Evidence map›Paper›PMID 30649031›Full record

ArticleJournal of acquired immune deficiency syndromes (1999)2019

Cryptococcosis-Associated Immune Reconstitution Inflammatory Syndrome Is Associated With Dysregulation of IL-7/IL-7 Receptor Signaling Pathway in T Cells and Monocyte Activation.

Ngomu Akeem Akilimali, Daniel M Muema, Charles Specht, Christina C Chang, Mahomed-Yunus S Moosa, Stuart M Levitz, Sharon R Lewin, Martyn A French, Thumbi Ndungʼu

Open access · hybridAbstract read
In one paragraph

Article in Journal of acquired immune deficiency syndromes (1999), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.1field-weighted citation impact, top 23% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 9 citations in OpenAlex.

  1. Molecular Diagnostics ofDiseases (Basel, Switzerland) · 2024
    Review
  2. Review
  3. Review
  4. Observational
  5. Review
  6. Immune Reconstitution Disorders: Spotlight on Interferons.International journal of biomedical investigation · 2019
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 5 institutions in 5 countries.

Ngomu Akeem AkilimaliAfrica Health Research Institute (AHRI), Durban, South Africa.
Daniel M MuemaAfrica Health Research Institute (AHRI), Durban, South Africa.
Charles SpechtDivision of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, MA.
Christina C ChangAfrica Health Research Institute (AHRI), Durban, South Africa.
Mahomed-Yunus S MoosaAfrica Health Research Institute (AHRI), Durban, South Africa.
Stuart M LevitzDivision of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, MA.
Sharon R LewinThe Peter Doherty Institute for Infection and Immunity, Royal Melbourne Hospital, The University of Melbourne, Melbourne, Australia.
Martyn A FrenchMedical School and School of Biomedical Sciences, University of Western Australia, Perth, Australia.
Thumbi NdungʼuAfrica Health Research Institute (AHRI), Durban, South Africa.
Africa Health Research Institute · ZAUniversity of Massachusetts Chan Medical School · USKenya Medical Research Institute · KERoyal Perth Hospital · AUUniversity of Melbourne · AU

Funding

Howard Hughes Medical InstituteWellcome TrustWellcome Trust 107752/Z/15/Z
6 · The paper itself

Abstract

backgroundSystemic levels of interleukin (IL)-7 at antiretroviral therapy (ART) initiation have previously been shown to be predictive of HIV-linked paradoxical cryptococcosis-associated immune reconstitution inflammatory syndrome (C-IRIS). We therefore explored IL-7/IL-7 receptor (IL-7/IL-7R) signaling pathway dysfunction, with related alterations in immune function, as a mechanism underlying C-IRIS.

methodHIV-infected patients with cryptococcal meningitis who experienced C-IRIS (n = 27) were compared with CD4 T-cell count-matched counterparts without C-IRIS (n = 27), after antifungal therapy and pre-ART initiation. Flow cytometry was used to assess T-cell and monocyte phenotypes and functions.

resultsProportions of IL-7R+ CD4 or CD8 T cells correlated positively with CD4 T-cell counts and proportions of central memory and naive CD4 and CD8 T-cell pre-ART (all r > 0.50 and P < 0.05); however, the former negatively correlated with CD4 T-cell counts fold-increase on ART in non-C-IRIS but not C-IRIS patients. Higher frequencies of activated monocytes (CD14CD86 or CD14+HLA-DR+; P ≤ 0.038) were also observed in C-IRIS compared with non-C-IRIS patients, and those who failed to clear cryptococci from cerebrospinal fluid before ART had higher levels of activated monocytes (CD14+HLA-DR+, P = 0.017) compared with those who cleared. In multivariate regression, CD14+HLA-DR+ monocytes were independently associated with C-IRIS [hazard ratio = 1.055 (1.013-1.098); P = 0.009].

conclusionIn contrast to non-C-IRIS patients, C-IRIS patients displayed a lack of association between proportions of IL-7R+ T cells and several markers of T-cell homeostasis. They also exhibited higher monocyte activation linked to cerebrospinal fluid cryptococcal culture positivity before ART. These data suggest a role for IL-7/IL-7R signaling pathway dysregulation in the pathogenesis of C-IRIS, possibly linked to monocyte activation and residual pathogen burden before ART.

Indexed as

Signal TransductionAdolescentAdultAnti-HIV AgentsCase-Control StudiesCD4 Lymphocyte CountCoinfectionCryptococcosisFlow CytometryHIV InfectionsHumansImmune Reconstitution Inflammatory SyndromeInterleukin-7Lymphocyte ActivationMonocytesReceptors, Interleukin-7Anti-HIV AgentsIL7 protein, humanInterleukin-7Receptors, Interleukin-7

Identifiers

PMID30649031
PMCPMC6420066
OpenAlexW2910398092

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.