皮肌炎患者肺部免疫复合物形成增强。
Enhanced immune complex formation in the lungs of patients with dermatomyositis.
机构信息
Division of Respirology, Neurology, and Rheumatology, Department of Medicine, Kurume University School of Medicine, 67 Asahi-Machi, Kurume, Fukuoka, 830-0011, Japan.
Department of Pathology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.
出版信息
Respir Res. 2023 Mar 19;24(1):86. doi: 10.1186/s12931-023-02362-0.
BACKGROUND
Interstitial lung disease is frequently comorbid with dermatomyositis and has a poor prognosis, especially in patients with the anti-melanoma differentiation-associated gene 5 (MDA5) autoantibody. However, the pathogenesis of dermatomyositis-related interstitial lung disease remains unclear.
METHODS
We examined 18 and 19 patients with dermatomyositis-related interstitial lung disease and idiopathic pulmonary fibrosis (control), respectively. Lung tissues obtained from these patients were semi-quantitatively evaluated by immunohistochemical staining with in-house anti-human MDA5 monoclonal antibodies, as well as anti-human immunoglobulin (Ig) G, IgM, IgA, and complement component 3(C3) antibodies. We established human MDA5 transgenic mice and treated them with rabbit anti-human MDA5 polyclonal antibodies, and evaluated lung injury and Ig and C3 expression.
RESULTS
MDA5 was moderately or strongly expressed in the lungs of patients in both groups, with no significant differences between the groups. However, patients with dermatomyositis-related interstitial lung disease showed significantly stronger expression of C3 (p < 0.001), IgG (p < 0.001), and IgM (p = 0.001) in the lungs than control. Moreover, lung C3, but IgG, IgA, nor IgM expression was significantly stronger in MDA5 autoantibody-positive dermatomyositis-related interstitial lung disease (n = 9) than in MDA5 autoantibody-negative dermatomyositis-related interstitial lung disease (n = 9; p = 0.022). Treatment with anti-MDA5 antibodies induced lung injury in MDA5 transgenic mice, and strong immunoglobulin and C3 expression was observed in the lungs of the mice.
CONCLUSION
Strong immunoglobulin and C3 expression in the lungs involve lung injury related to dermatomyositis-related interstitial lung disease. Enhanced immune complex formation in the lungs may contribute to the poor prognosis of MDA5 autoantibody-positive dermatomyositis-related interstitial lung disease.
背景
间质性肺病常与皮肌炎并存，且预后不良，尤其是抗黑色素瘤分化相关基因 5（MDA5）自身抗体阳性患者。然而，皮肌炎相关间质性肺病的发病机制仍不清楚。
方法
我们分别检测了 18 例皮肌炎相关间质性肺病患者和 19 例特发性肺纤维化（对照组）患者的肺组织。使用内部抗人 MDA5 单克隆抗体以及抗人免疫球蛋白（Ig）G、IgM、IgA 和补体成分 3（C3）抗体，对肺组织进行半定量免疫组化染色。我们建立了人 MDA5 转基因小鼠，并使用兔抗人 MDA5 多克隆抗体进行处理，评估肺损伤和 Ig 及 C3 的表达。
结果
两组患者的肺组织中 MDA5 均呈中度或强表达，两组间无显著差异。然而，皮肌炎相关间质性肺病患者的肺组织中 C3（p<0.001）、IgG（p<0.001）和 IgM（p=0.001）表达显著增强。此外，在 MDA5 自身抗体阳性皮肌炎相关间质性肺病（n=9）患者的肺中，C3 （但 IgG、IgA 和 IgM 表达均无差异；p=0.022）表达明显强于 MDA5 自身抗体阴性皮肌炎相关间质性肺病患者的肺中。抗 MDA5 抗体治疗诱导 MDA5 转基因小鼠肺损伤，且观察到小鼠肺中存在强烈的免疫球蛋白和 C3 表达。
结论
肺中强烈的免疫球蛋白和 C3 表达与皮肌炎相关间质性肺病引起的肺损伤有关。肺中免疫复合物的形成增强可能导致 MDA5 自身抗体阳性皮肌炎相关间质性肺病的预后不良。
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