Diversity Of Lymphocytes Subsets Immunophenotype In Hemophagocytic Lymphohistiocytosis Patients

Background:The Hemophagocytic Lymphohistiocytosis?HLH?is a rare but fatal disease caused by dysfunction of T cell and NK cell.Genetic defects have been identified to be associated with the development of primary HLH in pediatric patients,whereas secondary HLH?sHLH?has a much more complicated etiopathology.The underlying diseases,including neoplasia,autoimmune disease and infection,have been suggested to be major etiological factors.Due to the similarity of symptom in many disease,the identity of the stimulation of HLH could be challenging,especially at the early stage of this disease.Flow cytometry?FCM?has been used to investigate the T cell subsets of family HLH and EBV-HLH.However,the comparison of immunophenotype of different sHLH subgroups is still lacking.Objective:We aimed to investigate the proportion and MFI?The Mean fluorescence intensity?of T cell and NK cell in different subgroups of sHLH by flowcytometric analysis.Method:We included all the secondary HLH patients who were diagnosed by HLH-2004 criteria from December 2015 to December 2018.According to their underlying diseases,the patients were classified into infection-associated HLH neoplasia-associated HLH,autoimmune-associated HLH and idiopathic-associated HLH.The flow cytometry was conducted to get the immunophenotype of T cell and NK cell.After that,we use Rank Sum Test to analysis these data and try to find the differences between four HLH subgroups.Results:The immunophenotype has showed difference between subgroups in the T cell and NK cell.The percentage of NKT cells in the infection-HLH is lower than that in other groups,while the percentage of CD4⁺T cells and CD5⁺in CD4⁺T cells are higher.We also compare the FCM results of neoplasia-associated HLH patients with other groups.In the neoplasia-associated HLH patients,the percentage of CD8⁺T cell and the proportion of CD5⁺/CD7⁺cells in CD8⁺T cells are the lowest in all groups.In terms of MFI,the intensity of CD5 on T cells was also lower than that of other groups.As for the autoimmune-associated HLH patients,the percentage of CD8⁺T cells as well as the percentage of CD7⁺/CD5⁺on the CD4⁺T cell are highest in four groups,while the percentage of CD56^brightCD16^int NK cells are lower than others.Besides,the fluorescence intensity of CD7 receptor on CD4⁺T cells of patients with autoimmune diseases was significantly lower than other patients.Lastly,when comparing idiopathic-associated HLH with others,we found that the percentage of NKT cells and the MFI of CD5 on T cells both are higher than others.Conclusion:This is the first study that investigated the subsets of lymphocytes in secondary HLH patients with different underlying diseases.The results suggest that sHLH subgroups present statistical variance in several T cell and NK cell subsets.This finding could provide useful information for identifying the stimulation of HLH,as well as for choosing further active and individual treatment that may improve the outcome of HLH patients.