Program Schedule

1577
In vitro polyfunctional CD4 T cell correlates of diagnostic tests for latent TB in HIV-infected subjects

Session: Poster Abstract Session: HIV: Comorbidities and Coinfections
Saturday, October 11, 2014
Room: The Pennsylvania Convention Center: IDExpo Hall BC
Posters
  • Cytokine correlates of LTBI in HIV.pdf (479.3 kB)
  • Background: Tuberculin skin test (TST) is a low cost means of determining the presence of latent tuberculosis (LTBI) in immunocompetent patients. However, few studies have examined the cytokine correlates of TB control in TST- versus TST+ subjects among HIV+ cohorts. This study examines TB-specific CD4 single cytokine and polyfunctional profiles of TST- and LTBI in HIV+ subjects.

    Methods: HIV+ adults recruited in Kampala, Uganda were differentiated into 2 groups: LTBI (>5mm response to the tuberculin skin test (TST) and negative chest x-ray; n=15), or TST- (TST <5 mm and chest x-ray; n=15). Interferon gamma release assay (IGRA) was also performed for each subject. Multicolor flow analysis was performed on PBMC stimulated with either PPD or mitogen, and frequencies of IL-2, IL-17, IFN-γ and TNF-α secreting cells were determined within the memory subset of CD4 T cells. Polyfunctionality was determined using FlowJo and SPICE software.

    Results: PPD-specific CD4+ T cell secretion of TNF-α and IFN-γ was higher in LTBI compared with TST- group (p=0.001 and p=0.002 respectively). In the IGRA+ group there was greater secretion of TNF-α compared with IGRA- though this difference was borderline (p=0.05). IL-2, IFN-γ and TNF-α all correlated with clinical response in terms size of PPD-induced induration or IGRA. Frequency of polyfunctional cells among the TST+ group was greater than and IGRA+ (p=0.04). TNF-α was the dominant cytokine in the TST+ group as 4/5 phenotypes of responding cells all generate either TNF-α alone or in combination with IFN-γ or IL-2. Both TNF-α and IL-2 were dominant among the single cytokine secretors in IGRA+ group. IFN-γ secreting cells are much more frequent in TST+ than IGRA+ subjects.

    Conclusion: CD4+ T cell cytokine responses to TB-specific antigens were significantly higher in LTBI compared to TST- HIV+ adults. While IL-2, IFN-γ and TNF-α all appear to be correlates of LTBI, TNF-α is the dominant cytokine in this regard. Perhaps measurement of TNF-α secretors to diagnostic testing for latent TB could add sensitivity but may reduce specificity. Differences exist between polyfunctional cytokine profiles of TST+ and IGRA+ HIV+ individuals which may account for difference in test performance.

    Puja Van Epps, MD1,2, Sankar Sridaran2, Htin Aung1, Michael Betts3, Zahara Toosi2 and David Canaday, MD1,2, (1)Geriatric Research Education & Clinical Center (GRECC), Louis Stokes Cleveland VA Medical Center, Cleveland, OH, (2)Infectious Diseases and HIV Medicine, Case Western Reserve University, Cleveland, OH, (3)Microbiology, University of Pennsylvania, Philadelphia, Philadelphia, PA

    Disclosures:

    P. Van Epps, None

    S. Sridaran, None

    H. Aung, None

    M. Betts, None

    Z. Toosi, None

    D. Canaday, None

    Findings in the abstracts are embargoed until 12:01 a.m. EDT, Oct. 8th with the exception of research findings presented at the IDWeek press conferences.

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