Establishing reference ranges for lymphocyte proliferation responses to phytohemagglutinin in patients with T cell dysfunction

Introduction: The evaluation of lymphocyte proliferation responses is a critical component of the clinical work up for patients with suspected immunodeficiencies. Those with severe combined immunodeficiency (SCID) have consistently low to absent responses (stimulation index, SI) to the mitogen phytohemagglutinin (PHA). However, patients with combined immunodeficiency (CID) have more varied proliferative responses, and are open to a wide range of interpretations. Aims: To establish lymphocyte proliferation response reference ranges for patients with T cell defects, especially those with CID as well as healthy controls. Methods: Data was collected retrospectively from charts of patients with a diagnosis of SCID (n = 39), CID (n = 52), or from healthy controls (n = 440). Reference percentiles were calculated using the 95% of the distribution of the test results. Results: The reference ranges for the control group ranged from 134 to 2220.5, whereas those with CID were distributed between 0.81 and 169.1. Patients with typical SCID had profound low proliferative responses, with SI <5. Conclusion: Our results highlight the variability of lymphocyte proliferation responses to PHA in patients with CID as well as healthy controls. These reference ranges will assist with the critical interpretation of assay results, particularly when values fall on the extreme end of the range. Statement of novelty: We provide reference ranges for lymphocyte proliferation responses to PHA from patients with CID and healthy controls.