Complete CD16A Deficiency and Defective NK Cell Function in a Man Living with HIV

TL;DR

A man with HIV was found to have a rare genetic deficiency in CD16A, leading to impaired natural killer cell function but no severe infections.

Contribution

This case highlights novel insights into immune compensation mechanisms in CD16A deficiency despite normal HIV status.

Findings

The patient's NK cells lacked CD16A and showed no antibody-dependent cytotoxicity.

Despite CD16A deficiency, the patient had no history of severe herpes virus infections.

Monocytes and DCs in the patient were functionally similar to those in matched donors.

Abstract

A man living with HIV was found to lack expression of CD16A on his natural killer (NK) cells and monocytes. Genetic analysis revealed compound heterozygous deletion of FCGR3A, the gene encoding CD16A. The case’s NK cells showed: (a) no antibody-dependent cell-mediated cytotoxicity and very low spontaneous cytotoxicity; (b) an immature phenotype marked by high expression of CD94, CD2, NKG2A, and NKG2D, and low expression of KIR2DL2 and CD57; (c) no expression of KIR3DL1 and very low expression of FcRγ; and (d) normal cytokine production. The case’s monocytes and DCs were similar phenotypically and functionally to those from the donors matched for HIV status, age, and percentage of NK cells in the peripheral blood. In contrast to previously reported people with CD16A deficiency, this man did not have a history of severe infections with herpes viruses, suggesting that other immune cells and/or immunoregulatory function of NK cells may compensate for deficiency of cytolytic NK cells.

The online version contains supplementary material available at 10.1007/s10875-025-01886-y.

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