The short‐term efficacy of combined treatments targeting B cell and plasma cell in severe and refractory Anti‐N‐methyl‐D‐aspartate receptor encephalitis: Two case reports

Zhang, Xiaoting; Wang, Chunjuan; Wang, Baojie

doi:10.1111/cns.13078

Cited by 12 publications

(8 citation statements)

References 10 publications

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“…A small number of patients received second-line treatment, including those with unsatisfactory or relapsed after receiving first-line immunotherapy. Previous studies have suggested that the onset of anti-NMDAR encephalitis is closely related to B cell immunity, and the therapeutic mechanism of rituximab depends on the depletion of B cells (21,22). However, only sporadic case reports support these findings, and no large-scale studies have been conducted.…”

Section: Discussionmentioning

confidence: 97%

Characteristics and Prognosis of Autoimmune Encephalitis in the East of China: A Multi-Center Study

Qiao

Liu

et al. 2021

Front. Neurol.

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Objective: This study aimed to investigate epidemiological characteristics, clinical manifestations, and long-term outcomes of patients with autoimmune encephalitis (AE) in the east of China.Methods: From January 2015 to December 2019, 226 potential AE patients were recruited from five clinical centers, and a total of 185 patients who met the diagnostic criteria were included in the study. We retrospectively reviewed clinical features, auxiliary examinations, details of treatments, and outcomes of AE, and identified risk factors of poor prognosis. Modified Rankin Scale scores were used to evaluate neurological function, and scores of 3–6 indicated a poor-prognosis.Results: Patients with five main subtypes of AE were enrolled in the study, as follows: anti-NMDAR (79), anti-LGI1 (55), anti-CASPR2 (30), anti-GABABR (16), and anti-AMPAR (5). Among 185 patients, 58.38% (108/185) were male and 41.62% (77/185) were female. The median age at disease onset was 41 years (interquartile range, 17–62). The most common clinical manifestations of AE were seizures (146, 78.92%) and memory deficit (123, 66.49%). A total of 95 (51.35%) patients had abnormal brain magnetic resonance imaging results. Electroencephalographic findings were abnormal in 131 (70.81%) patients, and 168 (90.81%) and 26 (14.05%) patients were treated with first- and second-line immunotherapies, respectively. All surviving patients were followed-up for at least 1 year (range 12–36 months). Good clinical outcomes were achieved in 117 (63.24%), while 68 (36.76%) patients had a poor prognosis. Further, 33 (17.84%) patients relapsed and 10 (5.41%) died within 1 year post-discharge. Older patients tended to have a poorer prognosis, and the occurrence of mental behavioral disorders, movement disorders, disturbance of consciousness, central hypoventilation, and tumors were overrepresented in the poor-prognosis group.Conclusions: AE is a treatable disease, and most patients have a good prognosis. There are differences in the clinical manifestations of patients with different AE subtypes. Some with AE will relapse, and long-term follow-up is of great significance for further research.

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Section: Discussionmentioning

confidence: 97%

Characteristics and Prognosis of Autoimmune Encephalitis in the East of China: A Multi-Center Study

Qiao

Liu

et al. 2021

Front. Neurol.

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“… 26 B cell-targeting therapies, including RTX, are effective in anti-NMDAR encephalitis, especially in recurrent and severe patients. 6 These results illustrate an important immunoregulatory role for B cells in the pathogenesis of anti-NMDAR encephalitis. In the current study, the percentage of B cells (CD3-CD19+) was higher in the anti-NMDAR encephalitis group than in the control group, and the protein level of syncytin-1 in serum of patients with anti-NMDAR encephalitis positively correlated with the proportion of B cells.…”

Section: Discussionmentioning

confidence: 77%

“…The pathogenesis of anti-NMDAR encephalitis is considered to be predominantly mediated by humoral immunity and B lymphocytes. 5 , 6 In recent years, “B-lymphocyte depletion” therapy, such as rituximab (RTX), has achieved good results in anti-NMDAR encephalitis patients, confirming the important role of B lymphocytes in the development of this disease. 7 Additionally, the peripheral blood T cell subsets of patients may be able to serve as an indicator of the disease process in anti-NMDAR encephalitis and may contribute to its pathogenesis.…”

