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SUMMARY OBJECTIVE: The purpose of this study was to assess the association between clinical, laboratory, and functional analyses and polymorphism in the FCGR3A gene in individuals with functional NK cell deficiency. METHODS: A total of 15 functional NK cell deficiency patients and 10 age-matched healthy controls underwent NK cell subgroup, cytotoxicity, and FCGR3A whole-exome analysis with next-generation sequencing. RESULTS: Three different NK cell subsets (CD56brightCD16neg, CD56brightCD16int, and CD56dimCD16hi) were identified. No statistically significant difference was found in the ratio of CD56brightCD16neg cells between patients and controls. CD56brightCD16int and CD56dimCD16hi ratios were found to be significantly lower in patients. As a result of NK cell cytotoxicity analysis, a proportional decrease of K562 amount between patients and controls was found to be statistically significant (p<0.001). In the FCGR3A whole-exome analysis, all patients were found to be homozygous mutant for the c.526G > T (p.V176F) in exon 4, while three patients were homozygous wild type and 12 patients were heterozygous for the c.197T>A (p.L66H) in exon 3. CONCLUSION: In this study, a group of pediatric patients with suspected functional NK cell deficiency were evaluated and the findings indicated that NK subsets, cytotoxicity results, and FCGR3A gene polymorphism were found to be correlated with the clinical features. We conclude that this kind of study might contribute to follow-up the patients in time.
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Objective To investigate the effect of FCGR3A polymorphisms on NK cell function. Methods Peripheral blood samples from can?cer patients were collected and FCGR3A polymorphisms were confirmed by PCR. In vitro proliferation rates,ADCC activity,and expression of NK cell activating receptors were compared under trastumab stimulation. Results This study showed that the wild?type FCGR3A exhibited a higher affinity to trastumab along with better NK cell proliferation and ADCC activity than the mutant type. Compared to the patients with wild?type FC?GR3A,the proliferation rates of NK cells in patients with the mutant type were reduced by approximately 8?fold. In addition,the expression of NK cell activating receptors in patients with wild?type FCGR3A was higher than in patients with the mutant type. Conclusion Mutations in FC?GR3Areduce NK cell function,causing a poor reaction to monoclonal antibody.