Correlation of T Cell Receptor Excision Circles With CD4 T-Lymphocyte Levels Post Haematopoietic Stem Cell Transplant for Severe Combined Immunodeficiency

Introduction Newborn screening for severe combined immune deficiency (SCID) has recently been introduced across Australia. Variability exists across sites in terms of the assays and methods used for analysis. This makes comparison of data across sites difficult when determining reference ranges and decision limits. This lack of uniformity also exists internationally and necessitates regular in-house review of decision limits to ensure correct identification of true cases. Method We collected paired blood spot cards and flow cytometry samples from an infant undergoing hematopoietic stem cell transplant (HSCT) for SCID to monitor T cell recovery post-transplant. T cell receptor excision circles (TRECs), absolute CD4 counts, and naïve CD4 percentages were assessed at one to two monthly intervals for twelve months post-transplantation. Results All TREC values less than 50 per 105 cells (our institution’s decision limit for urgent immunology referral) correlated to a clinically significant decreased absolute CD4 count and decreased naïve CD4 T cell percentage. TREC values greater than 275 per 105 cells, (our institutions lower limit of normal range cutoff; corresponding 0.1 percentile of term babies) correlated to normal age-appropriate flow cytometry values. However, TREC values between 275 and 50 per 105 cells (our upper and lower decision limits for decreased TRECs) correlated variably, with both normal and decreased absolute and naïve CD4 values seen with TRECs in this range. Conclusion Longitudinal follow-up in this patient showed a strong correlation between bloodspot TREC analysis and CD4 values via flow cytometry. Correlation was strongest for undetectable TREC values and where TREC levels were within normal range. Further data are needed to explore the upper and lower decision limits for decreased TREC values in order to allow for detection of clinically significant T cell lymphopenia whilst limiting the number of false-positive cases identified.