAV-related kidney damage. This study represents a significant step toward understanding the immune landscape in the kidneys of AAV patients, moving beyond blood-based studies to investigate the immune cells directly within the affected organ.