Mayer Tobias, Scholle Leila, Foerster Laura, Schneider Ilka, Stoltenburg-Didinger Gisela, Delank Karl-Stefan, Kendzierski Thomas, Koelsch Anna, Kleeberg Kathleen, Kraya Torsten, Barba Lorenzo, Naegel Steffen, Schänzer Anne, Otto Markus, Mensch Alexander
Department of Neurology, University Medicine Halle, Halle (Saale), Germany.
Department of Neurology, St. Georg Hospital Leipzig, Leipzig, Germany.
Neuropathol Appl Neurobiol. 2025 Jun;51(3):e70019. doi: 10.1111/nan.70019.
Diagnosis of inclusion body myositis (IBM) is difficult and currently based on a combination of clinical and (immuno)histological findings. Biomarkers facilitating the diagnostic process are needed. Alpha-synuclein (αSN) aggregates are a known histological feature of IBM, but there is a lack of information on their diagnostic relevance. Furthermore, serum αSN concentrations in IBM have not been investigated.
Immunohistochemical staining for αSN was performed on 63 biopsies (19 IBM, 21 other inflammatory myopathies, 20 other myopathies and 3 healthy controls), and αSN reactive fibres were quantified. The serum concentration of αSN was determined by ELISA in 156 serum samples (11 IBM, 25 other inflammatory myopathies, 53 hereditary myopathies, 30 mitochondriopathies and 37 healthy controls).
The proportion of fibres with αSN immunoreactivity was significantly higher in IBM compared to all groups (p < 0.001) and discriminated IBM against all other neuromuscular disorders with a sensitivity of 79% and a specificity of 85%, which further improved when only non-regenerating fibres were examined. In serum, αSN concentrations in IBM were generally not different from healthy controls. However, serum concentrations were inversely correlated with disease duration (r = -0.62, p = 0.04) and positively correlated with the IBM functional rating scale (r = 0.74, p = 0.01). Consequently, stratification according to these clinical parameters showed significantly lower serum αSN concentrations in late-stage, more severely affected patients.
αSN reactivity may serve as an additional immunohistochemical marker for IBM diagnosis. Furthermore, this study indicates that αSN serum concentrations decrease with disease duration and clinical deterioration. Therefore, serum αSN may be provisionally considered a monitoring biomarker in IBM, pending further studies.
包涵体肌炎（IBM）的诊断较为困难，目前基于临床和（免疫）组织学检查结果的综合判断。需要有助于诊断过程的生物标志物。α-突触核蛋白（αSN）聚集体是IBM已知的组织学特征，但缺乏关于其诊断相关性的信息。此外，尚未对IBM患者血清αSN浓度进行研究。
对63例活检组织（19例IBM、21例其他炎症性肌病、20例其他肌病和3例健康对照）进行αSN免疫组化染色，并对αSN反应性纤维进行定量分析。采用酶联免疫吸附测定法（ELISA）检测156份血清样本（11例IBM、25例其他炎症性肌病、53例遗传性肌病、30例线粒体肌病和37例健康对照）中αSN的血清浓度。
与所有组相比，IBM中具有αSN免疫反应性的纤维比例显著更高（p < 0.001），以79%的敏感性和85%的特异性将IBM与所有其他神经肌肉疾病区分开来，仅检查非再生纤维时，诊断效能进一步提高。在血清中，IBM患者的αSN浓度总体上与健康对照无差异。然而，血清浓度与病程呈负相关（r = -0.62，p = 0.04），与IBM功能评定量表呈正相关（r = 0.74，p = 0.01）。因此，根据这些临床参数进行分层分析显示，晚期、病情更严重的患者血清αSN浓度显著降低。
αSN反应性可作为IBM诊断的一种额外免疫组化标志物。此外，本研究表明αSN血清浓度随病程延长和临床病情恶化而降低。因此，在进一步研究之前，血清αSN可暂被视为IBM的一种监测生物标志物。
