Dermatomyositis: Muscle Pathology According to Antibody Subtypes.
Dermatomyositis: Muscle Pathology According to Antibody Subtypes.
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DOI：
10.1212/wnl.0000000000013176
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发表时间：
2022-02-15
期刊：
影响因子：
9.9
通讯作者：
Nishino I
中科院分区：
文献类型：
--
作者：
Tanboon J;Inoue M;Saito Y;Tachimori H;Hayashi S;Noguchi S;Okiyama N;Fujimoto M;Nishino I
皮肌炎特异性抗体（DMSA）在皮肌炎患者中的发现提高了人们对抗体亚型之间各种肌病特征的认识。然而，只有束周萎缩和束周粘病毒耐药蛋白A（MxA）的过度表达被正式纳入皮肌炎分类的明确病理标准。我们的目的是证明MxA阳性皮肌炎的肌肉病理学特征，以确定不同DMSA亚型的特征性肌肉病理学特征。我们对2009年1月至2020年12月期间在三级肌肉疾病实验室诊断的皮肌炎患者的肌肉活检进行了回顾性病理学审查。我们纳入了所有肌浆MxA表达和DMSA血清阳性的肌肉活检。所有DMSA检测阴性的MxA阳性肌肉活检被纳入血清阴性皮肌炎。我们通过组织化学、酶组织化学和免疫组织化学研究（通常用于诊断炎症性肌病）评估了根据4个病理领域（肌纤维、炎症、血管和结缔组织）分层的组织学特征和感兴趣的组织学特征。我们进行了超微结构研究的54个标本。共纳入256例患者。其中，249例患者对5种DMSA中的1种呈阳性（血清阳性患者：87抗转录中介因子1-γ [TIF 1-γ]，40抗复合核小体重塑组蛋白脱乙酰酶[Mi-2]，29抗黑色素瘤分化基因5 [MDA 5]，83抗核基质蛋白2 [NXP-2]，和10名抗小泛素样修饰物激活酶[SAE]皮肌炎）和7名患者对所有5种DMSA均为阴性（血清阴性患者）。每种DMSA亚型的典型肌病理学特征如下：抗TIF 1-γ抗体伴空泡化/穿孔纤维（64.7%; p < 0.001）和HLA-ABC染色的束周强化（75.9%; p < 0.001）;抗Mi-2具有明显的肌纤维损伤（评分4.9 ± 2.1; p < 0.001），炎性细胞浸润（评分8.0 ± 3.0; p = 0.002），束周萎缩（67.5%; p = 0.02），束周坏死（52.5%; P < 0.001），增加肌周碱性磷酸酶活性（70.0%; p < 0.001），中央坏死外周再生纤维（45.0%; p = 0.002），肌膜攻击复合物沉积（67.5%; p < 0.001）;抗MDA 5，MxA呈散在/弥漫染色模式（65.5%; p < 0.001），肌肉病理和炎症特征较少;抗NXP-2抗体伴微梗死（26.5%; p < 0.001）;抗SAE和血清阴性皮肌炎伴HLA-DR表达（分别为50.0%; p = 0.02和57.1%; p = 0.02）。我们描述了一个全面的皮肌炎的血清学-病理学相关性，主要使用MxA表达作为纳入标准。在我们的研究中，DMSA与不同的肌肉病理学特征相关，表明每个亚型的潜在病理生物学机制不同。
Discoveries of dermatomyositis-specific antibodies (DMSAs) in patients with dermatomyositis raised awareness of various myopathologic features among antibody subtypes. However, only perifascicular atrophy and perifascicular myxovirus resistant protein A (MxA) overexpression were officially included as definitive pathologic criteria for dermatomyositis classification. We aimed to demonstrate myopathologic features in MxA-positive dermatomyositis to determine characteristic myopathologic features in different DMSA subtypes. We performed a retrospective pathology review of muscle biopsies of patients with dermatomyositis diagnosed between January 2009 and December 2020 in a tertiary laboratory for muscle diseases. We included all muscle biopsies with sarcoplasmic expression for MxA and seropositivity for DMSAs. MxA-positive muscle biopsies that tested negative for all DMSAs were included as seronegative dermatomyositis. We evaluated histologic features stratified according to 4 pathology domains (muscle fiber, inflammatory, vascular, and connective tissue) and histologic features of interest by histochemistry, enzyme histochemistry, and immunohistochemical study commonly used in the diagnosis of inflammatory myopathy. We performed ultrastructural studies of 54 available specimens. A total of 256 patients were included. Of these, 249 patients were positive for 1 of the 5 DMSAs (seropositive patients: 87 anti–transcription intermediary factor 1-γ [TIF1-γ], 40 anti–complex nucleosome remodeling histone deacetylase [Mi-2], 29 anti–melanoma differentiation gene 5 [MDA5], 83 anti–nuclear matrix protein 2 [NXP-2], and 10 anti–small ubiquitin-like modifier-activating enzyme [SAE] dermatomyositis) and 7 patients were negative for all 5 DMSAs (seronegative patients). Characteristic myopathologic features in each DMSA subtype were as follows: anti-TIF1-γ with vacuolated/punched out fibers (64.7%; p < 0.001) and perifascicular enhancement in HLA-ABC stain (75.9%; p < 0.001); anti-Mi-2 with prominent muscle fiber damage (score 4.9 ± 2.1; p < 0.001), inflammatory cell infiltration (score 8.0 ± 3.0; p = 0.002), perifascicular atrophy (67.5%; p = 0.02), perifascicular necrosis (52.5%; p < 0.001), increased perimysial alkaline phosphatase activity (70.0%; p < 0.001), central necrotic peripheral regenerating fibers (45.0%; p = 0.002), and sarcolemmal membrane attack complex deposition (67.5%; p < 0.001); anti-MDA5 with scattered/diffuse staining pattern of MxA (65.5%; p < 0.001) with less muscle pathology and inflammatory features; anti-NXP-2 with microinfarction (26.5%; p < 0.001); and anti-SAE and seronegative dermatomyositis with HLA-DR expression (50.0%; p = 0.02 and 57.1%; p = 0.02, respectively). We describe a comprehensive serologic–pathologic correlation of dermatomyositis primarily using MxA expression as an inclusion criterion. In our study, DMSAs were associated with distinctive myopathologic features suggesting different underlying pathobiologic mechanisms in each subtype.