de Vries E, Koene H R, Vossen J M, Gratama J W, von dem Borne A E, Waaijer J L, Haraldsson A, de Haas M, van Tol M J
Department of Pediatrics, Leiden University Hospital, The Netherlands.
Blood. 1996 Oct 15;88(8):3022-7.
We found an unusual fc gamma receptor IIIa (CD16) phenotype on the natural killer (NK) cells of a 3-year-old boy, who suffered from recurrent viral respiratory tract infections since birth. He also had severe clinical problems after Bacille Calmette-Geérin (BCG) vaccination and following Epstein-Barr virus and Varicella Zoster virus infections. His peripheral blood lymphocytes contained a normal percentage and absolute number of CD3-CD7+ cells, which were positively stained with the CD16 monoclonal antibodies (MoAbs) 3G8 and CLBFcRgran1, but did marginally stain with the CD16 MoAb Lau11c/B73.1. Fc gamma RillIb expression on granulocytes appeared to be normal. NK cell function, analyzed in vitro by direct cytotoxicity on K562 target cells and ADCC-activity on P815 target cells, was normal compared with an age-matched healthy control. Sequence analysis of the Fc gamma RIIIA gene, encoding CD16 on NK cells and macrophages, showed a T to A nucleotide substitution at position 230 on both alleles, predicting a leucine (L) to histidine (H) amino acid change position 48 in the first extracellular lg-like domain of Fc gamma RIIIa, which contains the Leu11c/B73.1 epitope. The combined use of CD16 and CD56 MoAbs labeled with the same fluorescent dye, as often applied in routine immunophenotyping procedures, will leave these homozygotes undiagnosed. The pattern of infections in this patient is in agreement with the postulated function of NK cells in the immunological defense against viruses and other intracellular microorganisms. Further analysis of the NK cell function in vitro and follow-up of the clinical course of Fc gamma RIIIA-48H/H homozygotes is required to ascertain whether this genotype is causally related to an NK cell immunodeficiency.
我们在一名3岁男童的自然杀伤（NK）细胞上发现了一种不寻常的Fcγ受体IIIa（CD16）表型，该男童自出生以来反复发生病毒性呼吸道感染。他在接种卡介苗（BCG）后以及感染爱泼斯坦-巴尔病毒和水痘带状疱疹病毒后也出现了严重的临床问题。他的外周血淋巴细胞中CD3-CD7+细胞的百分比和绝对数量正常，这些细胞被CD16单克隆抗体（MoAbs）3G8和CLBFcRgran1阳性染色，但与CD16 MoAb Lau11c/B73.1仅有微弱染色。粒细胞上的FcγRIIIb表达似乎正常。通过对K562靶细胞的直接细胞毒性和对P815靶细胞的ADCC活性在体外分析NK细胞功能，与年龄匹配的健康对照相比正常。编码NK细胞和巨噬细胞上CD16的FcγRIIIA基因的序列分析显示，两个等位基因在第230位核苷酸处发生了T到A的替换，预测在FcγRIIIa的第一个细胞外lg样结构域中第48位氨基酸由亮氨酸（L）变为组氨酸（H），该结构域包含Leu11c/B73.1表位。在常规免疫表型分析程序中经常使用的用相同荧光染料标记的CD16和CD56 MoAbs的联合使用，会使这些纯合子无法被诊断出来。该患者的感染模式与NK细胞在针对病毒和其他细胞内微生物的免疫防御中的假定功能一致。需要进一步体外分析NK细胞功能并对FcγRIIIA-48H/H纯合子的临床病程进行随访，以确定该基因型是否与NK细胞免疫缺陷有因果关系。
