34PCharacterization of inflammatory infiltrate in inclusion body myositis and its comparison with other IIMs

IF 2.8 4区医学 Q2 CLINICAL NEUROLOGY

Neuromuscular Disorders Pub Date : 2025-09-01 DOI:10.1016/j.nmd.2025.105497

N. Rajput

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引用次数: 0

Abstract

Inclusion body myositis (IBM) is an inflammatory autoimmune disorder of skeletal muscle affecting patients over the age of 40, with distinctive clinical and histopathological features. A direct cause of

IBM muscle damage is T cell–mediated cytotoxicity of IBM myofibers. On muscle biopsy, IBM is characterized by a peculiar combination of endomysial inflammation, rimmed vacuoles, and protein aggregation. This ambispective observational study included 26 patients biopsy proven IIMs cases over a period of six years. Both retrospective and prospective data were collected, including detailed clinical profiles, laboratory parameters, and histopathological features. To further characterize the nature of the inflammatory infiltrate, confocal microscopy was performed using a panel of nine inflammatory cell markers: CD3, CD4, CD8, CD16, CD56, CD68, CD86, CD163 and KLRG1. These markers were analyzed in dual combinations. Twenty-six biopsy proven patients of IIMs (16 IBM + 8 DM + 1OM + 1IMNM) were included in this study. The baseline demographics included age 36-72 years, (Male:Female;16:10). Clinically differential diagnosis included inflammatory and metabolic myopathies, LGMD, SLE with myopathy. Histopathological features in inclusion body myositis included loss of fascicular architecture (12/16 cases), rimmed vacuoles (8/16 cases), variation in fibre size (all 16 cases) and inflammatory infiltrate in all 16 cases with CD3 and CD8 positivity in 14/16 cases, and two cases with CD3 and CD4 positivity. Dermatomyositis features included loss of fascicular architecture (6/8 cases), Perifascicular atrophy (5/8 cases), variation in fiber size (8/8 cases), chronic inflammatory infiltrate (6/8 cases; with CD3 and CD8 positive cells in 4/8 cases, CD3, CD4 and CD8 positive cells in 2/8 cases). Single case of IMNM showed maintained fascicular architecture with mild variation in size, along with few degenerating fibers. On confocal microscopy 6/16 IBM cases showed inflammatory cells with dual positivity for CD3 and CD8, 5/16 IBM cases showed KLRG1 positive cells out of which single case showed dual positivity for CD8 and KLRG1, 3/16 IBM cases showed CD68 positive cells while all IBM cases were negative for CD16, CD56, CD86, and CD163 inflammatory markers. On confocal 3/8 dermatomyositis cases showed dual positivity for CD3 and CD8 markers, and single cases showed cells positive for CD16, CD68, and KLRG1, respectively. While all dermatomyositis cases were negative for CD86, CD163, and CD56 inflammatory markers. The IMNM case exhibited a complete absence of inflammatory cells. In comparison, the overlap myositis case showed selective infiltration by CD3-positive cells, with all remaining markers remained negative. In our analysis, inclusion body myositis showed prominent infiltration by CD8+ and KLRG1+ highly differentiated T cells, a pattern not observed in dermatomyositis or other IIMs. Given the limited response to steroid treatment in IBM, these cell populations could serve as potential targets for alternative therapies.

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34p包涵体肌炎的炎症浸润特征及其与其他IIMs的比较

包涵体肌炎（IBM）是一种影响40岁以上患者的骨骼肌炎症性自身免疫性疾病，具有独特的临床和组织病理学特征。IBM肌肉损伤的直接原因是T细胞介导的IBM肌纤维细胞毒性。在肌肉活检中，IBM的特征是肌内膜炎症、边缘空泡和蛋白质聚集的特殊组合。这项双视角观察性研究包括26例活检证实的IIMs病例，为期6年。收集回顾性和前瞻性资料，包括详细的临床资料、实验室参数和组织病理学特征。为了进一步表征炎症浸润的性质，使用共聚焦显微镜观察9种炎症细胞标志物：CD3、CD4、CD8、CD16、CD56、CD68、CD86、CD163和KLRG1。对这些标记进行双组合分析。本研究纳入26例活检证实的IIMs患者（16例IBM + 8例DM + 1OM + 1IMNM）。基线人口统计包括年龄36-72岁，（男女比例16:10）。临床鉴别诊断包括炎性和代谢性肌病、LGMD、SLE合并肌病。包涵体肌炎的组织病理学特征包括束状结构丧失（12/16例）、边缘空泡（8/16例）、纤维大小改变（全部16例）和炎症浸润（全部16例），CD3和CD8阳性（14/16例），CD3和CD4阳性2例。皮肌炎的特征包括肌束结构丧失（6/8例）、肌束周围萎缩（5/8例）、纤维大小改变（8/8例）、慢性炎症浸润（6/8例；CD3、CD8阳性细胞4/8例，CD3、CD4、CD8阳性细胞2/8例）。单例IMNM显示维持的束状结构，大小轻微变化，伴少量变性纤维。共聚焦显微镜下，6/16例IBM病例显示CD3和CD8双阳性，5/16例IBM病例显示KLRG1阳性，其中1例显示CD8和KLRG1双阳性，3/16例IBM病例显示CD68阳性，而所有IBM病例均为CD16、CD56、CD86和CD163炎症标志物阴性。共聚焦3/8皮肌炎患者CD3和CD8标记物双阳性，单发病例CD16、CD68和KLRG1细胞分别阳性。而所有皮肌炎病例的CD86、CD163和CD56炎症标志物均为阴性。IMNM病例显示炎症细胞完全缺失。相比之下，重叠性肌炎病例显示cd3阳性细胞选择性浸润，其余所有标志物均为阴性。在我们的分析中，包涵体肌炎表现出CD8+和KLRG1+高分化T细胞的显著浸润，这一模式在皮肌炎或其他IIMs中未观察到。鉴于IBM对类固醇治疗的反应有限，这些细胞群可以作为替代疗法的潜在靶点。

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来源期刊

Neuromuscular Disorders 医学-临床神经学

CiteScore

4.60

自引率

3.60%

发文量

543

审稿时长

53 days

期刊介绍： This international, multidisciplinary journal covers all aspects of neuromuscular disorders in childhood and adult life (including the muscular dystrophies, spinal muscular atrophies, hereditary neuropathies, congenital myopathies, myasthenias, myotonic syndromes, metabolic myopathies and inflammatory myopathies). The Editors welcome original articles from all areas of the field: • Clinical aspects, such as new clinical entities, case studies of interest, treatment, management and rehabilitation (including biomechanics, orthotic design and surgery). • Basic scientific studies of relevance to the clinical syndromes, including advances in the fields of molecular biology and genetics. • Studies of animal models relevant to the human diseases. The journal is aimed at a wide range of clinicians, pathologists, associated paramedical professionals and clinical and basic scientists with an interest in the study of neuromuscular disorders.