Fcγ-receptor-activation by circulating immune complexes in systemic autoimmune diseases and its reduction by CD19-CAR T cell therapy.
Objectives The role of autoantibody-producing B cells in connective tissue diseases (CTD) has recently been highlighted by the successful treatment with CD19-targeting CAR T cells. Detrimental effects of autoantibodies are linked to the formation of deposited IgG complexes and the activation of immu...
| Published in: | Rheumatology Vol. 65; no. 3; pp. 1 - 11 |
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| Main Authors: | , , , , , , , , , |
| Format: | pictorial research tables/charts Journal Article |
| Published: |
Oxford University Press / USA
Mar2026
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| Online Access: | View this record in EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=192667737&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 192667737 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 14620324 DN9 jtl: Rheumatology issn: 14620324 maglogo: N pubinfo: dt: Mar2026 vid: 65 iid: 3 pid: 622 pub: Oxford University Press / USA artinfo: ui: 192667737 192667737 192667737 10.1093/rheumatology/keaf627 192667737 ppf: 1 ppct: 10 formats: tig: atl: Fcγ-receptor-activation by circulating immune complexes in systemic autoimmune diseases and its reduction by CD19-CAR T cell therapy. aug: au: Freitag, Merle Kolb, Philipp Falcone, Valeria Claus, Maren Schröder, Pauline Andreeva, Ivana Rodon, Lea Ewald, Meike Deicher, Franca Sophie Stütz, Ayla Nadja affil: Department of Hematology, Oncology and Rheumatology, Internal Medicine V, University Hospital Heidelberg, Heidelberg, Germany sug: subj: Autoimmune Diseases Immunology Immunotherapy Receptors, Immunologic Connective Tissue Diseases Immunology Human Funding Source Female Male Adolescence Adult Middle Age Aged Aged, 80 and Over Cross Sectional Studies Prospective Studies Descriptive Statistics Data Analysis Software Mann-Whitney U Test Kruskal-Wallis Test Chi Square Test Spearman's Rank Correlation Coefficient Multiple Linear Regression Flow Cytometry Sjogren's Syndrome Lung Diseases, Interstitial Autoantibodies Immunology Adolescent: 13-18 years Adult: 19-44 years Middle Aged: 45-64 years Aged: 65+ years Aged, 80 & over Female Male ab: Objectives The role of autoantibody-producing B cells in connective tissue diseases (CTD) has recently been highlighted by the successful treatment with CD19-targeting CAR T cells. Detrimental effects of autoantibodies are linked to the formation of deposited IgG complexes and the activation of immune cells via Fcγ receptors (FcγRs). The role of circulating immune complexes (cICs) as a link between adaptive and innate immunity has remained understudied. Clinical testing of cICs has been hindered by the lack of reliable detection methods. The aim of this study was to determine the potential of IgG-containing cICs to activate FcγRs (their bioactivity) using a new detection method. Methods A reporter cell platform was used to assess the presence and bioactivity of cICs in IgG-autoantibody-positive CTD patients (cross-section analysis) and in patients treated with CD19-CAR T cells (longitudinal analysis). Results The bioactivity of cICs in the cohort of patients with CTDs was significantly higher compared with healthy controls and patients with IgG-autoantibody-negative systemic inflammatory disease (psoriatic arthritis). Analyses of individual diseases revealed the presence of cICs in the sera of all CTDs, including systemic sclerosis (SSc) and primary Sjögren's syndrome, although there was significant heterogeneity among individuals. Within SSc, patients positive for anti-topoisomerase-I (Scl70) autoantibodies, diffuse cutaneous and lung involvement had significantly enhanced cIC bioactivity. Finally, the bioactivity of cICs was significantly reduced in CTD patients after CD19-CAR T cell therapy. Conclusions Our study reveals the presence of FcγR-engaging cICs in CTDs and demonstrates that the bioactivity of cICs is correlated with clinical phenotypes and treatment outcomes. pubtype: Academic Journal doctype: pictorial research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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