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Molecular genetics of primary hemophagocytic lymphohistiocytosis among Polish patients
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  • Katarzyna Bąbol-Pokora,
  • Magdalena Wołowiec,
  • Katarzyna Popko,
  • Aleksandra Jasinska,
  • Yenan Bryceson,
  • Bianca Tesi,
  • Jan-Inge Henter,
  • Wojciech Mlynarski,
  • Iwona Malinowska
Katarzyna Bąbol-Pokora
Medical University of Lodz
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Magdalena Wołowiec
Medical University of Warsaw
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Katarzyna Popko
Medical University of Warsaw
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Aleksandra Jasinska
Medical University of Lodz
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Yenan Bryceson
Karolinska Institute
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Bianca Tesi
Karolinska Institutet
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Jan-Inge Henter
Childhood Cancer Research Unit, Department of Woman and Child Health, Karolinska Institutet, Karolinska University Hospital
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Wojciech Mlynarski
Medical University of Lodz
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Iwona Malinowska
Clinic of Pediatric Hematology and Oncology

Corresponding Author:[email protected]

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Abstract

Background Hemophagocytic lymphohistiocytosis (HLH) is a clinical syndrome of life-threatening inflammation caused by an excessive, prolonged, and ineffective immune response. An increasing number of HLH cases is recognized in Poland but the genetic causes of familial HLH (FHL) have not been reported. We investigated the molecular genetics and associated outcomes of Polish pediatric patients who met HLH criteria. Methods We studied 54 patients with HLH, 36 of whom qualified for genetic studies. Twenty-five patients were subjected to direct sequencing of the PRF1, UNC13D, STX11, XIAP and SH2D1A genes. Additionally, 11 patients were subjected to targeted next generation sequencing. In our study group, Results 17 patients (31%) were diagnosed with primary HLH, with biallelic FHL variants identified in 13 (36%) patients whereas hemizygous changes were identified in 4 patients with X-linked lymphoproliferative diseases (XLP). In addition, one patient was diagnosed with X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection and neoplasia (XMEN) due to a hemizygous MAGT1 variant and another newborn with autoinflammatory syndrome caused by MVK variants. The majority (65%) of FHL patients carried UNC13D pathogenic variants, whereas PRF1 variants only explained two patients. Among 35 secondary HLH patients, EBV was the most common trigger noted in 23 (65%) of the patients. In three patients with secondary HLH, heterozygous variants of FHL genes were found. Conclusions Overall survival for the entire study group was 74% with median of 3,6 years of follow-up. Our results highlight the molecular causes of primary HLH in Poland.