ITK Gene Mutation: Effect on Survival of Children with Severe Hemophagocytic Lymphohistiocytosis

Hemophagocytic lymphohistiocytosis (HLH) is characterized by deadly hyperinflammatory syndrome, but data on severe HLH with multi-organ dysfunction in children are scant. The authors report a retrospective study of 8 cases with severe HLH from a pediatric intensive care unit (PICU) over a 1-y period and found that Epstein barr virus (EBV) –infection was the most common etiology. All patients had genetic analysis, which showed that four patients with EBV –infection had one homozygous mutation, c.985+75G>A (at position chr5:156667232) in exon10 of the ITK gene with poor survival rates. ITK ⁺ mutation group had higher percentages of CD3⁺CD8⁺ T cells (36.0 ± 8.4 %) than those in ITK ⁻ mutation group (28.8 ± 5.5 %), while they had similar levels of CD3⁺CD4⁺ T cells. ITK ⁺ mutation group had lower proportion of CD3⁻CD19⁺ B cells (16.3 ± 2.9 %) and CD16⁺CD56⁺ NK cells (8.4 ± 2.6 %) than ITK ⁻ mutation group (29.6 ± 5.1 % and 15.9 ± 9.0 % respectively). Most importantly, patients with EBV infection with c.985+75G>A mutation in ITK had lower survival rates than ITK ⁻ mutation group which it may be related with cellular immune dysfunction.