Fig. 2

Clinical, genetic and functional characteristics of the patients included in the prospective cohort. a Heatmap of clinical and functional features of the implementation cohort in relation to HLH-2004 diagnostic criteria [2]. The patients are ordered based on age at diagnosis of HLH. A family history refers to a positive family history for HLH or unexplained siblings’ death in childhood. b The different molecular diagnoses achieved in the prospective cohort according to age group at diagnosis of HLH. c NK cell cytotoxic activity, displayed as lytic units at 25 % specific lysis, in healthy controls and patients from the implementation cohort grouped in diagnosed (n = 10) and undiagnosed (n = 13) (significance level *p < 0.05, ****p < 0.0001). d Intracellular expression of perforin, CD107a, granzyme A and B, and SAP in PBMCs of HLH patients from the implementation cohort. Patients are grouped by their molecular diagnosis (FHL2, n = 4; FHL3-4,GS2,CHS, n = 9; No diagnosis, n = 19). The data are expressed as percentage of normalized median fluorescence intensity (MFI) in comparison with healthy controls. Exocytic activity of CD3⁻CD56⁺ NK cells (e) and CD8⁺CD57⁺ T cells (f) was measured as percentage of CD107a⁺ cells in healthy controls and HLH patients from the implementation cohort. P815 target cells were used alone and in combination with anti-CD16 antibody for NK cells and anti-CD3 antibody for CD8 T cells. Exocytic activity of NK cells was also measured using K562 target cells. Patients are grouped by their molecular diagnosis (FHL2, n = 4; FHL3-4,GS2,CHS, n = 9; No diagnosis, n = 20). The controls used were both local and transport controls