Murata Y, Aoe K, Mimura-Kimura Y, Murakami T, Oishi K, Matsumoto T, Ueoka H, Matsunaga K, Yano M, Mimura Y
The Department of Clinical Research, National Hospital Organization Yamaguchi-Ube Medical Center, Ube, Japan.
The Department of Respiratory Medicine, National Hospital Organization Yamaguchi-Ube Medical Center, Ube, Japan.
Clin Exp Immunol. 2017 Oct;190(1):133-142. doi: 10.1111/cei.12999. Epub 2017 Jul 17.
The cause of pleural effusion remains uncertain in approximately 15% of patients despite exhaustive evaluation. As recently described immunoglobulin (Ig)G4-related disease is a fibroinflammatory disorder that can affect various organs, including the lungs, we investigate whether idiopathic pleural effusion includes IgG4-associated etiology. Between 2000 and 2012, we collected 830 pleural fluid samples and reviewed 35 patients with pleural effusions undiagnosed after pleural biopsy at Yamaguchi-Ube Medical Center. Importantly, IgG4 immunostaining revealed infiltration of IgG4-positive plasma cells in the pleura of 12 patients (34%, IgG4 group). The median effusion IgG4 level was 41 mg/dl in the IgG4 group and 27 mg/dl in the IgG4 group (P < 0·01). The light and heavy chains of effusion IgG4 antibodies of patients in the IgG4 group were heterogeneous by two-dimensional electrophoresis, indicating the absence of clonality of the IgG4 antibodies. Interestingly, the κ light chains were more heterogeneous than the λ light chains. The measurement of the κ and λ free light chain (FLC) levels in the pleural fluids showed significantly different κ FLC levels (median: 28·0 versus 9·1 mg/dl, P < 0·01) and κ/λ ratios (median: 2·0 versus 1·2, P < 0·001) between the IgG4 and IgG4 groups. Furthermore, the κ/λ ratios were correlated with the IgG4 /IgG plasma cell ratios in the pleura of the IgG4 group. Taken together, these results demonstrate the involvement of IgG4 in certain idiopathic pleural effusions and provide insights into the diagnosis, pathogenesis and therapeutic opportunities of IgG4-associated pleural effusion.
尽管进行了详尽的评估，但仍有大约15%的患者胸腔积液的病因尚不明确。正如最近所描述的，免疫球蛋白（Ig）G4相关疾病是一种可影响包括肺在内的各种器官的纤维炎症性疾病，我们研究特发性胸腔积液是否包括IgG4相关病因。在2000年至2012年期间，我们收集了830份胸腔积液样本，并回顾了山口宇部医疗中心35例胸腔活检后仍未确诊的胸腔积液患者。重要的是，IgG4免疫染色显示12例患者（34%，IgG4组）的胸膜中有IgG4阳性浆细胞浸润。IgG4组胸腔积液IgG4水平中位数为41mg/dl，非IgG4组为27mg/dl（P<0.01）。IgG4组患者胸腔积液IgG4抗体的轻链和重链经二维电泳显示为异质性，表明IgG4抗体无克隆性。有趣的是，κ轻链比λ轻链的异质性更强。胸腔积液中κ和λ游离轻链（FLC）水平的测定显示，IgG4组和非IgG4组之间κ FLC水平（中位数：28.0对9.1mg/dl，P<0.01）和κ/λ比值（中位数：2.0对1.2，P<x0001）存在显著差异。此外，κ/λ比值与IgG4组胸膜中IgG4/I gG浆细胞比值相关。综上所述，这些结果表明IgG4参与了某些特发性胸腔积液，并为IgG4相关胸腔积液的诊断、发病机制和治疗机会提供了见解。
