Hemophagocytic syndrome: Laboratory and molecular characterization

Abstract

Abstract: BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening syndrome of fever, cytopenia, and organomegaly resulting from immune activation and cytokine storm. The syndrome can occur as a primary/familial form mostly affecting infants and young children or as an acquired form secondary to an underlying pathology (infection, malignancy, and autoimmune disease) that may have an underlying genetic predisposition, including mutations or polymorphisms. PATIENTS AND METHODS: This case–control study was conducted in Basra, Iraq. Thirty-four pediatric and adult patients with peripheral cytopenia attributed to bone marrow (BM) hemophagocytosis enrolled with 34 healthy individuals (age and sex matched) included as a control group. Whole blood was tested for complete blood count and screened for the presence of mutations in the perforin gene by polymerase chain reaction amplification; in addition, serum samples were tested for soluble CD25, ferritin, and triglycerides (TGs). RESULTS: The mean hemoglobin level and platelets count were significantly lower in HLH patients compared to the control group (P < 0.001), while there was no significant statistical difference regarding neutrophils count (P > 0.05). Soluble CD25 (s.IL-2R) testing revealed inconsistent results; serum ferritin and TGs were significantly higher in HLH patients compared to the control group (P < 0.001). About nine cases were genetically proven to have primary HLH; all were infants under the age of 6 months. Perforin gene mutations were detected in 38.8% (n = 7) of tested subjects. The novel frameshift mutation of the perforin gene (c.218_224del) was identified in four cases. Fifteen different perforin gene polymorphisms were detected in both case and control groups. Six out of nine infants with primary HLH did not survive, while the remaining three cases underwent BM transplantation. CONCLUSION: Early diagnosis of HLH is often challenging; this study should increase awareness of the prevalence of familial HLH among infants; such cases require early recognition and referral to hematopoietic stem cell transplantation.