Department of Dermatology, St. Marianna University School of Medicine, Kawasaki, Japan.
Division of Dermatology, Tohoku Medical and Pharmaceutical University, Sendai, Japan.
Pathobiology. 2022;89(1):23-28. doi: 10.1159/000519869. Epub 2021 Nov 23.
IgA vasculitis is a systemic disease that results from the entrapment of circulating IgA-containing immune complexes in small-vessel walls in the skin, kidneys, and gastrointestinal tract. An excessive formation of neutrophil extracellular traps (NETs) is involved in the pathogenesis of vasculitis, especially in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. This study aimed to clarify whether NETs are implicated in IgA vasculitis.
Twenty-two patients with IgA vasculitis and 4 healthy volunteers were enrolled in this study. Serum levels of myeloperoxidase (MPO)-DNA complex, a fragment derived from NETs, were determined by enzyme-linked immunosorbent assay (ELISA), and the association between MPO-DNA complex levels and clinical parameters was examined. The presence of the ANCA was also assessed by ELISA specific for MPO and proteinase 3 (PR3) and indirect immunofluorescence (IIF), followed by assessing the differences in clinical parameters with and without the ANCA.
Serum MPO-DNA complex levels were significantly higher in patients with IgA vasculitis than those in healthy controls. A significant positive correlation between the serum MPO-DNA complex and IgA levels was noted. Interestingly, 63.6% of IgA vasculitis patients were ANCA-positive in IIF with an atypical pattern, whereas neither MPO-ANCA nor PR3-ANCA was detected by ELISA. These findings indicated that some IgA vasculitis patients possessed the so called minor ANCA. Serum IgA and MPO-DNA complex levels and the frequency of hematuria in the minor ANCA-positive group were significantly higher than in the minor ANCA-negative group.
The collective findings suggested that NETs are certainly involved in the pathogenesis of IgA vasculitis.
IgA 血管炎是一种全身性疾病，其发病机制是循环 IgA 免疫复合物在皮肤、肾脏和胃肠道小血管壁中沉积。中性粒细胞胞外诱捕网（NETs）的过度形成与血管炎的发病机制有关，尤其是抗中性粒细胞胞质抗体（ANCA）相关性血管炎。本研究旨在阐明 NETs 是否与 IgA 血管炎有关。
本研究纳入了 22 例 IgA 血管炎患者和 4 名健康志愿者。采用酶联免疫吸附试验（ELISA）检测血清髓过氧化物酶（MPO）-DNA 复合物（一种源自 NETs 的片段）的水平，并探讨 MPO-DNA 复合物水平与临床参数之间的关系。还通过 ELISA 特异性检测 MPO 和蛋白酶 3（PR3）以及间接免疫荧光（IIF）检测抗中性粒细胞胞质抗体（ANCA），评估 ANCA 的存在情况，并比较有无 ANCA 时的临床参数差异。
IgA 血管炎患者的血清 MPO-DNA 复合物水平明显高于健康对照组。血清 MPO-DNA 复合物与 IgA 水平呈显著正相关。有趣的是，63.6%的 IgA 血管炎患者在 IIF 中表现为不典型模式的 ANCA 阳性，而 ELISA 检测不到 MPO-ANCA 或 PR3-ANCA。这些发现表明，一些 IgA 血管炎患者存在所谓的小 ANCA。小 ANCA 阳性组的血清 IgA 和 MPO-DNA 复合物水平以及血尿频率均明显高于小 ANCA 阴性组。
这些结果表明 NETs 确实参与了 IgA 血管炎的发病机制。
