Why does the autoantibody against cytokine incease in patients with idiopathic pulmonary alveolar proteinosis?

最近的研究表明，PAP患者的中性粒细胞的基本功能，如吞噬作用、细胞粘附、H_2O_2产生和微生物杀伤功能降低（Uchida，et. Al.. NEJM. 2007）。相反，我们发现，与正常对照组相比，外周血T和B细胞的某些亚群被激活或过度成熟。在CD 4 ^+细胞中，初始T细胞的数量减少，效应记忆/初始比例上调。有趣的是，少量的CD 4 ^+细胞在没有任何刺激的情况下离体增殖。在B细胞中，与对照组相比，初始和记忆B细胞亚群中的CD 38 ^+活化细胞增加，而CD 19的表达减少。表达CD 138（浆细胞标志物）的细胞显著增加。重要的是，在没有任何刺激的情况下孵育2天后，在外周血单个核细胞的培养上清液中检测到GM-CSF自身抗体。这些结果表明，T和B细胞的某些亚群被驱动成熟/活化，并可能促进产生自身抗体。

Recent studies have revealed that neutrophils from PAP patients had reduced basal functions such as phagocytosis, cell-adhesion, H_2O_2 production, and microbial killing (Uchida, et. Al.. NEJM.2007). In contrast, we found that some subsets of peripheral blood T and B cells were activated or excessively matured compared to normal controls. In CD4^+ cells, the number of naive T cells was reduced and the effecter-memory/naive ratio was up-regulated. Interestingly, small amount of CD4^+ cells were proliferating ex vivo without any stimulation. In B cells, CD38^+ activated cells were increased in both naive and memory B cell subset, whereas the expression of CD19 was reduced compared to the controls. Cells expressing CD138, a plasma cell marker, were significantly increased. Importantly, GM-CSF autoantibody was detected in the culture supernatants of peripheral blood mononuclear cells after 2 days incubation without any stimulation. These results suggested that some subsets of T and B cells were driven to be matured/activated and possibly promoted to produce the autoantibody.