Differential clinicopathologic features of EGPA-associated neuropathy with and without ANCA
Differential clinicopathologic features of EGPA-associated neuropathy with and without ANCA
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DOI：
10.1212/wnl.0000000000009309
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发表时间：
2020-04-21
期刊：
影响因子：
9.9
通讯作者：
Sobue, Gen
中科院分区：
文献类型：
--
作者：
Nishi, Ryoji;Koike, Haruki;Sobue, Gen
目的探讨嗜酸性肉芽肿病合并多血管炎（EGPA）相关神经病变的临床病理特征，重点探讨抗中性粒细胞胞浆抗体（ANCAs）的存在或不存在。方法对82例egpa相关性神经病变患者的腓肠神经活检标本进行临床和病理检查。在这些患者中，32.9%的人髓过氧化物酶(MPO)-ANCA阳性，67.1%的人MPO-ANCA阴性。78例患者PR3-ANCA均为阴性。结果mpo - anca阳性组上肢症状作为首发神经病表现的频率高于mpo - anca阴性组（44.4% vs 14.6%, p < 0.01）。mpo - anca阳性组血清c反应蛋白水平显著高于mpo - anca阴性组（p < 0.05）。腓肠神经活检标本显示神经外血管提示血管炎（即血管结构破坏）；这些结果在mpo - anca阳性组比mpo - anca阴性组更常见（p < 0.0001）。相反，mpo - anca阴性组神经外血管腔内嗜酸性粒细胞数量（p < 0.01）和腔内嗜酸性粒细胞闭塞的神经外血管数量（p < 0.05）均高于mpo - anca阳性组。mpo - anca阴性组神经内膜嗜酸性粒细胞浸润率高于mpo - anca阳性组（p < 0.01）。结论本研究提示EGPA的发病机制至少包括两种不同的机制：anca相关血管炎导致缺血效应和炎症，这在mpo - anca阳性患者中突出；嗜酸性粒细胞相关血管闭塞导致缺血和嗜酸性粒细胞相关组织损伤，这在mpo - anca阴性患者中突出。
Objective To investigate the clinicopathologic features of eosinophilic granulomatosis with polyangiitis (EGPA)-associated neuropathy with a focus on the presence or absence of anti-neutrophil cytoplasmic antibodies (ANCAs). Methods We examined the clinical features and pathologic findings of sural nerve biopsy specimens from 82 patients with EGPA-associated neuropathy. Of these patients, 32.9% were myeloperoxidase (MPO)-ANCA positive, and 67.1% were MPO-ANCA negative. PR3-ANCA was negative in all of 78 examined patients. Results Upper limb symptoms were more frequently reported as initial neuropathic manifestations in the MPO-ANCA-positive group than in the MPO-ANCA-negative group (44.4% vs 14.6%, p < 0.01). The serum levels of C-reactive protein were significantly higher in the MPO-ANCA-positive group than in the MPO-ANCA-negative group (p < 0.05). Sural nerve biopsy specimens showed findings suggestive of vasculitis (i.e., destruction of vascular structures) in epineurial vessels; these results were seen more frequently in the MPO-ANCA-positive group than in the MPO-ANCA-negative group (p < 0.0001). Conversely, the numbers of eosinophils in the lumen of the epineurial vessels (p < 0.01) and epineurial vessels occluded by intraluminal eosinophils (p < 0.05) were higher in the MPO-ANCA-negative group than in the MPO-ANCA-positive group. Furthermore, the incidence of eosinophil infiltration in the endoneurium was higher in the MPO-ANCA-negative group than in the MPO-ANCA-positive group (p < 0.01). Conclusions This study suggests that the pathogenesis of EGPA comprises at least 2 distinct mechanisms: ANCA-associated vasculitis resulting in ischemic effects and inflammation, which is prominent in MPO-ANCA-positive patients, and eosinophil-associated vascular occlusion leading to ischemia and eosinophil-associated tissue damage, which is conspicuous in MPO-ANCA-negative patients.