Lauletta Antonio, Bosco Luca, Merlonghi Gioia, Falzone Yuri Matteo, Cheli Marta, Bencivenga Roberta Piera, Zoppi Dario, Ceccanti Marco, Kleefeld Felix, Léonard-Louis Sarah, Stenzel Werner, Benveniste Olivier, Maggi Lorenzo, Previtali Stefano Carlo, Garibaldi Matteo
Unit of Neuromuscular Diseases, Department of Neuroscience, Mental Health and Sensory Organs (NESMOS), Faculty of Medicine and Psychology, SAPIENZA University of Rome, Sant'Andrea Hospital, Via Di Grottarossa 1035-1039, 00189, Rome, Italy.
Institute of Experimental Neurology and Division of Neuroscience, Istituto Di Ricerca E Cura a Carattere Scientifico (IRCCS) Ospedale San Raffaele, Milan, Italy.
J Neurol. 2025 Jun 26;272(7):480. doi: 10.1007/s00415-025-13192-z.
Mitochondrial dysfunction is well documented in inclusion body myositis (IBM), but its role in non-IBM myositis remains unclear. This study aimed to investigate the prevalence and clinical significance of mitochondrial pathology in non-IBM myositis and to assess its potential role as a marker for disease progression towards IBM, treatment response, and clinical outcomes.
Muscle biopsies from 850 patients with inflammatory myopathy (IM) across 6 neuromuscular centers in Italy, France, and Germany were retrospectively analyzed. Inclusion required meeting diagnostic criteria for definite adult IM, mitochondrial pathology (age-exceeding numbers of COX-negative fibers), and exclusion of definite IBM according to Hilton-Jones 2013 criteria. The percentage of COX-negative fibers was quantified, correlated with clinical outcomes, and compared with myositis control cases without relevant signs of mitochondrial alterations.
Twenty-five patients with non-IBM myositis and mitochondrial abnormalities were identified. These patients, predominantly women (68%), had a mean onset age of 58.8 years. Polymyositis with mitochondrial pathology (PM-Mito) and nonspecific myositis (NSM) were the most prevalent subtypes (72%). The mean percentage of COX-negative fibers was 3% (0.25-8.5%) in these patients. The presence of mitochondrial pathology was associated with treatment refractoriness and worse clinical outcome evaluated based on residual muscle weakness and the level of independence (p < 0.005). A higher percentage of COX-negative fibers also correlated with poorer clinical outcomes (p = 0.031). Four patients, initially diagnosed with PM-Mito and NSM, progressed to definite IBM.
Mitochondrial dysfunction represents a key element informing about disease severity and poor clinical outcomes in non-IBM myositis. It may predict progression to IBM, especially in PM-Mito and NSM, and guide treatment strategies.
线粒体功能障碍在包涵体肌炎（IBM）中已有充分记录，但其在非IBM肌炎中的作用仍不清楚。本研究旨在调查非IBM肌炎中线粒体病理的患病率和临床意义，并评估其作为疾病进展为IBM、治疗反应和临床结局标志物的潜在作用。
对意大利、法国和德国6个神经肌肉中心的850例炎性肌病（IM）患者的肌肉活检进行回顾性分析。纳入标准为符合明确成人IM的诊断标准、线粒体病理（超过年龄预期数量的COX阴性纤维），并根据希尔顿-琼斯2013标准排除明确的IBM。对COX阴性纤维的百分比进行量化，与临床结局相关，并与无相关线粒体改变迹象的肌炎对照病例进行比较。
确定了25例非IBM肌炎合并线粒体异常的患者。这些患者以女性为主（68%），平均发病年龄为58.8岁。伴有线粒体病理的多发性肌炎（PM-Mito）和非特异性肌炎（NSM）是最常见的亚型（72%）。这些患者中COX阴性纤维的平均百分比为3%（0.25-8.5%）。线粒体病理的存在与治疗难治性以及基于残余肌肉无力和独立水平评估的较差临床结局相关（p<0.005）。较高百分比的COX阴性纤维也与较差的临床结局相关（p=0.031）。4例最初诊断为PM-Mito和NSM的患者进展为明确的IBM。
线粒体功能障碍是反映非IBM肌炎疾病严重程度和不良临床结局的关键因素。它可能预测进展为IBM,尤其是在PM-Mito和NSM中，并指导治疗策略。
