Fijen C A, Bredius R G, Kuijper E J, Out T A, De Haas M, De Wit A P, Daha M R, De Winkel J G
Department of Medical Microbiology, Reference Laboratory for Bacterial Meningitis, University of Amsterdam, Amsterdam, The Netherlands.
Clin Exp Immunol. 2000 May;120(2):338-45. doi: 10.1046/j.1365-2249.2000.01208.x.
Individuals with either a late (C5-9) complement component deficiency (LCCD) or properdin deficiency are at increased risk to develop meningococcal disease, often due to serogroups W135 and Y. Anti-meningococcal defence in both LCCD persons and properdin-deficient individuals without bactericidal antibodies depends mainly on phagocytosis. Three types of opsonin receptors are involved in phagocytosis by polymorphonuclear cells (PMN). These represent the polymorphic FcgammaRIIa (CD32) and FcgammaRIIIb (CD16b) receptors, and the C3 receptor CR3 (CD11b/CD18). When the distribution of FcgammaRIIa and FcgammaRIIIb allotypes was assessed in 15 LCCD and in 15 properdin-deficient patients with/without previous meningococcal disease, we found the combination of FcgammaRIIa-R/R131 with FcgammaRIIIb-NA2/NA2 allotypes to be associated with previous meningococcal disease (odds ratio 13.9, Fisher's test P = 0.036). No such relation was observed in the properdin-deficient patients. The importance of FcgammaRIIa allotypes was also demonstrated using in vitro phagocytosis assays. PMN from FcgammaRIIa-R/R131 homozygous donors internalized IgG2 opsonized meningococci W135 significantly (P < 0.05) less than PMN from FcgammaRIIa-H/H131 donors. When properdin-deficient serum was tested, it was observed that reconstitution with properdin resulted in enhanced PMN phagocytosis of the W135 meningococci (P = 0.001). This enhanced phagocytosis was parallelled by an increase in C3 deposition onto the opsonized meningococci W135 (r = 0.6568, P = 0. 01). We conclude that the occurrence of meningococcal disease in LCCD patients is associated with certain FcgammaR allotypes. Properdin-deficient individuals are susceptible to meningococcal disease because of an insufficient C3 deposition on the surface of meningococci, resulting in insufficient phagocytosis.
患有晚期（C5 - 9）补体成分缺乏症（LCCD）或备解素缺乏症的个体患脑膜炎球菌病的风险增加，这通常是由W135和Y血清群引起的。在LCCD患者和没有杀菌抗体的备解素缺乏个体中，抗脑膜炎球菌防御主要依赖于吞噬作用。三种调理素受体参与多形核细胞（PMN）的吞噬作用。这些受体分别是多态性FcγRIIa（CD32）和FcγRIIIb（CD16b）受体，以及C3受体CR3（CD11b/CD18）。当在15例LCCD患者以及15例有/无既往脑膜炎球菌病的备解素缺乏患者中评估FcγRIIa和FcγRIIIb同种异型的分布时，我们发现FcγRIIa - R/R131与FcγRIIIb - NA2/NA2同种异型的组合与既往脑膜炎球菌病相关（优势比13.9，Fisher检验P = 0.036）。在备解素缺乏患者中未观察到这种关系。使用体外吞噬试验也证明了FcγRIIa同种异型的重要性。来自FcγRIIa - R/R131纯合供体的PMN内化IgG2调理的W135脑膜炎球菌的能力明显（P < 0.05）低于来自FcγRIIa - H/H131供体的PMN。当检测备解素缺乏血清时，观察到用备解素重建可增强PMN对W135脑膜炎球菌的吞噬作用（P = 0.001）。这种增强的吞噬作用与C3在调理的W135脑膜炎球菌上的沉积增加平行（r = 0.6568，P = 0.01）。我们得出结论，LCCD患者中脑膜炎球菌病的发生与某些FcγR同种异型相关。备解素缺乏个体易患脑膜炎球菌病是因为脑膜炎球菌表面的C3沉积不足，导致吞噬作用不足。
