Lindahl Hannes, Petersson Malin, Enoksson Sara Lind, Piehl Fredrik, Brauner Susanna
Department of Clinical Immunology and Transfusion Medicine, Karolinska University Hospital, Stockholm, Sweden.
Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
J Neurochem. 2025 Jun;169(6):e70126. doi: 10.1111/jnc.70126.
Myasthenia gravis (MG) is an autoimmune neurological disease characterized by potentially life-threatening muscular fatiguability. Symptoms are directly linked to autoantibodies targeting postsynaptic receptors of the neuromuscular junction. However, the underlying immunopathogenesis remains to be elucidated. This single-center study aimed to characterize peripheral blood lymphocytes in MG patients and to identify prognostic biomarkers. We retrospectively reanalyzed clinical flow cytometric data on blood B and T cells from 76 incident MG cases, comparing them to healthy individuals of relevant age range. Clinical data was collected from the Swedish MG registry and used for outcome analyses. Flow cytometry analyses were based on standardized panels established by the Human Immunology Project Consortium and included a 10-color T cell panel focused on memory, polarization, and activation states and an 8-color B cell panel that includes memory phenotypes, transitional B cells and plasmablasts. Groupwise comparisons, survival curves, and regression models adjusting for potential confounders were used to assess potential predictors of the primary outcome, minimal disease manifestation within one year. Untreated MG patients had higher frequencies of cluster of differentiation 4 (CD4) T cell frequencies compared to healthy individuals of approximately the same age (median 75% vs. 63% in age range 40-59 years and 65% in 60-81 years). High CD4 T cell frequencies (> 75% of total T cells) were associated with lower probability of minimal disease manifestation within one year (35% vs. 67%; log rank p = 0.032). In a multivariable Cox regression model assessing time to minimal disease manifestation, CD4 T cell frequency was an independent risk factor (p = 0.0014). In conclusion, MG patients appear to display an altered CD4 T cell phenotype and frequency of CD4 T cells is a potential prognostic biomarker.
重症肌无力（MG）是一种自身免疫性神经疾病，其特征为具有潜在生命威胁的肌肉易疲劳性。症状与针对神经肌肉接头突触后受体的自身抗体直接相关。然而，潜在的免疫发病机制仍有待阐明。这项单中心研究旨在描述MG患者外周血淋巴细胞的特征，并确定预后生物标志物。我们回顾性地重新分析了76例初发MG病例血液B细胞和T细胞的临床流式细胞术数据，并将其与相关年龄范围的健康个体进行比较。临床数据收集自瑞典MG登记处，并用于结果分析。流式细胞术分析基于人类免疫学项目联盟建立的标准化检测板，包括一个专注于记忆、极化和激活状态的10色T细胞检测板，以及一个包括记忆表型、过渡性B细胞和成浆细胞的8色B细胞检测板。采用组间比较、生存曲线和针对潜在混杂因素进行调整的回归模型，来评估主要结局（一年内最小疾病表现）的潜在预测因素。与年龄大致相同的健康个体相比，未经治疗的MG患者分化簇4（CD4）T细胞频率更高（40 - 59岁年龄组中位数为75%，健康个体为63%；60 - 81岁年龄组MG患者为65%）。高CD4 T细胞频率（>总T细胞的75%）与一年内最小疾病表现的较低概率相关（35%对67%；对数秩检验p = 0.032）。在评估达到最小疾病表现时间的多变量Cox回归模型中，CD4 T细胞频率是一个独立危险因素（p = 0.0014）。总之，MG患者似乎表现出CD4 T细胞表型改变，CD4 T细胞频率是一种潜在的预后生物标志物。
