Identification of an unusual Fc gamma receptor IIIa (CD16) on natural killer cells in a patient with recurrent infections

Abstract

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-Geerin (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.

Deficiency in circulating natural killer (NK) cell subsets in common variable immunodeficiency and X-linked agammaglobulinaemia

“…These results agree with our finding of increased CD57 1 cells in CVID patients and are consistent with the concept of a more inflammatory pattern of pathology [24]. Although circulating NK cell numbers are clearly depleted in CVID patients, this appears to have no short-term clinical relevance, since the patients are not prone to herpes viruses, as has been reported in rare patients with isolated NK cell deficiencies [25], nor to most other viral infections. Furthermore, previous studies on in vitro cytotoxicity of PBMC from CVID patients to the K562 cell line (presumed NK activity) have been normal, suggesting a compensatory mechanism for the low numbers [4].…”

Fcγ receptor polymorphisms in relation to periodontitis

“…Similar analyses for FcgRIIIa and IIIb polymorphisms showed no differences between the V1 and F/F158, and NA21 and NA1/NA1 genotypes, respectively (data for FcgRIIIa also shown in Fig. 1); the numbers of teeth within the different bone loss categories were in all these cases essentially similar to the values presented in (Kobayashi et al 1997, Kobayashi et al 2000, Kobayashi et al 2001, Meisel et al 2001), viral diseases (De Vries et al 1996) and the Guillain-Barré syndrome . The present study was designed to investigate whether polymorphisms in FcgR showed an altered prevalence or were associated with severity among periodontitis patients from strictly Northern European heritage (Dutch), in comparison to controls without destructive periodontitis.…”

Eight-color immunophenotyping of T-, B-, and NK-cell subpopulations for characterization of chronic immunodeficiencies

“…NK-cell defects present with a heterogeneous clinical phenotype and are difficult to be detected by plain measurement of total NK-cell numbers. However, patients with defects in the NK-cell system exhibit characteristic NK-cell signatures with normal NK-cell numbers but inactive function due to deletions in specific receptors (e.g., in TAP-2 deficient patients), a reduced cytotoxicity (e.g., familial lymphohistiocytosis syndromes, Hermansky-Pudlak syndrome, or Papillon-Lefevre syndrome) or due to CD16 impairment (4,(58)(59)(60). It is of importance to determine NK cells by gating CD16 versus CD56 and not by using a combined CD16/56 marker or by use of CD56 alone.…”