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Analysis of genes involved in immune response in children with HLH – case series

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Gowin, Ewelina, Szaflarski, Witold, Januszkiewicz-Lewandowska, Danuta·2025·Pediatric Rheumatology
DOI 10.1186/s12969-025-01169-1PMC PMC12639710

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Abstract

Background Hemophagocytic lymphohistiocytosis (HLH) is an excessive immune activation syndrome. The genetic studies on every patient diagnosed with HLH recently became a standard of care. The likelihood of identifying a gene mutation is highest in the youngest patients. Results [Four HLH patients had changes in the following five genes](mailto:peter.fritsch@medunigraz.at): [NLRP1 (c.923G>A)](mailto:peter.fritsch@medunigraz.at), [DOCK 8 (Dedicator of Cytokinesis 8) (c.3067A>G)](mailto:peter.fritsch@medunigraz.at), [AIRE gene (c.10G>A) and one in the RNASEH2B (c.649T>C)](mailto:peter.fritsch@medunigraz.at), [PSTPIP1 (c.1213C>T)](mailto:peter.fritsch@medunigraz.at). No mutations in genes previously associated with HLH syndrome were found. Conclusions [The described cases show that genetic analysis is helpful for the diagnosis of HLH in pediatric patients. The functional analysis of a putative mutation is essential for understanding the pathological mechanism; while not every change in DNA might be responsible for the disease. Each patient might have different mutations; however, they all develop the same clinical outcome. Disruption at different levels can result in a similar picture.](mailto:peter.fritsch@medunigraz.at)

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Fig. 1 In silico molecular analysis of the detected changes (A) The location of the Arg308Gln change in the AlphaFold-predicted model of NLRP1 protein. Chimera X-based fitting of two models containing either arginine or glutamine. (B) The location of the Ile1023Val change in the AlphaFold-predicted model of DOCK8 protein. Structures of two AlphaFold-predicted models containing either arginine or glutamine in the position 2023 of DOCK8 protein. (C) The location of the Asp4Asn change in the AlphaFold-predicted model of aire protein. Structures of two AlphaFold-predicted models containing either aspartic acid or asparagine in the position 4 of aire protein. (D) The location of serine 217 in the AlphaFold-predicted model of rnase H 2B protein. Locations of amino acid residues associated with Aicardi-Goutiéres syndrome (AGS) and the location of serine 217. (E) The location of the Arg405Cys change in the AlphaFold-predicted model of PSTPIP1 protein. Structures of two AlphaFold-predicted models containing either arginine or cysteine in the position 405 of PSTPIP1 protein as well as a chimera X-based fitting structure of two models containing either arginine or cysteine
Fig. 1 In silico molecular analysis of the detected changes (A) The location of the Arg308Gln change in the AlphaFold-predicted model of NLRP1 protein. Chimera X-based fitting of two models containing either arginine or glutamine. (B) The location of the Ile1023Val change in the AlphaFold-predicted model of DOCK8 protein. Structures of two AlphaFold-predicted models containing either arginine or glutamine in the position 2023 of DOCK8 protein. (C) The location of the Asp4Asn change in the AlphaFold-predicted model of aire protein. Structures of two AlphaFold-predicted models containing either aspartic acid or asparagine in the position 4 of aire protein. (D) The location of serine 217 in the AlphaFold-predicted model of rnase H 2B protein. Locations of amino acid residues associated with Aicardi-Goutiéres syndrome (AGS) and the location of serine 217. (E) The location of the Arg405Cys change in the AlphaFold-predicted model of PSTPIP1 protein. Structures of two AlphaFold-predicted models containing either arginine or cysteine in the position 405 of PSTPIP1 protein as well as a chimera X-based fitting structure of two models containing either arginine or cysteineCC BY-NC-ND · PubMed Central

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Citations

Cites

Research works printed but not linked: 17

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Metadata

Authors
Gowin, E., Szaflarski, W., & Januszkiewicz-Lewandowska, D.
Affiliations
Poznan University of Medical Sciences (PL)
Corresponding author
Gowin, Ewelina
ORCID
Venue
Pediatric Rheumatology
Publisher
Springer Science and Business Media LLC
Published
2025-11-21
Volume
23
Issue
1
Pages
119-119
ISSN
1546-0096 (ISSN-L)
DOI
10.1186/s12969-025-01169-1
PMC
PMC12639710
OpenAlex
W4416504390
Cited by
0
References
2
FWCI
0.00
Type
journal article
Language
en
Open access
Licence
Locations
  • Pediatric Rheumatology (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Health Sciences › Medicine › Hematology › Autoimmune and Inflammatory Disorders Research
  • Life Sciences › Immunology and Microbiology › Immunology › Immunodeficiency and Autoimmune Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
Keywords
hemophagocytic lymphohistiocytosis, pediatric HLH, genetic mutations, NLRP1, DOCK8, AIRE, RNASEH2B, PSTPIP1, immune response genes, genetic diagnosis, functional analysis of mutations
MeSH terms
NLR Proteins, AIRE Protein, Child, Child, Preschool, Cytoskeletal Proteins, Female, Humans, Infant, Male, Mutation, Transcription Factors, Guanine Nucleotide Exchange Factors, Adaptor Proteins, Signal Transducing, Lymphohistiocytosis, Hemophagocytic

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