Granulocyte/macrophage-colony-stimulating factor autoantibodies and myeloid cell immune functions in healthy subjects
Granulocyte/macrophage-colony-stimulating factor autoantibodies and myeloid cell immune functions in healthy subjects
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DOI：
10.1182/blood-2008-05-155689
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发表时间：
2009-03-12
期刊：
影响因子：
20.3
通讯作者：
Trapnell, Bruce C.
中科院分区：
文献类型：
--
作者：
Uchida, Kanji;Nakata, Koh;Trapnell, Bruce C.
高水平的粒细胞/巨噬细胞集落刺激因子(GM-CSF)自身抗体被认为是导致肺泡蛋白沉积症(PAP)的原因，这是一种罕见的综合征，其特征是髓系功能障碍导致肺表面活性物质积聚和呼吸衰竭。矛盾的是，GM-CSF自身抗体在健康人中很少出现，通常在从健康人的血清中提纯的药物静脉免疫球蛋白(IVIG)中出现。这些发现表明，GM-CSF自身抗体通常存在于难以检测到的低水平健康人中，或者用于IVIG纯化的血清池可能包括高水平GM-CSF自身抗体的无症状患者。使用几种实验方法，在所有健康受试者(n=72)中检测到GMCSF自身抗体，水平低，足以对多种髓系功能进行静流变调节。血清GMCSF比以往报道的更丰富，但超过99%的血清被GM-CSF自身抗体结合和中和。确定了与PAP发生相关的GM-CSF自身抗体的临界阈值。结果表明，血清游离GM-CSF水平维持在较低水平，确定了一种新的潜在的天然免疫调节机制，有助于确定GMCSF自身抗体用于治疗炎症性和自身免疫性疾病的治疗窗口，并可能在PAP的发病机制中发挥作用。(血。2009；113：2547-2556)
High levels of granulocyte/macrophage colony-stimulating factor (GM-CSF) autoantibodies are thought to cause pulmonary alveolar proteinosis (PAP), a rare syndrome characterized by myeloid dysfunction resulting in pulmonary surfactant accumulation and respiratory failure. Paradoxically, GM-CSF autoantibodies have been reported to occur rarely in healthy people and routinely in pharmaceutical intravenous immunoglobulin (IVIG) purified from serum pooled from healthy subjects. These findings suggest that either GM-CSF autoantibodies are normally present in healthy people at low levels that are difficult to detect or that serum pooled for IVIG purification may include asymptomatic persons with high levels of GM-CSF autoantibodies. Using several experimental approaches, GMCSF autoantibodies were detected in all healthy subjects evaluated (n = 72) at low levels sufficient to rheostatically regulate multiple myeloid functions. Serum GMCSF was more abundant than previously reported, but more than 99% was bound and neutralized by GM-CSF autoantibody. The critical threshold of GM-CSF autoantibodies associated with the development of PAP was determined. Results demonstrate that free serum GM-CSF is tightly maintained at low levels, identify a novel potential mechanism of innate immune regulation, help define the therapeutic window for potential clinical use of GMCSF autoantibodies to treat inflammatory and autoimmune diseases, and have implications for the pathogenesis of PAP. (Blood. 2009; 113:2547-2556)