Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Jul 22:S0003-4967(25)04187-1.
doi: 10.1016/j.ard.2025.06.2132. Online ahead of print.

Differential molecular signatures in response to CD19-CAR T cell therapy compared with conventional pharmacotherapy in systemic lupus erythematosus

Panagiotis Garantziotis  1 , Lorenzo Beretta  2 , Julius Lindblom  3 , Georgia-Savina Moysidou  4 , Dionysis Nikolopoulos  3 , Ricardo Grieshaber-Bouyer  1 , Melanie Hagen  1 , Christina Bergmann  1 , Andreas Wirsching  1 , Aline Bozec  1 ; PRECISESADS Clinical Consortium; Matthias Schneider  5 , Guillermo Barturen  6 , George Bertsias  7 , Dimitrios T Boumpas  4 , Marta E Alarcón-Riquelme  8 , Andreas Mackensen  9 , Georg Schett  10 , Ioannis Parodis  11
Affiliations

Differential molecular signatures in response to CD19-CAR T cell therapy compared with conventional pharmacotherapy in systemic lupus erythematosus

Panagiotis Garantziotis et al. Ann Rheum Dis. .

Abstract

Objectives: Early trials of CD19-chimeric antigen receptor (CAR) T cell therapy in systemic lupus erythematosus (SLE) show promise, but the molecular mechanisms underlying its disease-modifying effects remain unclear. We aimed to compare biological profiles and alterations following CD19-CAR T cell versus standard pharmacotherapy in SLE.

Methods: Pseudo-bulk gene expression derived from single-cell RNA sequencing of peripheral blood mononuclear cells from 7 SLE patients before and after CD19-CAR T cell therapy was compared with whole-blood transcriptome data from 30 SLE patients in remission on standard pharmacotherapy and 31 SLE patients before and 6 months after treatment with rituximab, belimumab, or cyclophosphamide. Pathway analysis was conducted using Functional Analysis of Individual Microarray Expression and gene set enrichment analysis.

Results: CD19-CAR T cell-induced remission was characterised by marked suppression of complement activation, type I interferon, DNA damage response (DDR), and cell death pathways compared with remission following conventional pharmacotherapy, alongside an upregulation of lipid metabolism pathways. Compared with rituximab and belimumab, CD19-CAR T cell therapy induced greater downregulation of type I/II interferon, DDR, and chemokine pathways. Compared with cyclophosphamide, CD19-CAR T cell therapy induced greater suppression of interferon, mitochondrial, and mammalian target of rapamycin signalling pathways.

Conclusions: CD19-CAR T cell therapy induces substantial suppression of key immunological pathways involved in SLE, including complement activation and type I interferon responses, accompanied by a metabolic reprogramming. Molecular profiles of remission after CD19-CAR T cell therapy differ from those induced by conventional SLE pharmacotherapy, suggesting more profound CD19-CAR T cell-induced biological alterations.

PubMed Disclaimer

Conflict of interest statement

Competing interests GS has received speaker honoraria from BMS, Cabaletta, Janssen, Kyverna, Miltenyi, and Novartis. IP has received research funding and/or honoraria from Amgen, AstraZeneca, Aurinia, BMS, Elli Lilly, Gilead, GSK, Janssen, Novartis, Otsuka, and Roche. The other authors declare no conflicts of interest. The funders had no role in the design of the study, in the collection, analyses, or interpretation of data, in the writing of the manuscript, or in the decision to publish the results.