IgG亚类抗体在慢性感染中的作用：以囊性纤维化为例。

The role of IgG subclass antibodies in chronic infection: the case of cystic fibrosis.

作者信息

Moss R B

机构信息

Department of Pediatrics, Stanford University Medical School, CA.

出版信息

N Engl Reg Allergy Proc. 1988 Jan-Feb;9(1):57-61. doi: 10.2500/108854188778984491.

DOI:10.2500/108854188778984491

Abstract

Our studies have revealed that patients with Cystic Fibrosis CF who are infected with P. aeruginosa have grossly elevated serum levels of IgG antibodies to the opsonic immunodeterminant, type-specific LPS. Second, this elevation is distributed among all four IgG subclasses, with a significant shift towards IgG3. Third, sera from colonized CF patients shows diminished opsonic capacity, although complement dependent human neutrophil phagocytosis is not notably impaired. Fourth, functional polyclonal or monoclonal antibody opsonins exhibit prozone inhibition of phagocytosis at high concentrations. Fifth, sera from uninfected CF patients have lower levels and proportions of IgG2 antibodies to P. aeruginosa LPS, and higher levels and proportions of IgG4 antibodies, than normal controls. Finally, levels of IgG4 antibodies, but not IgG1, 2, or 3, correlate inversely with opsonic capacity. We therefore make several speculations. High levels of IgG4 antibodies to opsonic immunodeterminants may inhibit normal pulmonary clearance of P. aeruginosa by alveolar macrophages in vivo. Second, high levels of opsonic antibodies may also contribute to the problem in vivo by the phenomenon of prozone inhibition. Third, reduced levels of IgG2 antibodies in uninfected CF patients raises the intriguing possibility of an wider polysaccharide antigen-related isotype-restricted immunodeficiency, with an attempted compensatory shift to IgG4 doomed to failure.

摘要

我们的研究表明，感染铜绿假单胞菌的囊性纤维化（CF）患者血清中针对调理素免疫决定簇（型特异性脂多糖）的IgG抗体水平显著升高。其次，这种升高分布于所有四种IgG亚类中，且明显向IgG3偏移。第三，定植CF患者的血清显示调理能力下降，尽管补体依赖的人中性粒细胞吞噬作用未受到明显损害。第四，功能性多克隆或单克隆抗体调理素在高浓度时表现出吞噬作用的前带抑制。第五，与正常对照相比，未感染CF患者的血清中针对铜绿假单胞菌脂多糖的IgG2抗体水平和比例较低，而IgG4抗体的水平和比例较高。最后，IgG4抗体水平与调理能力呈负相关，而IgG1、2或3则不然。因此，我们做出了几种推测。针对调理素免疫决定簇的高水平IgG4抗体可能会在体内抑制肺泡巨噬细胞对铜绿假单胞菌的正常肺清除。其次，高水平的调理抗体也可能通过前带抑制现象在体内导致问题。第三，未感染CF患者中IgG2抗体水平降低，这引发了一种有趣的可能性，即存在更广泛的多糖抗原相关的同种型限制性免疫缺陷，试图向IgG4进行代偿性转变注定会失败。