IgM-type GM-CSF autoantibody is etiologically a bystander but associated with IgG-type autoantibody production in autoimmune pulmonary alveolar proteinosis.
IgM-type GM-CSF autoantibody is etiologically a bystander but associated with IgG-type autoantibody production in autoimmune pulmonary alveolar proteinosis.
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DOI：
10.1152/ajplung.00378.2011
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发表时间：
2012-05
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通讯作者：
T. Nei;S. Urano;N. Motoi;J. Takizawa;C. Kaneko;H. Kanazawa;R. Tazawa;K. Nakagaki;K. Akagawa;K. Akasaka;T. Ichiwata;A. Azuma;K. Nakata
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作者：
T. Nei;S. Urano;N. Motoi;J. Takizawa;C. Kaneko;H. Kanazawa;R. Tazawa;K. Nakagaki;K. Akagawa;K. Akasaka;T. Ichiwata;A. Azuma;K. Nakata
粒细胞-巨噬细胞集落刺激因子（GM-CSF）自身抗体（GMAb）是自身免疫性肺泡蛋白沉积症（aPAP）的病原体。它主要由IgG同种型组成。目前，关于该自身抗体的其他同种型的信息有限。我们在80%以上的aPAP患者和22%的健康受试者中检测到血清IgM同种型GMAb（IgM-GMAb），表明大多数患者可能存在持续的抗原压力。IgM同种型水平与IgG-GMAb水平弱相关，但与IgA-GMAb无关，表明其产生可能与IgG-GMAb相关。IgM同种型对GM-CSF的平均结合亲合力比IgG-GMAb同种型低100倍，而中和能力的IC（50）值比IgG-GMAb高20，000倍，表明IgM-GMAb仅是GM-CSF的非常弱的中和剂。在9例患者的支气管肺泡灌洗液中，始终检测到IgG-GMAb，但大多数患者的IgM-GMAb低于检测限，证实IgM-GMAb在aPAP发病机制中具有旁观者功能。相反，它可能参与体内IgG-GMAb的形成机制。
The granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibody (GMAb) is the causative agent underlying autoimmune pulmonary alveolar proteinosis (aPAP). It consists primarily of the IgG isotype. At present, information on other isotypes of the autoantibody is limited. We detected serum the IgM isotype of GMAb (IgM-GMAb) in more than 80% of patients with aPAP and 22% of healthy subjects, suggesting that a continuous antigen pressure may be present in most patients. Levels of the IgM isotype were weakly correlated with IgG-GMAb levels but not IgA-GMAb, suggesting that its production may be associated with that of IgG-GMAb. The mean binding avidity to GM-CSF of the IgM isotype was 100-fold lower than the IgG-GMAb isotype, whereas the IC(50) value for neutralizing capacity was 20,000-fold higher than that of IgG-GMAb, indicating that IgM-GMAb is only a very weak neutralizer of GM-CSF. In bronchoalveolar lavage fluid from nine patients, IgG-GMAb was consistently detected, but IgM-GMAb was under the detection limit in most patients, confirming that IgM-GMAb is functionally a bystander in the pathogenesis of aPAP. It rather may be involved in the mechanism for development of IgG-GMAb in vivo.