PhD Scientific Days 2019

Budapest, April 25–26, 2019

Clinical and molecular diagnosis in 45 patients referred with HLH

Molnár, Emese

Great Ormond Street Hospital for Children NHS Foundation Trust; Hungarian National Blood Transfusion Service; Central Hospital of Southern Pest, National Institute of Hematology and Infectious Diseases
Laboratory of Molecular Genetics;

Language of the presentation

English

Text of the abstract

Introduction:
Familial hemophagocytic lymphohistiocytosis (FLH) is a severe disorder of the immune system characterised by life-threatening inflammation with autosomal recessive inheritance four genes including perforin.

Objective:
The aim of this retrospective study was to evaluate patients’ perforin expression, molecular
genetic results and clinical presentation in 45 HLH patients.

Methods:
Clinical data from 45 patients with the clinical suspicion of FHL (median age: 3 years (range: 0-62 years; male to female ratio 1:2) was evaluated and correlated with perforin expression, and with genetic variants in the perforin gene (PRF1). The severity of FHL symptoms was graded by the HLH-2004 protocol. Intracellular perforin expression in CD56+ Natural Killer (NK) cells were screened by flow cytometry.

Results:
The frequencies of benign variants in the patient population do not show a significant difference compared to the MAF data (p=non-significant). Patients with damaging PRF1 gene mutations had absent (5 patients) or abnormal (3 patients) perforin expression and met more HLH criteria than patients with benign polymorphism (average: 5.15 versus 3,71, p=0,0071) However, 33% of those patients where benign variants were identified met clinical HLH criteria and had abnormal perforin expression;40% of them had 3 or 4 clinical criteria; in three patients, no HLH phenotype was found, and they had abnormal expression.

Conclusion:
The frequency of pathogenic mutations with absent/abnormal expression was significantly higher in this population and was predictable for clinical HLH; however, 33 % of patients without pathogenic PRF1 mutation (only with benign PRF1 variants) also met FHL clinical criteria, and 70 % of them had abnormal perforin expression.

Data of the presenter

Doctoral School: Clinical Medicine
Program: Clinical Haematology (06)
Supervisor: Dr. Andrikovics Hajnalka
E-mail address: andrikovics.hajnalka@dpckorhaz.hu