Section: Introductionmentioning

confidence: 99%

Role of Increased Syncytin-1 Expression in Pathogenesis of Anti-N-Methyl-d-Aspartate Receptor Encephalitis

Qiao¹,

Sun²,

Zhang³

et al. 2022

NDT

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Purpose Syncytin-1 may play a role in several neuropsychiatric disorders, but its function in anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is unknown. The purpose of this study was to examine the possible mechanism of action of syncytin-1 in patients with anti-NMDAR encephalitis. Patients and Methods Twenty patients with anti-NMDAR encephalitis and eight controls were recruited. The protein levels of syncytin-1 in serum were determined using an enzyme-linked immunosorbent assay, and the transcript levels of syncytin-1 were determined using real-time quantitative PCR. Flow cytometry was used for peripheral blood lymphocyte subset detection. Further, the relationship between syncytin-1 levels and clinical features of anti-NMDAR encephalitis and peripheral blood lymphocyte subsets was analyzed. Results Compared with those in controls, higher syncytin-1 levels and percentage of B cells (CD3-CD19+) were observed in patients with anti-NMDAR encephalitis. Among anti-NMDAR encephalitis patients, the level of syncytin-1 positively correlated with the proportion of B cells and modified Rankin scale score at onset and after immunotherapy and negatively correlated with the proportion of CD3+ T cells. Conclusion An increased expression of Syncytin-1 is associated with the pathogenesis of anti-NMDAR encephalitis, providing evidence for elucidating the pathogenesis of the disease and suggesting novel therapeutic targets. Further, this study clarifies the role of syncytin-1 in neuroimmune disorders.

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“…As for AEs, treatment with bortezomib has been nearly exclusively reported in patients with anti-NMDAR encephalitis, in particular, in cases with severe disability who required a prolonged intensive care unit stay at the time of treatment administration, and in one patient with CASPR2 encephalitis, unsuccessfully treated with three cycles [38,39]. In the reported single cases or small case series, bortezomib was used after failure of conventional or unconventional treatments such as cyclophosphamide, rituximab, interleukin-2, or tocilizumab [39][40][41][42][43][44][45][46][47][48][49][50][51][52]. As expected, bortezomib has been shown to deplete antibody-secreting cells that were not susceptible to rituximab [52].…”

Section: Bortezomibmentioning

confidence: 99%

Treatment Options in Refractory Autoimmune Encephalitis

2022

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Autoimmune encephalitis represents a potentially treatable immune-mediated condition that is being more frequently recognized. Prompt immunotherapy is a key factor for the management of autoimmune encephalitis. First-line treatments include intravenous steroids, plasma exchange, and intravenous immunoglobulins, which can be combined in most severe cases. Rituximab and cyclophosphamide are administered as second-line agents in unresponsive cases. A minority of patients may still remain refractory, thus representing a major clinical challenge. In these cases, treatment strategies are controversial, and no guidelines exist. Treatments proposed for refractory autoimmune encephalitis include (1) cytokine-based drugs (such as tocilizumab, interleukin-2/basiliximab, anakinra, and tofacitinib); (2) plasma cell-depleting agents (such as bortezomib and daratumumab); and (3) treatments targeting intrathecal immune cells or their trafficking through the blood-brain barrier (such as intrathecal methotrexate and natalizumab). The efficacy evidence of these drugs is mostly based on case reports or small case series, with few reported controlled studies or systematic reviews. The aim of the present review is to summarize the current evidence and related methodological issues in the use of these drugs for the treatment of refractory autoimmune encephalitis.

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The short‐term efficacy of combined treatments targeting B cell and plasma cell in severe and refractory Anti‐N‐methyl‐D‐aspartate receptor encephalitis: Two case reports

Cited by 12 publications

References 10 publications

Characteristics and Prognosis of Autoimmune Encephalitis in the East of China: A Multi-Center Study

Characteristics and Prognosis of Autoimmune Encephalitis in the East of China: A Multi-Center Study

Role of Increased Syncytin-1 Expression in Pathogenesis of Anti-N-Methyl-d-Aspartate Receptor Encephalitis

Treatment Options in Refractory Autoimmune Encephalitis

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