Evidence map›Paper›PMID 26611774›Full record

ArticleClinical infectious diseases : an official publication of the Infectious Diseases Society of America2016

Robust Reconstitution of Tuberculosis-Specific Polyfunctional CD4+ T-Cell Responses and Rising Systemic Interleukin 6 in Paradoxical Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome.

Shruthi Ravimohan, Neo Tamuhla, Kebatshabile Nfanyana, Andrew P Steenhoff, Rona Letlhogile, Ian Frank, Rob Roy MacGregor, Robert Gross, Drew Weissman, Gregory P Bisson

Open access · bronzeAbstract read
In one paragraph

Article in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
4.1field-weighted citation impact, top 6% 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

24 citing papers in PubMed, 41 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. The use of TNF-α antagonists in tuberculosis to control severe paradoxical reaction or immune reconstitution inflammatory syndrome: a case series and literature review.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2023
    Review
  5. Review
  6. Phenotypic Profile ofOpen forum infectious diseases · 2023
    Article
  7. Review
  8. Article
  9. Observational
  10. Review
  11. Lung Injury on Antiretroviral Therapy in Adults With Human Immunodeficiency Virus/Tuberculosis.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2020
    Article
  12. Article
  13. Observational
  14. Observational
  15. High Activation of γδ T Cells and the γδ2Frontiers in immunology · 2019
    Article
  16. Article
  17. Common Variation inOpen forum infectious diseases · 2018
    Article
  18. Immune Reconstitution Inflammatory Syndrome in HIV-Infected Immigrants.The American journal of tropical medicine and hygiene · 2017
    Article
  19. Article
  20. 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

10 authors at 3 institutions in 2 countries.

Shruthi RavimohanDepartment of Medicine, Division of Infectious Diseases, Perelman School of Medicine at the University of Pennsylvania, Philadelphia.
Neo TamuhlaBotswana-UPenn Partnership, Gaborone.
Kebatshabile NfanyanaBotswana-UPenn Partnership, Gaborone.
Andrew P SteenhoffBotswana-UPenn Partnership, Gaborone.
Rona LetlhogileBotswana-UPenn Partnership, Gaborone.
Ian FrankDepartment of Medicine, Division of Infectious Diseases, Perelman School of Medicine at the University of Pennsylvania, Philadelphia.
Rob Roy MacGregorDepartment of Medicine, Division of Infectious Diseases, Perelman School of Medicine at the University of Pennsylvania, Philadelphia.
Robert GrossDepartment of Medicine, Division of Infectious Diseases, Perelman School of Medicine at the University of Pennsylvania, Philadelphia.
Drew WeissmanDepartment of Medicine, Division of Infectious Diseases, Perelman School of Medicine at the University of Pennsylvania, Philadelphia.
Gregory P BissonDepartment of Medicine, Division of Infectious Diseases, Perelman School of Medicine at the University of Pennsylvania, Philadelphia.
Botswana Open University · BWUniversity of Pennsylvania · USChildren's Hospital of Philadelphia · US

Funding

Virus & Reservoirs CoreP30AI045008 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI ROBERT GROSS · 1999 to 2026
$78.6M
Immunology and Outcomes after HAART in HIV/TB CoinfectionR01AI080337 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI BISSON, GREGORY P. · 2009 to 2013
$3.5M
NIAID NIH HHS AI045008NIAID NIH HHS P30 AI045008NIAID NIH HHS R01 AI080337NIAID NIH HHS R01AI080337
6 · The paper itself

Abstract

backgroundThe immunopathogenesis of paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) remains unclear. We determined the association between pathogen-specific T-cell responses and development of paradoxical TB-IRIS on antiretroviral therapy (ART).

methodsThis study was nested within a prospective cohort study of HIV-infected patients with active pulmonary tuberculosis and baseline CD4 counts ≤125 cells/µL initiating ART. T-cell immune activation (CD38, HLA-DR, and PD-1 expression), phenotype, and polyfunctional pathogen-specific cellular immune responses prior to and 4 weeks after ART initiation were determined by flow cytometry. Patients with TB-IRIS were compared to non-IRIS controls using χ(2) and rank-sum tests and logistic regression.

resultsTB-IRIS patients and controls had similar CD4 counts, levels of T-cell-associated immune activation, frequencies of T-cell memory subsets, and frequencies of interferon gamma (IFN-γ(+))/interleukin 2 (IL-2(+))/tumor necrosis factor alpha (TNF-α(+)) CD4(+) T-cells prior to ART initiation. After ART initiation, cellular immune activation and T-cell subsets also were similar in TB-IRIS patients and controls. In contrast, TB-IRIS patients had significantly greater early increases in the frequency of tuberculosis-specific polyfunctional IFN-γ(+)/IL-2(+)/TNF-α(+) CD4(+) T-cells on ART (P = .02); each quartile increase in the percentage of these cells was independently associated with a 2.8-fold increased risk of TB-IRIS (95% confidence interval, 1.1 to 7.5-fold). In a secondary analysis, patients with TB-IRIS had rapid, concomitant increases in tuberculosis-specific adaptive immune responses and interleukin 6 (IL-6) levels, whereas controls with similarly rapid increases in cellular immune function had IL-6 levels that tended to decrease on ART.

conclusionsRapid expansion of tuberculosis-specific polyfunctional CD4(+) T-cell responses, likely linked to increases in IL-6, is associated with development of paradoxical TB-IRIS.

Indexed as

AdultAgedAnti-HIV AgentsAntiretroviral Therapy, Highly ActiveBotswanaCD4 Lymphocyte CountCD4-Positive T-LymphocytesCoinfectionFemaleFlow CytometryHIV InfectionsHumansImmune Reconstitution Inflammatory SyndromeImmunity, CellularInterleukin-6Lymphocyte ActivationAnti-HIV AgentsIL6 protein, humanInterleukin-6ARTcellular immune functionHIVimmune reconstitution inflammatory syndrome (IRIS)tuberculosis

Identifiers

PMID26611774
PMCPMC4772844
OpenAlexW2314234170

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.