Kaneko Toshiyuki, Amano Hirofumi, Kawano Shinya, Minowa Kentaro, Ando Seiichiro, Watanabe Takashi, Nakano Soichiro, Suzuki Jun, Morimoto Shinji, Tokano Yoshiaki, Takasaki Yoshinari
Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine , Tokyo , Japan.
Mod Rheumatol. 2014 Mar;24(2):310-5. doi: 10.3109/14397595.2013.843748. Epub 2013 Nov 7.
B cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) are known to be crucial for B cell maturation and survival, and increased expression of these factors in various autoimmune diseases has been reported. Human B cells produce two IgA subclasses: IgA1 and IgA2, the latter being abundant in the distal intestine, saliva, colostrum and bronchial fluid. We investigated these parameters in patients with mixed connective tissue disease (MCTD) complicated by interstitial lung disease (ILD+), and compared them with those in MCTD patients without ILD (ILD-). Sixty-three MCTD patients were divided into two groups: 21 ILD+ patients and 42 ILD- patients. In each patient group we analyzed soluble BAFF/APRIL using ELISA, and IgA1 and IgA2 using double immunodiffusion. Furthermore, we analyzed BAFF-APRIL receptors, BCMA, BAFF-R and TACI, using flow cytometry. The ILD+ patients had significantly higher levels of BAFF/APRIL than the ILD- patients. There were significant correlations between BAFF/APRIL, BAFF/KL-6 and APRIL/KL-6. Although there was no significant inter-group difference in the serum IgA1 level, ILD+ patients had a significantly elevated IgA2 level in comparison with ILD- patients. Moreover, although there were no significant inter-group differences in the expression of BCMA, BAFF-R and TACI on B cells, the expression of BAFF-R was significantly decreased in the ILD+ patients. In recent years, relationships between BAFF/APRIL and IgA subclass have been reported. Our results suggest that an elevated level of BAFF/APRIL drives the maturation of B cells, subsequently leading to IgA2 class switching, and possibly to the development of ILD in patients with MCTD.
已知B细胞活化因子（BAFF）和增殖诱导配体（APRIL）对B细胞的成熟和存活至关重要，并且已有报道称这些因子在各种自身免疫性疾病中表达增加。人类B细胞产生两种IgA亚类：IgA1和IgA2，后者在远端肠道、唾液、初乳和支气管液中含量丰富。我们研究了合并间质性肺病（ILD+）的混合性结缔组织病（MCTD）患者的这些参数，并将其与无ILD的MCTD患者（ILD-）的参数进行比较。63例MCTD患者分为两组：21例ILD+患者和42例ILD-患者。在每个患者组中，我们使用ELISA分析可溶性BAFF/APRIL，并使用双向免疫扩散法分析IgA1和IgA2。此外，我们使用流式细胞术分析BAFF-APRIL受体、BCMA、BAFF-R和TACI。ILD+患者的BAFF/APRIL水平显著高于ILD-患者。BAFF/APRIL、BAFF/KL-6和APRIL/KL-6之间存在显著相关性。虽然血清IgA1水平在组间无显著差异，但与ILD-患者相比，ILD+患者的IgA2水平显著升高。此外，虽然B细胞上BCMA、BAFF-R和TACI的表达在组间无显著差异，但ILD+患者中BAFF-R的表达显著降低。近年来，已有关于BAFF/APRIL与IgA亚类之间关系的报道。我们的结果表明，BAFF/APRIL水平升高会驱动B细胞成熟，随后导致IgA2类别转换，并可能导致MCTD患者发生ILD。
