Immundeficiency 20D84.1

Autosomal Recessive Primary Immunodeficiency with Defective Spontaneous Natural Killer Cell Cytotoxicity; Autosomal Recessive Primary Immunodeficiency with Defective Spontaneous Nk Cell Cytotoxicity; Cd16 Deficiency; Immunodeficiency, Type 20 (OMIM: 615707). This disease is associated with mutations in the FCGR3A gene.

Jawahar et al (1996) reported on a 5-year-old girl with primary immunodeficiency. She originally presented in infancy with recurrent otitis media and sinusitis and recurrent herpesvirus infections. The number of circulating NK cells was decreased, and the circulating cells expressed a mutant CD16 protein, as revealed by antibody testing. Examination of NK cell function showed significantly decreased spontaneous cytotoxicity but preserved antibody-dependent cellular cytotoxicity (ADCC). The number and function of other circulating immune cells was normal, indicating an isolated NK defect.

De Vries et al (1996) reported on a 3-year-old boy who suffered from recurrent viral respiratory infections since birth. The child had also had severe problems with BCG vaccination and with Epstein-Barr virus and varicella-zoster virus infections. Laboratory tests revealed normal numbers of NK cells, and in vitro functional studies of the patient's cells were normal. However, the patients' NK cells had an unusual CD16 phenotype, and De Vries et al. (1996) postulated in vivo NK cell dysfunction.

Grier et al. (2012) reported a 14-year-old boy with recurrent EBV-related Castleman disease in the lymph nodes that began at age 10 years. He later developed papillomavirus in the hands and feet. Immunologic examination revealed no abnormalities; the percentage of circulating NK cells was within the normal range. Both the patient's and control NK cells were recognized by an anti-CD16 monoclonal antibody to the 3G8 epitope, indicating that the CD16 molecule was expressed. However, only control NK cells were recognized by another anti-CD16 antibody that recognized the specific B73.1 epitope, indicating a defect of CD16.

1. de Vries et al.(1996) Identification of an unusual Fc-gamma receptor IIIa (CD16) on natural killer cells in a patient with recurrent infections. Blood 88: 3022-3027.
2. Grier JT et al (2012) Human immunodeficiency-causing mutation defines CD16 in spontaneous NK cell cytotoxicity. J Clin Invest 122: 3769-3780.
3. Jawahar S et al (1996) Natural killer (NK) cell deficiency associated with an epitope-deficient Fc receptor IIIA (CD16-II). Clin Exp Immun 103: 408-413.