PhD Scientific Days 2022

Clinical Medicine VI. (Poster discussion will take place on the terrace of the room during the Coffee Break)

Clinical, laboratory and molecular genetic findings of patients referred with HLH

Előadó neve

Dr. Emese, Molnár

Előadó munkahelye

Department of Transfusiology, Semmelweis University School of Medicine, Budapest, Hungary

Előadó telefonszáma

+36706723652

Előadó e-mail címe

meisterwerke@gmail.com

Az előadás címe

Clinical, laboratory and molecular genetic findings of patients referred with HLH

Szerző(k) neve és munkahelye

Emese Molnár1,2,3; Andrikovics Hajnalka1, Zsuzsanna Nemes-Nagy4, Kimberly C. Gilmour2

1 Laboratory of Molecular Genetics of the Central Hospital of Southern Pest - National Institute of Hematology and Infectious Diseases, Budapest, Hungary
2 Laboratory of Immunology and Cellular Therapy, Great Ormond Street Hospital for Children, NHS Foundation Trust, London, United Kingdom.
3 Department of Transfusiology, Semmelweis University School of Medicine, Budapest, Hungary
4 Hungarian National Blood Transfusion Service, Budapest, Hungary

Bemutatás módja

Poszter

Szekció

Clinical Medicine VI. (Poster discussion will take place on the terrace of the room during the Coffee Break)

Language of the presentation

English

Preferred session

Clinical Medicine

Összefoglaló szövege

Introduction: Hemophagocytic lymphohistiocytosis (HLH) is a disorder of the immune system characterised by life-threatening inflammation. HLH may be familial HLH (FHL) or secondary, triggered by underlying conditions. FHL is the most common form of HLH with autosomal recessive inheritance, affecting 4 genes (PRF1, UNC13D, STX11, STXBP2), part of the granule release pathway of cytotoxic lymphocytes. According to the HLH-2004 protocol, from the 8 criteria that have been defined to evaluate the clinical manifestation, at least 5 criteria, an affected sibling, or a positive molecular diagnosis are required to establish HLH.
Objective: The aim of this retrospective study was to evaluate patients’laboratory and molecular genetic results and clinical presentation of patients referred with suspected HLH to the Great Ormond Street Hospital, London.
Methods: Clinical data, molecular genetic and screening test results were collected of patients with suspected HLH. The median age of the patients is 3 years (0-62) with the male to female ratio of 1:2. The found genetic variances were evaluated by SIFT, Provean and Meta SVM databases and the minor allele frequency data were collected from the NCBI database. Clinical data were evaluated by the HLH-2004 protocol. The intracellular perforin expression was screened in CD56+ Natural Killer (NK) cells by flow cytometry. The genetic variants were separated into two groups by pathogenicity described by the databases and the patients HLH severity were compared.
Results: Allele frequency in the patient population do not show significant difference compared to the MAF data. Patients with mutations described damaging had absent or suboptimal perforin expression and had higher HLH scores (average: 5,15) than patents with benign polymorphism (average:3,7, p=0,0071). However, 33% of those patients with benign variants met the clinical HLH criteria, 40% of them had 3 or 4 clinical criteria, and in three patents, no phenotype was found.
Conclusion: Primary HLH was diagnosed in 27% of the patients. Overall, 40% had an eventual clinical diagnosis of primary HLH. The frequency of pathogenic mutations was significantly higher in the examined population and these damaging mutations were predictable for clinically HLH; however, 33 % of the population where benign variants were detected also met HLH clinical criteria.
Funding: ÚNKP-21-4-I-SE-8

University and Doctoral School

Semmelweis University, Károly Rácz Doctoral School of Clinical Medicine

Supervisor

Hajnalka Andrikovics MD, PhD

Publication of my abstract

I do not give consent to the publication of my abstract on the website of the congress.

Kind

Szabad

Status

elfogadva

Accepted presentation method

poszter

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

2847

Start

11:15

End

11:20

Authors (legacy)

Emese Molnár1,2,3; Andrikovics Hajnalka1, Zsuzsanna Nemes-Nagy4, Kimberly C. Gilmour2

1 Laboratory of Molecular Genetics of the Central Hospital of Southern Pest - National Institute of Hematology and Infectious Diseases, Budapest, Hungary
2 Laboratory of Immunology and Cellular Therapy, Great Ormond Street Hospital for Children, NHS Foundation Trust, London, United Kingdom.
3 Department of Transfusiology, Semmelweis University School of Medicine, Budapest, Hungary
4 Hungarian National Blood Transfusion Service, Budapest, Hungary