CD20 molecule deficiency and carrier frequency: a village-based screening study

CD20 deficiency is an autosomal recessive inborn error of immunity (IEI), and the only known affected individual worldwide has been under follow-up in our clinic. Because the consanguineous parents of the index patient are putative carriers, we hypothesized that additional individuals with reduced CD20 expression might exist within their village population. This study aimed to evaluate clinical features associated with IEI and to identify individuals displaying CD20 mean fluorescence intensity (MFI) patterns consistent with putative carrier status, while also providing appropriate genetic counseling.

This cross-sectional screening study was conducted in December 2024 in Çukurbağ village. Participants completed a questionnaire that included IEI warning signs and information about their familial relationship to the index case. CD19 and CD20 expression in peripheral blood samples was analyzed by flow cytometry. Individuals were classified as putative carriers if their CD20 MFI values were <50% of those of healthy controls.

A total of 145 individuals (44 children, 101 adults) from 52 families were screened. Among individuals related to the index case, the consanguinity rate was 39.3%. Jeffrey Modell Foundation scores were significantly higher in children than in adults (p < 0.05). No individuals with CD20 deficiency were identified. Approximately 10% of participants (n = 14) exhibited normal CD19 and CD20 percentages but showed reduced CD20 MFI values consistent with putative carrier status. All putative carriers were relatives of the index case. The proposed CD20-A700 (≤2537) and CD20-FITC (≤7787) MFI thresholds demonstrated high diagnostic performance (sensitivity and specificity values are presented for both parameters).

CD20 MFI, rather than CD20 percentage, appears to be a more informative indicator for identifying individuals with flow-cytometric patterns suggestive of putative carrier status. Flow cytometry may serve as a rapid and practical preliminary screening tool in community-based settings; however, confirmation of carrier status requires molecular genetic testing, and genetic counseling should be based on verified genotypic results.