Double negative alpha beta T cells in pediatric hemophagocytic syndromes

Introduction: Autoimmune lymphoproliferative syndrome (ALPS) and hemophagocytic lymphohistiocytosis (HLH) share clinical and laboratory features including lymphadenopathy, splenomegaly, and pancytopenia. We sought to measure αβ double negative T cells (αβ DNT) in a group of patients with established diagnosis of HLH in relation to disease activity and severity. Methods: We conducted a follow-up, controlled study that comprised 25 patients with HLH and 25 healthy matched controls. Patients were subjected to clinical evaluation and flowcytometric measurement of αβ DNT Cells at presentation and 9 weeks after start of HLH induction treatment. Results: In 17 (68%) patients, infection was the trigger of HLH while the cause was malignancy in three (12%), and rheumatological disorders in two patients (8%). At enrollment, 15 patients (60%) had αβ DNT cells levels [median (IQR): 1.71 (1.25-2.12)] that were significantly higher than the control values [median (IQR): 0.7 (0.4-0.8)] (p<0.001). The αβ DNT counts of patients were also higher at enrollment as compared to values at the end of week 9 [median (IQR): 0.76 (0.45-1.17)]; p=0.018. Survivors (n=8) and non-survivors (n=17) had comparable levels of αβ DNT cells at enrollment (p=0.861). αβ DNT cell count correlated positively with ALT (p=0.019) and negatively with CD4/CD8 ratios (p=0.023). Conclusion: Elevated αβ DNT cell counts might be related to the HLH process and this implies that mild elevation can exist in HLH and are not specific to ALPS. Wider scale studies with longer periods of follow up are needed to validate the results and properly outline the correlation between both medical conditions. Keywords: Hemophagocytic lymphohistiocytosis, Double negative T cells, mortality, ALPS