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Article: Application of Flow Cytometry in the Diagnostics Pipeline of Primary Immunodeficiencies Underlying Disseminated Talaromyces marneffei Infection in HIV-Negative Children

TitleApplication of Flow Cytometry in the Diagnostics Pipeline of Primary Immunodeficiencies Underlying Disseminated Talaromyces marneffei Infection in HIV-Negative Children
Authors
KeywordsTaloromyces marneffei
flow cytometry
X-linked hyper-IgM syndrome
CD40L
STAT1
Issue Date2019
PublisherFrontiers Research Foundation. The Journal's web site is located at http://www.frontiersin.org/immunology
Citation
Frontiers in Immunology, 2019, v. 10, p. article no. 2189 How to Cite?
AbstractTalaromyces (Penicillium) marneffei is an AIDS-defining infection in Southeast Asia and is associated with high mortality. It is rare in non-immunosuppressed individuals, especially children. Little is known about host immune response and genetic susceptibility to this endemic fungus. Genetic defects in the interferon-gamma (IFN-γ)/STAT1 signaling pathway, CD40/CD40 ligand- and IL12/IL12-receptor-mediated crosstalk between phagocytes and T-cells, and STAT3-mediated Th17 differentiation have been reported in HIV-negative children with talaromycosis and other endemic mycoses such as histoplasmosis, coccidioidomycosis, and paracoccidioidomycosis. There is a need to design a diagnostic algorithm to evaluate such patients. In this article, we review a cohort of pediatric patients with disseminated talaromycosis referred to the Asian Primary Immunodeficiency Network for genetic diagnosis of PID. Using these illustrative cases, we propose a diagnostics pipeline that begins with immunoglobulin pattern (IgG, IgA, IgM, and IgE) and enumeration of lymphocyte subpopulations (T-, B-, and NK-cells). The former could provide clues for hyper-IgM syndrome and hyper-IgE syndrome. Flow cytometric evaluation of CD40L expression should be performed for patients suspected to have X-linked hyper-IgM syndrome. Defects in interferon-mediated JAK-STAT signaling are evaluated by STAT1 phosphorylation studies by flow cytometry. STAT1 hyperphosphorylation in response to IFN-α or IFN-γ and delayed dephosphorylation is diagnostic for gain-of-function STAT1 disorder, while absent STAT1 phosphorylation in response to IFN-γ but normal response to IFN-α is suggestive of IFN-γ receptor deficiency. This simple and rapid diagnostic algorithm will be useful in guiding genetic studies for patients with disseminated talaromycosis requiring immunological investigations.
Persistent Identifierhttp://hdl.handle.net/10722/289148
ISSN
2019 Impact Factor: 5.085
2015 SCImago Journal Rankings: 2.810
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLee, PP-
dc.contributor.authorLao-araya, M-
dc.contributor.authorYang, J-
dc.contributor.authorChan, KW-
dc.contributor.authorMA, H-
dc.contributor.authorPEI, LC-
dc.contributor.authorKUI, L-
dc.contributor.authorMao, H-
dc.contributor.authorYang, W-
dc.contributor.authorZhao, X-
dc.contributor.authorTrakultivakorn, M-
dc.contributor.authorLau, YL-
dc.date.accessioned2020-10-22T08:08:30Z-
dc.date.available2020-10-22T08:08:30Z-
dc.date.issued2019-
dc.identifier.citationFrontiers in Immunology, 2019, v. 10, p. article no. 2189-
dc.identifier.issn1664-3224-
dc.identifier.urihttp://hdl.handle.net/10722/289148-
dc.description.abstractTalaromyces (Penicillium) marneffei is an AIDS-defining infection in Southeast Asia and is associated with high mortality. It is rare in non-immunosuppressed individuals, especially children. Little is known about host immune response and genetic susceptibility to this endemic fungus. Genetic defects in the interferon-gamma (IFN-γ)/STAT1 signaling pathway, CD40/CD40 ligand- and IL12/IL12-receptor-mediated crosstalk between phagocytes and T-cells, and STAT3-mediated Th17 differentiation have been reported in HIV-negative children with talaromycosis and other endemic mycoses such as histoplasmosis, coccidioidomycosis, and paracoccidioidomycosis. There is a need to design a diagnostic algorithm to evaluate such patients. In this article, we review a cohort of pediatric patients with disseminated talaromycosis referred to the Asian Primary Immunodeficiency Network for genetic diagnosis of PID. Using these illustrative cases, we propose a diagnostics pipeline that begins with immunoglobulin pattern (IgG, IgA, IgM, and IgE) and enumeration of lymphocyte subpopulations (T-, B-, and NK-cells). The former could provide clues for hyper-IgM syndrome and hyper-IgE syndrome. Flow cytometric evaluation of CD40L expression should be performed for patients suspected to have X-linked hyper-IgM syndrome. Defects in interferon-mediated JAK-STAT signaling are evaluated by STAT1 phosphorylation studies by flow cytometry. STAT1 hyperphosphorylation in response to IFN-α or IFN-γ and delayed dephosphorylation is diagnostic for gain-of-function STAT1 disorder, while absent STAT1 phosphorylation in response to IFN-γ but normal response to IFN-α is suggestive of IFN-γ receptor deficiency. This simple and rapid diagnostic algorithm will be useful in guiding genetic studies for patients with disseminated talaromycosis requiring immunological investigations.-
dc.languageeng-
dc.publisherFrontiers Research Foundation. The Journal's web site is located at http://www.frontiersin.org/immunology -
dc.relation.ispartofFrontiers in Immunology-
dc.rightsThis Document is Protected by copyright and was first published by Frontiers. All rights reserved. It is reproduced with permission.-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectTaloromyces marneffei-
dc.subjectflow cytometry-
dc.subjectX-linked hyper-IgM syndrome-
dc.subjectCD40L-
dc.subjectSTAT1-
dc.titleApplication of Flow Cytometry in the Diagnostics Pipeline of Primary Immunodeficiencies Underlying Disseminated Talaromyces marneffei Infection in HIV-Negative Children-
dc.typeArticle-
dc.identifier.emailLee, PP: ppwlee@hku.hk-
dc.identifier.emailYang, J: jingy09@hku.hk-
dc.identifier.emailChan, KW: kwchan@hku.hk-
dc.identifier.emailYang, W: yangwl@hku.hk-
dc.identifier.emailLau, YL: lauylung@hku.hk-
dc.identifier.authorityLee, PP=rp00462-
dc.identifier.authorityYang, W=rp00524-
dc.identifier.authorityLau, YL=rp00361-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.3389/fimmu.2019.02189-
dc.identifier.pmid31572394-
dc.identifier.pmcidPMC6753679-
dc.identifier.scopuseid_2-s2.0-85072767085-
dc.identifier.hkuros316122-
dc.identifier.volume10-
dc.identifier.spagearticle no. 2189-
dc.identifier.epagearticle no. 2189-
dc.identifier.isiWOS:000485333600001-
dc.publisher.placeSwitzerland-
dc.identifier.issnl1664-3224-

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