PDF(Pubmed)
Abstract：
Interstitial lung disease is a common complication of anti-synthetase syndrome (ASS), and lymphocytic infiltration is often observed in the lesion. We have recently reported that disease-specific autoantibodies are produced by infiltrating lymphocytes in some autoimmune diseases. Here, we investigate the antigen specificity of B cells in the lung lesions of ASS patients. A total of 177 antibodies were produced from antibody-secreting cells in bronchoalveolar fluid (BALF) of three each of serum anti-Jo-1 and serum anti-EJ antibody-positive patients. Twelve to 30% and 50 to 62% of these antibodies were disease-specific autoantibodies, respectively. These autoantibodies recognized conformational epitopes of the whole self-antigen and had affinity maturations, indicating that self-antigens themselves are the target of humoral immunity. In addition, 100 antibodies were produced from two salivary gland tissues, obtained by chance, of ASS patients. Salivary glands are not generally recognized as lesions of ASS, but unexpectedly, ASS-related autoantibody production was also observed similar to that of BALF. Immunostaining confirmed the presence of ASS-related autoantibody-producing cells in salivary glands. Our results suggest that disease-specific autoantibody production at lesion sites is a common pathogenesis of autoimmune diseases, and that tissue-specific production of autoantibodies can provide insights regarding the distribution of organ manifestations in autoimmune diseases.
摘要：
间质性肺病是抗合成酶综合征（ASS）的常见并发症，并且经常在病变中观察到淋巴细胞浸润。我们最近报道，在某些自身免疫性疾病中，通过浸润淋巴细胞产生疾病特异性自身抗体。这里,我们研究了ASS患者肺部病变中B细胞的抗原特异性。从三种血清抗Jo-1和血清抗EJ抗体阳性患者的支气管肺泡液（BALF）中的抗体分泌细胞中总共产生了177种抗体。这些抗体中有12％至30％和50％至62％是疾病特异性自身抗体，分别。这些自身抗体识别整个自身抗原的构象表位，并具有亲和力成熟，表明自身抗原本身是体液免疫的目标。此外,从两个唾液腺组织中产生100种抗体，偶然获得的,ASS患者。唾液腺通常不被认为是ASS的病变，但出乎意料的是，还观察到与BALF相似的ASS相关的自身抗体产生。免疫染色证实唾液腺中存在ASS相关的自身抗体产生细胞。我们的结果表明，在病变部位产生疾病特异性自身抗体是自身免疫性疾病的常见发病机理，组织特异性自身抗体的产生可以提供有关自身免疫性疾病中器官表现分布的见解。
