case_images: PMC10762793_01
case_images: Flow chart of the treatment schedule from the diagnosis of SjD and DLBCL to CAR-T cell therapy. (A) Number of circulating CAR-T cells assessed via flow cytometry from day 0 to day 90 after CAR-T cell therapy. (B) Changes in the levels of five types of cytokines from day 0 to day 90 after CAR-T cell therapy assessed using a human cytokine detection kit with flow cytometry (Qingdao Raisecare Biotechnology). (C) PET-CT images before and 28 days after CAR-T cell infusion. (D) Changes in chest CT findings before and after CAR-T cell infusion (E). The white arrow indicates the location of the retroperitoneal lesion. *: Lenalidomide was administered at a dose of 25 mg/day for 1-10 days per month during 79-89 months. #: Supportive care: intermittent transfusion of platelets and other blood products. SjD: Sjogren's disease; DLBCL, diffuse large B-cell lymphoma; R-CHOP, rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone; CR, complete response; PD, progressive disease; PR: partial response; CAR-T, chimeric antigen receptor-T cell; ICE, ifosfamide, carboplatin, and etoposide; IL, interleukin; TNF, tumor necrosis factor; IFN-gamma, interferon gamma; IVIG, intravenous immunoglobulin.
case_images: fimmu-14-1298815-g001.jpg
case_images: PMC10762793_01_fimmu-14-1298815-g001.jpg
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case_images:   Figure 1A  shows the treatment schedule of the patient. C on day 4. Cytometry assay revealed gradually increasing levels of numerous cytokines along with an abundance of CAR-T cells ( Figures 1B, C ). To manage CRS, the first dose of tocilizumab (8 mg/kg) was prescribed on the same day ( Figure 1A ); however, her fever remained uncontrolled. Deaville's score was 2, indicating CR ( Figure 1D ). Moreover, significant improvement was observed in the pulmonary interstitium ( Figure 1E ).
case_images: Levels of ANA and Ro-52 (A), cytokines (B), and lymphocyte subsets (including absolute values and percentage values for each lymphocyte subset over all lymphocytes in the patients' peripheral blood) (C) before DLBCL diagnosis; before CAR-T therapy; and on days 30, 90, and 180 after CAR-T therapy. Dashed lines in (B) and (C) indicate normal ranges of cytokines and lymphocyte subsets. ANA, antinuclear autoantibodies; DLBCL, diffuse large B-cell lymphoma; CAR-T, chimeric antigen receptor-T cell; IL, interleukin; TNF, tumor necrosis factor; IFN-gamma, interferon gamma.
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case_images: PMC10762793_01_fimmu-14-1298815-g002.jpg
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case_images: Surprisingly, throughout her 10-year SjD history, she was negative for ANAs and anti-Ro-52 for the first time on day 90 after CAR-T cell infusion ( Figure 2A ). Approximately 1 month after infusion, cytokines gradually decreased to normal levels prior to CAR-T treatment ( Figure 2B ), which was considered to be partially due to the control of the autoimmune disease by CAR-T treatment, although the potential contribution of tocilizumab, methylprednisolone, IVIG treatment, and lymphodepletion cannot be excluded. Her peripheral blood lymphocytes were also monitored, and changes in CD4+, CD8+, and memory Th cells were observed, consistent with the outcomes of SjD management ( Figure 2C ). Suppressing CD4+ T cells can consequently inhibit abnormal B-cell activation and reduce disease activity.  Figure 2B  shows the changes in the numbers of lymphocyte subsets during the treatment period, including the marked increase in the number of CD8+ lymphocytes after treatment.