de Haas M, Kleijer M, van Zwieten R, Roos D, von dem Borne A E
Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, University of Amsterdam, The Netherlands.
Blood. 1995 Sep 15;86(6):2403-13.
Several individuals have been described whose neutrophils lack the normally abundantly expressed IgG Fc gamma receptor IIIb (Fc gamma RIIIb). We now studied the responsible genomic defect and analyzed the medical history in detail of 21 Fc gamma RIIIb-negative donors identified in 14 unrelated families. We developed a polymerase chain reaction allele-specific-primer annealing assay to genotype for the NA polymorphism of the Fc gamma RIIIB gene. All Fc gamma RIIIb-deficient individuals were negative for both the NA1 and the NA2 allele. In all cases the complete absence of the Fc gamma RIIIB alleles was confirmed using a Southern blot-based restriction fragment length polymorphism assay. Furthermore, an additional deletion of the next more telomeric located Fc gamma RIIC gene was found. Family studies showed that at least one Fc gamma RIIIB allele was absent in both parents in 6 families, whereas in 2 families the father had a normal phenotype. Two individuals suffered from an autoimmune thyroiditis. Four individuals had had multiple episodes of infection, 3 had only incidental infections, and 14 never had any serious infection. Genotyping showed a normal Fc gamma RIIa phenotype distribution among the Fc gamma RIIIb-negative individuals, thus excluding the possibility that the presence of the favorable IgG2-binding low-responder isoform of Fc gamma RIIa (131-H) contributed to the overall absence of recurrent bacterial infections.
已有数例报告称，某些个体的中性粒细胞缺乏正常情况下大量表达的免疫球蛋白G Fcγ受体IIIb（FcγRIIIb）。我们现研究了相关的基因缺陷，并详细分析了在14个无亲缘关系的家庭中确定的21名FcγRIIIb阴性供体的病史。我们开发了一种聚合酶链反应等位基因特异性引物退火分析法，用于对FcγRIIIB基因的NA多态性进行基因分型。所有FcγRIIIb缺陷个体的NA1和NA2等位基因均为阴性。在所有病例中，使用基于Southern印迹的限制性片段长度多态性分析证实了FcγRIIIB等位基因完全缺失。此外，还发现了下一个位于端粒更远处的FcγRIIC基因的额外缺失。家族研究表明，6个家庭的父母双方至少有一个FcγRIIIb等位基因缺失，而在2个家庭中，父亲表现型正常。2名个体患有自身免疫性甲状腺炎。4名个体曾多次发生感染，3名仅有偶发性感染，14名从未发生过任何严重感染。基因分型显示，在FcγRIIIb阴性个体中，FcγRIIa的表型分布正常，因此排除了FcγRIIa（131-H）有利的IgG2结合低反应性同种型的存在导致反复细菌感染总体缺失的可能性。
