Pathophysiology of ANCA-associated small vessel vasculitis.
Pathophysiology of ANCA-associated small vessel vasculitis.
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DOI：
10.1007/s11926-010-0138-6
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发表时间：
2010-12
影响因子：
5
通讯作者：
Kallenberg, Cees G M
中科院分区：
文献类型：
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作者：
Kallenberg, Cees G M
针对蛋白酶3（PR 3-ANCA）或髓过氧化物酶（MPO-ANCA）的抗神经细胞胞质自身抗体（ANCA）与ANCA相关性血管炎-韦格纳肉芽肿病、显微镜下多血管炎和Churg-Strauss综合征密切相关。临床观察，包括利妥昔单抗治疗的B细胞耗竭的疗效，支持但不能证明ANCA在ANCA相关性血管炎中的致病作用。体外实验研究表明，ANCA、中性粒细胞、补体系统旁路途径和内皮细胞的相互作用可导致内皮细胞溶解。MPO-ANCA的致病作用得到了小鼠和大鼠体内实验研究的有力支持，这些研究还阐明了病变发展中涉及的致病机制。不幸的是，PR 3-ANCA相关的韦格纳肉芽肿病的动物模型还不可用。在这里，细胞免疫似乎也发挥了重要作用，特别是通过产生白细胞介素-17的T细胞，与病变中的肉芽肿性炎症一致。最后，微生物因素，特别是金黄色葡萄球菌和革兰氏阴性菌，似乎参与疾病的诱导和表达，但需要进一步的研究来确定它们在疾病发展中的确切作用。
Antineutrophil cytoplasmic autoantibodies (ANCAs) directed to proteinase 3 (PR3-ANCA) or myeloperoxidase (MPO-ANCA) are strongly associated with the ANCA-associated vasculitides—Wegener’s granulomatosis, microscopic polyangiitis, and Churg-Strauss syndrome. Clinical observations, including the efficacy of B-cell depletion via rituximab treatment, support—but do not prove—a pathogenic role for ANCA in the ANCA-associated vasculitides. In vitro experimental studies show that the interplay of ANCA, neutrophils, the alternative pathway of the complement system, and endothelial cells could result in lysis of the endothelium. A pathogenic role for MPO-ANCA is strongly supported by in vivo experimental studies in mice and rats, which also elucidate the pathogenic mechanisms involved in lesion development. Unfortunately, an animal model for PR3-ANCA–associated Wegener’s granulomatosis is not yet available. Here, cellular immunity appears to play a major role as well, particularly via interleukin-17–producing T cells, in line with granulomatous inflammation in the lesions. Finally, microbial factors, in particular Staphylococcus aureus and gram-negative bacteria, seem to be involved in disease induction and expression, but further studies are needed to define their precise role in disease development.