Immunological effects of CD19.CAR-T cell therapy in systemic sclerosis

• Verfasst von: Claus, Maren [VerfasserIn]
• Verfasst von: Freitag, Merle [VerfasserIn]
• Verfasst von: Ewald, Meike [VerfasserIn]
• Verfasst von: Rodon, Lea [VerfasserIn]
• Verfasst von: Deicher, Franca [VerfasserIn]
• Verfasst von: Watzl, Carsten [VerfasserIn]
• Verfasst von: Kolb, Philipp Leonhard [VerfasserIn]
• Verfasst von: Lorenz, Hanns-Martin [VerfasserIn]
• Verfasst von: Schmitt, Michael [VerfasserIn]
• Verfasst von: Merkt, Wolfgang [VerfasserIn]
• Titel: Immunological effects of CD19.CAR-T cell therapy in systemic sclerosis
• Titelzusatz: an extended case study
• Verf.angabe: Maren Claus, Merle Freitag, Meike Ewald, Lea Rodon, Franca Deicher, Carsten Watzl, Philipp Kolb, Hanns-Martin Lorenz, Michael Schmitt, Wolfgang Merkt
• E-Jahr: 2024
• Jahr: 13 December 2024
• Umfang: 8 S.
• Illustrationen: Illustrationen
• Fussnoten: Gesehen am 21.03.2025
• Titel Quelle: Enthalten in: Arthritis Research & Therapy
• Ort Quelle: London : BioMed Central, 1999
• Jahr Quelle: 2024
• Band/Heft Quelle: 26(2024), Artikel-ID 211, Seite 1-8
• ISSN Quelle: 1465-9913
• ISSN Quelle: 1478-6362
• DOI: doi:10.1186/s13075-024-03451-1
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: CAR-T cell therapy
• Sach-SW: Fcγ receptor
• Sach-SW: NK cells
• Sach-SW: NKG2A
• Sach-SW: Pulmonary fibrosis
• Sach-SW: Systemic sclerosis
• K10plus-PPN: 1920333622

Abstract

Objective: The high potential of CD19.CAR-T cells to treat autoimmune diseases such as Systemic Sclerosis (SSc) supposedly relies on the disappearance of autoantibodies. Here we investigated effects of CAR-T cells on the innate immune system which is an important contributor to pathology in SSc. Methods: Longitudinal analysis of peripheral blood mononuclear cells from an Scl70 + SSc patient treated with CAR-T cells sampled over 18 months by 29-color spectral flow cytometry, in vitro experiments using sera from patient cohorts. Results: In the patient treated with CAR-T cells, the substantial clinical improvement was paralleled by dynamic changes in innate lymphoid cells, namely Fcγ-receptor IIIA-expressing natural killer (NK) cells. NK cells adopted a more juvenile, less activated, and less differentiated phenotype. In parallel, the potency of serum to form Scl70-containing immune complexes that activate Fcγ-receptor IIIA decreased over time. These observations suggested a mechanistic link between reversal of adaptive autoimmunity and recovering Fcγ-receptor IIIA-expressing innate immune cells after CAR-T cell therapy via regressing immune complex activity. Experiments with sera from the non-CAR-T-treated SSc cohort confirmed that Scl70-containing immune complexes activate Fcγ-receptor IIIA-expressing NK cells in a dose-dependent manner, substantiating the relevance of this link between adaptive and innate immunity in SSc. Conclusion: This report describes for the first time the phenotypic recovery of innate Fcγ-receptor-expressing cells in an SSc patient treated with CAR-T cells. Decreasing autoantibody levels associated with a reduced ability to form functional immune complexes, the latter appearing to contribute to pathology in SSc via activation of Fcγ receptor IIIA + cells such as NK cells.