A defect of CD16-positive monocytes can occur without disease

Area of Science:

• Immunology
• Human Genetics

Background:

• CD16-positive monocytes, including nonclassical and intermediate subsets, were first identified in 1988.
• No prior reports documented selective defects in the number of these specific monocyte populations in blood.

Purpose of the Study:

• To investigate a family with an apparent absence of CD16-positive monocytes.
• To determine the clinical implications of lacking CD16-positive monocyte subsets.

Main Methods:

• Flow cytometry was used to quantify monocyte subsets in peripheral blood.
• Genetic analysis was performed to screen for mutations in candidate genes, including M-CSF and M-CSFR.
• Clinical evaluation of affected family members was conducted.

Main Results:

• Three out of four siblings were found to completely lack CD16-positive monocyte subsets (nonclassical and intermediate).
• These individuals had ≤2 CD16-positive monocytes/μl, compared to 52±18 cells/μl in healthy controls.
• The index case presented with recurrent pleural effusion, infections, and signs of autoinflammation, but no mutations in relevant genes were identified.
• The other two siblings lacking these monocytes were asymptomatic.
• Serum M-CSF levels were normal, and no mutations in M-CSF or M-CSFR genes were found.

Conclusions:

• The absence of CD16-positive monocytes in blood does not appear to be inherently pathogenic.
• This finding challenges the presumed necessity of CD16-positive monocyte subsets for normal health.
• Further research is warranted to understand the precise role and regulation of these monocyte populations.