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The autoantibodies against the NR1 subunit are well known in the pathomechanism of NMDAR encephalitis. The dysfunction of the NR2 subunit could be a critical factor in this neurological disorder due to its important role in the postsynaptic pathways that direct synaptic plasticity. We report a case of paraneoplastic anti-NMDAR encephalitis presented alongside very severe illness. Computed tomography (CT) of the brain, as well as FLAIR and T2-weighted MRI, was performed to rule out any other acute brain processes. A semi-quantitative method was applied to detect the presence of anti-NMDAR antibodies in the serum and CSF. A CT chest–abdomen–pelvis scan was performed that detected an ovarian teratoma. A histopathological examination was performed after a laparoscopic right-ovary cystectomy. Subsequent immunofluorescence immunohistochemical staining showed the expression of NMDA receptors of type NR2B. Treatment included first-line immunotherapy, second-line immunotherapy, tumor removal, and intrathecal injections with methotrexate and dexamethasone. The histological finding for our patient after tumor removal was ovarian teratoma. Hematoxylin–eosin (HE) staining revealed a characteristic spectrum of elements, including stratified squamous epithelium and fat tissue accompanied by neuroglial cells. Subsequent immunohistochemical staining showed an expression of NMDA receptors of type NR2B in different structures of the teratoma, including the neuroglial cells. The first-line immunotherapy following the tumor removal was insufficient in our patient. The paraneoplastic anti-NMDAR encephalitis with a coexpressed NR2B subunit on the neural cells of the ovarian teratoma may suggest a different inflammation process and could be the key factor in the pathomechanism and treatment of the refractory anti-NMDAR encephalitis. Full article

Background/Objectives: Idecabtagene vicleucel (ide-cel), an anti-B-cell maturation chimeric antigen receptor T-cell therapy, represents an unprecedented treatment option for relapsed/refractory multiple myeloma (R/R MM). Nevertheless, given its limitations, including the risk of adverse effects and unclear durability of efficacy, there remains a need to report the real-world clinical outcomes of ide-cel therapy in patients with R/R MM, as well as explore host predictive factors for therapy. Methods: We performed a single-center retrospective analysis of 25 adult patients with R/R MM who received ide-cel between 2021 and 2023 at the University of California San Diego Health. Data on baseline characteristics, efficacy, safety, and post-relapse outcomes were collected. Treatment responses were assessed using the International Myeloma Working Group criteria while survival analyses were conducted using the Kaplan–Meier and Cox proportional hazards methods. Results: The median age was 65. Twelve patients (48%) were male. Patients received a median of six lines of prior therapy with four patients (16%) receiving prior BCMA-targeted therapy. Six patients (24%) had high-risk cytogenetics while ten patients (40%) had extramedullary disease. The incidence of cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome incidence was 92% and 12%, respectively. All grade infection occurred in 11 patients (44%). Cytomegalovirus (CMV) reactivation occurred in 9 of 19 patients (47%) who were CMV IgG positive prior to CAR T-cell therapy. The objective response rate (ORR) was 84%; stringent complete response was seen in 14 patients (56%). After a median follow-up of 13 months, median progression-free survival (PFS) was 13.9 months (95% CI: 9.21 months—not reached [NR]); median overall survival (OS) was not reached (95% CI: 19.5 months—NR). Among the 11 patients (44%) who progressed after ide-cel therapy, median OS2 was 13.7 months; especially poor outcomes (median OS2 of 1.74 months) were observed in four patients who did not respond to ide-cel. Six of these eleven patients remained alive at time of data cutoff. Univariate and multivariate analysis revealed no significant predictors of ORR, PFS, or OS. Conclusions: Overall, ide-cel had comparable efficacy and safety to the KarMMa-1 trial and other reported real-world experiences. Full article

Intra-renal tertiary lymphoid organs (TLOs) are associated with worsened outcome in kidney transplantation (Ktx). We used an anti-BAFF (B cell activating factor) intervention to investigate whether BAFF is required for TLO formation in a full MHC-mismatch Ktx model in rats. Rats received either therapeutic immunosuppression (no rejection, NR) or subtherapeutic immunosuppression (chronic rejection, CR) and were sacrificed on d56. One group additionally received an anti-BAFF antibody (CR + AB). Intra-renal T (CD3⁺) and B (CD20⁺) cells, their proliferation (Ki67⁺), and IgG⁺ plasma cells were analyzed by immunofluorescence microscopy. Formation of T and B cell zones and TLOs was assessed. Intra-renal expression of TLO-promoting factors, molecules of T:B crosstalk, and B cell differentiation was analyzed by qPCR. Intra-renal B and T cell zones and TLOs were detected in CR and were associated with elevated intra-renal mRNA expression of TLO-promoting factors, including CXCL13, CCL19, lymphotoxin-β, and BAFF. Intra-renal plasma cells were also elevated in CR. Anti-BAFF treatment significantly decreased intra-renal B cell zones and TLO, as well as intra-renal B cell-derived TLO-promoting factors and B cell differentiation markers. We conclude that BAFF-dependent intra-renal B cells promote TLO formation and advance local adaptive alloimmune responses in chronic rejection. Full article