Age-stratified CD19⁺ B cell reference values in children and adolescents -a systematic review and meta-analysis

Accurate monitoring of B-cell reconstitution is dependent on age-specific pediatric reference ranges. However, pediatric CD19⁺ B-cell reference values currently lack harmonization and remain inconsistently defined.

To systematically evaluate published pediatric reference values for CD19⁺ B cells in healthy children and adolescents (0-18 years).

This review and meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. A comprehensive literature search was performed for studies reporting CD19⁺ B cells in healthy pediatric controls from year 2000 to 2025 (final search in March 2025). Records were independently screened and assessed for quality by three investigators. Data for lower limit of normal (lower limit of the 95% reference interval) were analyzed and compared for different age groups.

After screening, 29 publications met the inclusion criteria, representing a total cohort of 10,399 individuals. Our analysis shows that the lower limit of normal of CD19⁺ B-cell values differ according to the age of the child. We propose five distinct age groups and corresponding values of lower limit of normal. For children below 6 years of age, B-cell values are consistently different from what has been reported for adult patients.

This systematic synthesis summarizes consolidated age-stratified lower limits of normal values for CD19⁺ B cells in children and adolescents. Proposed CD19⁺ B values can be used for standardized clinical monitoring of B-cell recovery to normal values after CD19-depleting therapy.