Normal B-cell ranges in infants: A systematic review and meta-analysis

During the first year of life, B-cell level is a valuable indicator of whether external factors, such as exposure to B-cell-depleting therapies, have an adverse impact on immune system development. However, there are no standard reference ranges of B-cell levels in healthy infants by age.Our aim was to estimate the normal range of B-cell levels in infants, by age, during the first year of life by pooling data from published studies.Studies reporting B-cell levels measured by using flow cytometry and CD19 markers in healthy infants were identified via a systematic literature review. Quality and feasibility assessments determined suitability for inclusion in meta-analyses by age group and/or continuous age. Means and normal ranges (2.5th-97.5th percentile) were estimated for absolute and percentage B-cell levels. Sensitivity analyses assessed the impact of various assumptions.Of the 37 relevant studies identified, 28 were included in at least 1 meta-analysis. The means and normal ranges of B-cell levels were found to be 707 cells/μL in cord blood (range 123-2324 cells/μL), 508 cells/μL in infants aged 0 to 1 month (range 132-1369 cells/μL), 1493 cells/μL in infants aged 1 to 6 months (range 416-3877 cells/μL), and 1474 cells/μL in infants older than 6 months (range 416-3805 cells/μL). The continuous age model showed that B-cell levels peaked at week 26. Trends were similar for the percentage B-cell estimates and in sensitivity analyses.These meta-analyses provide the first normal reference ranges for B-cell levels in infants, by week of age, during the first year of life.