Abstract: TH-PO0427
Myeloperoxidase-Specific B Cells from Patients with ANCA Have Distinct Immunophenotypes and B-Cell Receptors (BCRs) in Active Disease Compared with Long-Term Remission Off Therapy
Session Information
- Glomerular Diseases: Autoimmune Diseases
October 22, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology
Authors
- Lakshmanan, Arjun, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
- Gomez-Martinez, Ismael, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
- Moon, Young-Hyun, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
- Taylor, Justin J., University of Virginia Beirne B Carter Center for Immunology Research, Charlottesville, Virginia, United States
- Falk, Ronald, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
- Bunch, Donna O., The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
- Chen, Dhruti P., The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
Background
Autoantigen-specific B cells are key drivers of myeloperoxidase (MPO) -Anti-Neutrophil Cytoplasmic Autoantibody (ANCA) Vasculitis. We hypothesized that key cell types and pathways in the MPO-specific B cell population differentiate active disease vs long term remission off therapy (LTROT). Ours is the first study to test this hypothesis by combined transcriptomic immunophenotyping and paired BCR data from isolated MPO-specific B cells.
Methods
Peripheral blood mononuclear cells from 3 patients with active MPO-ANCA, 3 LTROT patients, and 3 healthy controls (HC) were used with validated MPO tetramers to enrich and sort MPO-specific B-cells (TPOS). Control tetramers without MPO were used to exclude cells with non-specific tetramer reactivity. Single-cell gene expression and V(D)J libraries were generated with 10x Genomics Chromium Single Cell 5′ platform. Single-cell RNA sequencing and B-cell receptor sequencing data were analyzed with Seurat (v5.4.0).
Results
A total of 26,063 B cells were sequenced, 1,013 of which were TPOS. Patients had an average of 5% TPOS comparable to prior assays. In MPO-ANCA specific B cells, a majority were plasma cells (60.3%) in active patients but not in LTROT (2.3%) or HC (2.9%). Remission and HC samples were enriched for naïve and memory B cells. Heavy-chain composition in TPOS B cells differed across groups, with active disease showing a greater representation of class-switched IgG and IgA BCRs (Figure), LTROT patients had an increased IgM population, and HC had the largest IgD population. In comparing active patients to remission or HC, gene set enrichment analysis revealed metabolically active pathways including oxidative phosphorylation, glycolysis, and endoplasmic reticulum stress response.
Conclusion
Single cell profiling of MPO-specific B cells shows disease-associated differences in BCRs (increased IgA in active diseae vs. IgM in LTROT) and transcriptional immunophenotype in MPO-ANCA . This foundational data will inform additional studies to identify immunomic differences associated wtih LTROT.
Funding
- Other NIH Support