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

Area of Science:

• Immunology
• Genetics
• Virology

Background:

• CD16A (Fc gamma receptor IIIa) is crucial for natural killer (NK) cell cytotoxicity.
• Genetic variations in FCGR3A can lead to CD16A deficiency.
• HIV infection impacts immune cell function.

Observation:

• A male HIV patient presented with a complete absence of CD16A expression on NK cells and monocytes.
• Genetic analysis identified compound heterozygous deletion of the FCGR3A gene.
• The patient's NK cells exhibited reduced antibody-dependent cell-mediated cytotoxicity (ADCC) and spontaneous cytotoxicity, alongside an immature phenotype.

Findings:

• The patient's NK cells showed altered expression of various markers including CD94, CD2, NKG2A, NKG2D, KIR2DL2, CD57, KIR3DL1, and FcRγ.
• Despite impaired NK cell cytotoxicity, monocytes and dendritic cells (DCs) remained phenotypically and functionally normal.
• Cytokine production by NK cells was unaffected.

Implications:

• This case challenges previous understandings of CD16A deficiency, as the patient did not experience severe herpes virus infections.
• Suggests potential compensatory mechanisms by other immune cells or NK cell regulatory functions in the absence of CD16A.
• Highlights the complex interplay between genetic factors, immune cell function, and susceptibility to infections in individuals with HIV.