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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
Title | Application of Flow Cytometry in the Diagnostics Pipeline of Primary Immunodeficiencies Underlying Disseminated Talaromyces marneffei Infection in HIV-Negative Children |
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Authors | |
Keywords | Taloromyces marneffei flow cytometry X-linked hyper-IgM syndrome CD40L STAT1 |
Issue Date | 2019 |
Publisher | Frontiers 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? |
Abstract | Talaromyces (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 Identifier | http://hdl.handle.net/10722/289148 |
ISSN | 2023 Impact Factor: 5.7 2023 SCImago Journal Rankings: 1.868 |
PubMed Central ID | |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Lee, PP | - |
dc.contributor.author | Lao-araya, M | - |
dc.contributor.author | Yang, J | - |
dc.contributor.author | Chan, KW | - |
dc.contributor.author | MA, H | - |
dc.contributor.author | PEI, LC | - |
dc.contributor.author | KUI, L | - |
dc.contributor.author | Mao, H | - |
dc.contributor.author | Yang, W | - |
dc.contributor.author | Zhao, X | - |
dc.contributor.author | Trakultivakorn, M | - |
dc.contributor.author | Lau, YL | - |
dc.date.accessioned | 2020-10-22T08:08:30Z | - |
dc.date.available | 2020-10-22T08:08:30Z | - |
dc.date.issued | 2019 | - |
dc.identifier.citation | Frontiers in Immunology, 2019, v. 10, p. article no. 2189 | - |
dc.identifier.issn | 1664-3224 | - |
dc.identifier.uri | http://hdl.handle.net/10722/289148 | - |
dc.description.abstract | Talaromyces (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.language | eng | - |
dc.publisher | Frontiers Research Foundation. The Journal's web site is located at http://www.frontiersin.org/immunology | - |
dc.relation.ispartof | Frontiers in Immunology | - |
dc.rights | This Document is Protected by copyright and was first published by Frontiers. All rights reserved. It is reproduced with permission. | - |
dc.rights | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. | - |
dc.subject | Taloromyces marneffei | - |
dc.subject | flow cytometry | - |
dc.subject | X-linked hyper-IgM syndrome | - |
dc.subject | CD40L | - |
dc.subject | STAT1 | - |
dc.title | Application of Flow Cytometry in the Diagnostics Pipeline of Primary Immunodeficiencies Underlying Disseminated Talaromyces marneffei Infection in HIV-Negative Children | - |
dc.type | Article | - |
dc.identifier.email | Lee, PP: ppwlee@hku.hk | - |
dc.identifier.email | Yang, J: jingy09@hku.hk | - |
dc.identifier.email | Chan, KW: kwchan@hku.hk | - |
dc.identifier.email | Yang, W: yangwl@hku.hk | - |
dc.identifier.email | Lau, YL: lauylung@hku.hk | - |
dc.identifier.authority | Lee, PP=rp00462 | - |
dc.identifier.authority | Yang, W=rp00524 | - |
dc.identifier.authority | Lau, YL=rp00361 | - |
dc.description.nature | published_or_final_version | - |
dc.identifier.doi | 10.3389/fimmu.2019.02189 | - |
dc.identifier.pmid | 31572394 | - |
dc.identifier.pmcid | PMC6753679 | - |
dc.identifier.scopus | eid_2-s2.0-85072767085 | - |
dc.identifier.hkuros | 316122 | - |
dc.identifier.volume | 10 | - |
dc.identifier.spage | article no. 2189 | - |
dc.identifier.epage | article no. 2189 | - |
dc.identifier.isi | WOS:000485333600001 | - |
dc.publisher.place | Switzerland | - |
dc.identifier.issnl | 1664-3224 | - |