Identification of an Unusual Fcγ Receptor IIIa (CD16) on Natural Killer Cells in a Patient With Recurrent Infections

• Published in: Blood Vol. 88; no. 8; pp. 3022 - 3027
• Main Authors: de Vries, Esther, Koene, Harry R., Vossen, Jaak M., Gratama, Jan-Willem, von dem Borne, Albert E.G.Kr, Waaijer, Jacqueline L.M., Haraldsson, Asgeir, de Haas, Masja, van Tol, Maarten J.D.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15-10-1996
• Subjects: AIDS/HIV; CD56 Antigen - analysis; Cytotoxicity, Immunologic; Disease Susceptibility; DNA Mutational Analysis; Epitopes - genetics; Epitopes - immunology; False Negative Reactions; Fluorescent Dyes; Gene Frequency; Humans; Immunologic Deficiency Syndromes - complications; Immunologic Deficiency Syndromes - genetics; Immunologic Deficiency Syndromes - immunology; Immunophenotyping - methods; Infant, Newborn; Killer Cells, Natural - chemistry; Killer Cells, Natural - immunology; Male; Point Mutation; Polymorphism, Genetic; Receptors, IgG - analysis; Receptors, IgG - genetics; Recurrence; Respiratory Tract Infections - etiology
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V88.8.3022.bloodjournal8883022

We found an unusual Fcγ 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-Guérin (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 Leu11c/B73.1. FcγRlllb 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 FcγRIIIA 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 at position 48 in the first extracellular Ig-like domain of FcγRllla, 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 FcγRIIIA-48H/H homozygotes is required to ascertain whether this genotype is causally related to an NK cell immunodeficiency.