Interstitial lung disease (ILD) sometimes becomes a life-threatening complication of systemic autoimmune diseases; however, little is known about the immune response in lung lesions. We aimed to investigate humoural immunity in ILD associated with rheumatoid arthritis (RA), sjögren's syndrome (SjS), and mixed connective tissue disease (MCTD), using bronchoalveolar fluid (BALF) and serum samples from 15 patients with autoimmune disease associated-ILD. We first showed that BALF contained higher titers of disease-related autoantibodies than serum, suggesting the possibility of autoantibody production in lungs. Next, we produced 326 monoclonal antibodies from antibody-secreting cells in BALF, and the reactivity and their revertants, in which somatic hypermutations were reverted to germline, were analyzed. Among 123 antibodies from RA-ILD, 16 disease-related antibodies (anti-modified protein antibodies and rheumatoid factors) were identified, of which one antibody had both properties. The revertant antibodies changed their target modification in a complicated manner, suggesting that the antibodies were selected against various modifications in lungs. Among 146 antibodies from SjS-ILD and/or MCTD-ILD, seven anti-SSA/Ro60 antibodies and 15 anti-RNP antibodies were identified. Some of the anti-RNP antibodies recognized multiple RNP constituent proteins simultaneously, indicating that epitope spreading may progress in lungs. Our results revealed the existence of an active autoimmunity in the lungs of autoimmune disease associated-ILD.

间质性肺病 (ILD) 有时会成为系统性自身免疫性疾病的危及生命的并发症；然而，人们对肺部病变的免疫反应知之甚少。我们旨在使用支气管肺泡液 (BALF) 和 15 名自身免疫性疾病相关 ILD 患者的血清样本，研究与类风湿性关节炎 (RA)、干燥综合征 (SjS) 和混合结缔组织病 (MCTD) 相关的 ILD 的体液免疫。我们首先表明 BALF 含有比血清更高滴度的疾病相关自身抗体，这表明在肺部产生自身抗体的可能性。接下来，我们从 BALF 中的抗体分泌细胞产生了 326 种单克隆抗体，并分析了反应性及其回复体，其中体细胞超突变恢复为种系。在来自 RA-ILD 的 123 种抗体中，鉴定出16种疾病相关抗体（抗修饰蛋白抗体和类风湿因子），其中一种抗体具有两种特性。回复抗体以复杂的方式改变了它们的目标修饰，这表明这些抗体是针对肺中的各种修饰而选择的。在来自 SjS-ILD 和/或 MCTD-ILD 的 146 种抗体中，鉴定了 7 种抗 SSA/Ro60 抗体和 15 种抗 RNP 抗体。一些抗 RNP 抗体同时识别多个 RNP 组成蛋白，表明表位扩散可能在肺中进行。我们的研究结果揭示了自身免疫疾病相关 ILD 的肺部存在活跃的自身免疫。回复抗体以复杂的方式改变了它们的目标修饰，这表明这些抗体是针对肺中的各种修饰而选择的。在来自 SjS-ILD 和/或 MCTD-ILD 的 146 种抗体中，鉴定了 7 种抗 SSA/Ro60 抗体和 15 种抗 RNP 抗体。一些抗 RNP 抗体同时识别多个 RNP 组成蛋白，表明表位扩散可能在肺中进行。我们的研究结果揭示了自身免疫疾病相关 ILD 的肺部存在活跃的自身免疫。回复抗体以复杂的方式改变了它们的目标修饰，这表明这些抗体是针对肺中的各种修饰而选择的。在来自 SjS-ILD 和/或 MCTD-ILD 的 146 种抗体中，鉴定了 7 种抗 SSA/Ro60 抗体和 15 种抗 RNP 抗体。一些抗 RNP 抗体同时识别多个 RNP 组成蛋白，表明表位扩散可能在肺中进行。我们的研究结果揭示了自身免疫疾病相关 ILD 的肺部存在活跃的自身免疫。一些抗 RNP 抗体同时识别多个 RNP 组成蛋白，表明表位扩散可能在肺中进行。我们的研究结果揭示了自身免疫疾病相关 ILD 的肺部存在活跃的自身免疫。一些抗 RNP 抗体同时识别多个 RNP 组成蛋白，表明表位扩散可能在肺中进行。我们的研究结果揭示了自身免疫疾病相关 ILD 的肺部存在活跃的自身免疫。