{
  "abstract": "Introduction CAR T-cell therapy targeting CD19 has shown potential in autoimmune diseases such as SSc, yet molecular profiling in these patients remains unexplored. In a phase 1 open-label trial ( NCT06414135), we assessed relmacabtagene autoleucel (relma-cel) in progressive diffuse cutaneous SSc. Relma-cel demonstrated a favorable safety profile across six patients. All patients achieved deep B-cell depletion, significant improvement in skin thickness scores, stabilization or improvement of interstitial lung disease, and marked reduction in autoantibody levels, indicating preliminary efficacy.Material and Methods We performed integrated single-cell RNA sequencing, T- and B-cell receptor repertoire analysis, plasma proteomics, and spatial transcriptomics at multiple timepoints to characterize molecular changes following CD19 CAR-T-mediated B-cell depletion in SSc patients.Results Single-cell RNA analysis of peripheral blood identified 7,486 B cells, subclustered into naïve B cells, memory B cells (switched and non-switched), age-associated B cells, and antibody-secreting cells. Naïve B-cell proportion increased by day 90 (D90), while plasma cell proportion was markedly reduced. Memory B cells (switched) decreased at D90 and partially recovered by D180, reflecting post-treatment immune remodeling. Gene set enrichment analysis revealed downregulation of B-cell activation, differentiation, and BCR signaling pathways by D180. IGHG and IGHA isotypes were largely eliminated post-treatment and did not return to baseline by D180. Clonal expansion and diversity among B-cell subtypes were reduced. Naïve T-cell proportions decreased at D90 and recovered by D180, whereas effector memory T cells showed the opposite trend. Skin endothelial cells exhibited reduced endothelial-mesenchymal transition signatures, and fibroblasts showed decreased collagen deposition signatures, aligning with clinical improvement.Plasma proteomics at D180 demonstrated significant reduction in markers linked to SSc skin progression, disease severity, and pulmonary fibrosis. GO and GSEA analyses indicated downregulation of extracellular matrix, immune, and inflammation-related pathways. Spatial transcriptomics identified a fibrosis-associated gene module—including collagens (COL1A1, COL1A2, COL3A1, COL6A1-3), ECM components (DCN, LUM, FN1, SPARC, BGN, CCN2), and activated fibroblast markers (SFRP2, COMP, POSTN)—whose expression was significantly reduced at D90 and further decreased at D180.Conclusions Our multi-omic analysis demonstrates that CD19 CAR-T cell therapy induces profound B-cell depletion and remodeling of the immune landscape in patients with progressive SSc. The observed reduction in pathogenic B-cell subsets, autoantibody production, and fibrotic gene module expression correlates with clinical improvements in skin and lung involvement. These findings suggest that CAR-T therapy may mitigate disease progression through coordinated modulation of adaptive immunity and fibroblast activation.Abstract P.247 Figure 1",
  "authors": [
    {
      "affiliations": [
        "Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China"
      ],
      "name": "Hanlin Yin"
    },
    {
      "affiliations": [
        "Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China"
      ],
      "name": "Zhangyi Zhao"
    },
    {
      "affiliations": [
        "Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China"
      ],
      "name": "Chenhan Jia"
    },
    {
      "affiliations": [
        "Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China"
      ],
      "name": "Wanyi Lin"
    },
    {
      "affiliations": [
        "Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China"
      ],
      "name": "Fenglin Wu"
    },
    {
      "affiliations": [
        "Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China"
      ],
      "name": "Zhe Ding"
    },
    {
      "affiliations": [
        "Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China"
      ],
      "name": "Xuesong Liu"
    },
    {
      "affiliations": [
        "Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China"
      ],
      "name": "Liangjing Lu"
    }
  ],
  "title": "P.247 Multi-omic profiling of patients with progressive systemic sclerosis undergoing CD19 CAR-T cell therapy",
  "uid": "6dd9a878-086d-556a-9be5-c675e7902aaf"
}