Case report: A cyclic neutropenia patient with ELANE mutation accompanied by hemophagocytic lymphohistiocytosis

Abstract

Many inborn errors of immunity may accompany secondary hemophagocytic lymphohistiocytosis (HLH), a condition typically characterized by impaired cytotoxic T and NK cell function. A considerable proportion of HLH cases also stem from chronic granulomatosis with phagocytic dysfunction. However, the development of secondary HLH in patients with severe congenital neutropenia (SCN) or cyclic neutropenia (CyN) with abnormal phagocytic cell counts has been less frequently reported. Herein, we present a case of a pediatric patient with ELANE mutation-associated CyN who developed HLH subsequent to severe bacterial, fungal, and viral infections. Notable observations included impaired NK cell degranulation function (CD107a). To the best of our knowledge, this represents the first documented instance of HLH in patients with CyN attributed to an ELANE mutation. Thus, our study establishes a link between ELANE-related CyN and HLH, underscoring the importance of considering HLH as a potential complication in these patients.

Keywords: CYN; HLH; SCN; cyclic congenital neutropenia; hemophagocytic lymphohistiocytosis.

Figure 1

Clinical course and manifestations of the patient. (A) Clinical course of the patient. (B) Chest CT shows widespread lesions in both lungs. (C, D) Neutrophils, WBC, and lymphocytes count of the patient's peripheral blood. (E) The levels of hemoglobin, platelets, and C-reactive protein (CRP) during the patient's course.

Figure 2

Imaging examination and the Next-generation sequencing of blood. (A) Next-generation sequencing of Clostridium septicum in blood. (B) Bone marrow aspirates show hemophagocytic cells that engulf neutrophils, platelets, and red blood cells. (C) The bone marrow cytology examination of the patient showed early maturation arrest of granulocytes when the neutrophil count remained low after HLH recovery.

Figure 3

Genetic diagnosis of ELANE gene mutations and Immunological Characteristics of patients. (A) Family pedigree. The patient's parents and brother both have normal phenotypes. (B) Sanger sequencing confirmed the ELANE mutation (c.709C>T, p.Gln237Ter) in the patient. (C, D) Flow cytometry detection of NK cell activity and CD107a analysis of degranulation function.