医学
自身抗体
免疫学
蛋白酶3
显微镜下多血管炎
髓过氧化物酶
细胞毒性T细胞
骨髓
抗原
抗体
血管炎
生物
病理
炎症
生物化学
疾病
体外
作者
Dörte Lodka,Maria Zschummel,Mario Bunse,Anthony Rousselle,Janis Sonnemann,Ralph Kettritz,Uta E. Höpken,Adrian Schreiber
出处
期刊:PubMed
日期:2024-01-05
标识
DOI:10.1136/ard-2023-224875
摘要
Anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitides (AAV) are life-threatening systemic autoimmune diseases manifesting in the kidneys as necrotizing crescentic glomerulonephritis (NCGN). ANCA antigens are myeloperoxidase (MPO) or proteinase 3. Current treatments include steroids, cytotoxic drugs and B cell-depleting antibodies. The use of chimeric antigen receptor (CAR) T cells in autoimmune diseases is a promising new therapeutic approach. We tested the hypothesis that CAR T cells targeting CD19 deplete B cells, including MPO-ANCA-producing B cells, thereby protecting from ANCA-induced NCGN.We tested this hypothesis in a preclinical MPO-AAV mouse model. NCGN was established by immunisation of MPO-/- mice with murine MPO, followed by irradiation and transplantation with haematopoietic cells from wild-type mice alone or together with either CD19-targeting CAR T cells or control CAR T cells.CD19 CAR T cells efficiently migrated to and persisted in bone marrow, spleen, peripheral blood and kidneys for up to 8 weeks. CD19 CAR T cells, but not control CAR T cells, depleted B cells and plasmablasts, enhanced the MPO-ANCA decline, and most importantly protected from NCGN.Our proof-of-principle study may encourage further exploration of CAR T cells as a treatment for ANCA-vasculitis patients with the goal of drug-free remission.
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