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Case report: Hemophagocytic lymphohistiocytosis in a child with primary immunodeficiency infected with Talaromyces marneffei

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening immune-mediated disease that affects patients with known genetic defects and is increasingly found among those with autoimmune diseases and persistent infections. Talaromyces marneffei (TM) is a human opportunistic fungus that commonly i...

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Autores principales: Yan, Huimin, Mo, Yunjun, Liu, Shilin, Luo, Xiaojuan, Liu, Lianlian, Zhou, Lintao, Zhang, Xiuming, Chen, Yunsheng, Cao, Ke
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9755863/
https://www.ncbi.nlm.nih.gov/pubmed/36532052
http://dx.doi.org/10.3389/fimmu.2022.1038354
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author Yan, Huimin
Mo, Yunjun
Liu, Shilin
Luo, Xiaojuan
Liu, Lianlian
Zhou, Lintao
Zhang, Xiuming
Chen, Yunsheng
Cao, Ke
author_facet Yan, Huimin
Mo, Yunjun
Liu, Shilin
Luo, Xiaojuan
Liu, Lianlian
Zhou, Lintao
Zhang, Xiuming
Chen, Yunsheng
Cao, Ke
author_sort Yan, Huimin
collection PubMed
description Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening immune-mediated disease that affects patients with known genetic defects and is increasingly found among those with autoimmune diseases and persistent infections. Talaromyces marneffei (TM) is a human opportunistic fungus that commonly infects immunodeficient or immunosuppressed individuals. Few TM-associated secondary HLH cases resulting from autoimmune deficiency have been reported previously. The current case study describes a pediatric patient hospitalized with recurrent fever and lymphadenopathy. The child had abnormal blood cell classification, and microscopy revealed mature granulocytes that phagocytized fungal spores. It was speculated that the patient was infected with TM. The pathogen was detected earlier than the blood culture and confirmed by metagenomic next-generation sequencing. Whole-exome sequencing revealed that the patient had complex mutations associated with immunodeficiency. This included a mutation in exon 3 of the CD40LG gene, c.346G>A, which may be linked to hyper-IgM syndrome, a primary immunodeficiency disease with immunoglobulin conversion recombination defects that could explain the patient’s increased susceptibility to serious opportunistic infections. In addition, a heterozygous frameshift variant, c.820dup (p.Asp274GlyfsTer61), was detected in exon 6 of CARD9, a key gene associated with fungal immune surveillance. After 4 days of fungal treatment, the abnormal blood cell clusters disappeared, but other infections occurred in succession for 6 months after rehabilitation. The patient was followed with the aim of providing subsequent immunotherapy. This study found that infection can trigger HLH in HIV-negative individuals, highlighting the importance of early definitive identification of the causative agent and investigation of potential immunodeficiency.
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spelling pubmed-97558632022-12-17 Case report: Hemophagocytic lymphohistiocytosis in a child with primary immunodeficiency infected with Talaromyces marneffei Yan, Huimin Mo, Yunjun Liu, Shilin Luo, Xiaojuan Liu, Lianlian Zhou, Lintao Zhang, Xiuming Chen, Yunsheng Cao, Ke Front Immunol Immunology Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening immune-mediated disease that affects patients with known genetic defects and is increasingly found among those with autoimmune diseases and persistent infections. Talaromyces marneffei (TM) is a human opportunistic fungus that commonly infects immunodeficient or immunosuppressed individuals. Few TM-associated secondary HLH cases resulting from autoimmune deficiency have been reported previously. The current case study describes a pediatric patient hospitalized with recurrent fever and lymphadenopathy. The child had abnormal blood cell classification, and microscopy revealed mature granulocytes that phagocytized fungal spores. It was speculated that the patient was infected with TM. The pathogen was detected earlier than the blood culture and confirmed by metagenomic next-generation sequencing. Whole-exome sequencing revealed that the patient had complex mutations associated with immunodeficiency. This included a mutation in exon 3 of the CD40LG gene, c.346G>A, which may be linked to hyper-IgM syndrome, a primary immunodeficiency disease with immunoglobulin conversion recombination defects that could explain the patient’s increased susceptibility to serious opportunistic infections. In addition, a heterozygous frameshift variant, c.820dup (p.Asp274GlyfsTer61), was detected in exon 6 of CARD9, a key gene associated with fungal immune surveillance. After 4 days of fungal treatment, the abnormal blood cell clusters disappeared, but other infections occurred in succession for 6 months after rehabilitation. The patient was followed with the aim of providing subsequent immunotherapy. This study found that infection can trigger HLH in HIV-negative individuals, highlighting the importance of early definitive identification of the causative agent and investigation of potential immunodeficiency. Frontiers Media S.A. 2022-12-02 /pmc/articles/PMC9755863/ /pubmed/36532052 http://dx.doi.org/10.3389/fimmu.2022.1038354 Text en Copyright © 2022 Yan, Mo, Liu, Luo, Liu, Zhou, Zhang, Chen and Cao https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Yan, Huimin
Mo, Yunjun
Liu, Shilin
Luo, Xiaojuan
Liu, Lianlian
Zhou, Lintao
Zhang, Xiuming
Chen, Yunsheng
Cao, Ke
Case report: Hemophagocytic lymphohistiocytosis in a child with primary immunodeficiency infected with Talaromyces marneffei
title Case report: Hemophagocytic lymphohistiocytosis in a child with primary immunodeficiency infected with Talaromyces marneffei
title_full Case report: Hemophagocytic lymphohistiocytosis in a child with primary immunodeficiency infected with Talaromyces marneffei
title_fullStr Case report: Hemophagocytic lymphohistiocytosis in a child with primary immunodeficiency infected with Talaromyces marneffei
title_full_unstemmed Case report: Hemophagocytic lymphohistiocytosis in a child with primary immunodeficiency infected with Talaromyces marneffei
title_short Case report: Hemophagocytic lymphohistiocytosis in a child with primary immunodeficiency infected with Talaromyces marneffei
title_sort case report: hemophagocytic lymphohistiocytosis in a child with primary immunodeficiency infected with talaromyces marneffei
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9755863/
https://www.ncbi.nlm.nih.gov/pubmed/36532052
http://dx.doi.org/10.3389/fimmu.2022.1038354
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