Dataset Information

T Lymphocyte Subsets Associated With Prevalent Diabetes in Veterans With and Without Human Immunodeficiency Virus.

ABSTRACT:

Background

A higher proportion of circulating memory CD4+ T cells is associated with prevalent diabetes mellitus in the general population. Given the broad changes in adaptive immunity, including memory T-cell expansion, and rising prevalence of diabetes in the human immunodeficiency virus (HIV) population, we assessed whether similar relationships were present in persons with HIV (PWH).

Methods

Multiple CD4+ and CD8+ T-cell subsets were measured by flow cytometry, and prevalent diabetes cases were adjudicated by 2 physicians for PWH and HIV-negative participants in the Veterans Aging Cohort Study. Multivariable logistic regression models evaluated the association of T-cell subsets and diabetes stratified by HIV status, adjusted for cytomegalovirus serostatus and traditional risk factors.

Results

Among 2385 participants (65% PWH, 95% male, 68% African American), higher CD45RO+ memory CD4+ T cells and lower CD38+ CD4+ T cells were associated with prevalent diabetes, and had a similar effect size, in both the PWH and HIV-negative (P ≤ .05 for all). Lower CD38+CD8+ T cells were also associated with diabetes in both groups.

Conclusions

The CD4+ and CD8+ T-cell subsets associated with diabetes are similar in PWH and HIV-negative individuals, suggesting that diabetes in PWH may be related to chronic immune activation.

SUBMITTER: Bailin SS

PROVIDER: S-EPMC7323499 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Publications

T Lymphocyte Subsets Associated With Prevalent Diabetes in Veterans With and Without Human Immunodeficiency Virus.

Bailin Samuel S SS McGinnis Kathleen A KA McDonnell Wyatt J WJ So-Armah Kaku K Wellons Melissa M Tracy Russell P RP Doyle Margaret F MF Mallal Simon S Justice Amy C AC Freiberg Matthew S MS Landay Alan L AL Wanjalla Celestine C Koethe John R JR

The Journal of infectious diseases 20200601 2

<h4>Background</h4>A higher proportion of circulating memory CD4+ T cells is associated with prevalent diabetes mellitus in the general population. Given the broad changes in adaptive immunity, including memory T-cell expansion, and rising prevalence of diabetes in the human immunodeficiency virus (HIV) population, we assessed whether similar relationships were present in persons with HIV (PWH).<h4>Methods</h4>Multiple CD4+ and CD8+ T-cell subsets were measured by flow cytometry, and prevalent d ...[more]

PMID: 32052044

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Project description:BackgroundThe risk of individuals infected with human immunodeficiency virus (HIV)-1 developing tuberculosis (TB) is high, while both prognostic and diagnostic tools remain insensitive. The potential for plasma biomarkers to predict which HIV-1-infected individuals are likely to progress to active disease is unknown.MethodsThirteen analytes were measured from QuantiFERON Gold in-tube (QFT) plasma samples in 421 HIV-1-infected persons recruited within the screening and enrollment phases of a randomized, controlled trial of isoniazid preventive therapy. Blood for QFT was obtained pre-randomization. Individuals were classified into prevalent TB, incident TB, and control groups. Comparisons between groups, supervised learning methods, and weighted correlation network analyses were applied utilizing the unstimulated and background-corrected plasma analyte concentrations.ResultsUnstimulated samples showed higher analyte concentrations in the prevalent and incident TB groups compared to the control group. The largest differences were seen for C-X-C motif chemokine 10 (CXCL10), interleukin-2 (IL-2), IL-1α, transforming growth factor-α (TGF-α). A predictive model analysis using unstimulated analytes discriminated best between the control and prevalent TB groups (area under the curve [AUC] = 0.9), reasonably well between the incident and prevalent TB groups (AUC > 0.8), and poorly between the control and incident TB groups. Unstimulated IL-2 and IFN-γ were ranked at or near the top for all comparisons, except the comparison between the control vs incident TB groups. Models using background-adjusted values performed poorly.ConclusionsSingle plasma biomarkers are unlikely to distinguish between disease states in HIV-1 co-infected individuals, and combinations of biomarkers are required. The ability to detect prevalent TB is potentially important, as no blood test hitherto has been suggested as having the utility to detect prevalent TB amongst HIV-1 co-infected persons.

Project description:Background and aimsAbnormal liver enzymes (LEs) are common in those infected with human immunodeficiency virus (HIV). Histologic data on those with abnormal LE without viral hepatitis are lacking.MethodsHIV-positive subjects without hepatitis C virus, hepatitis B virus, alcohol abuse, and diabetes mellitus with more than 1 abnormal LE, defined as 1.25 ULN in aspartate aminotransferase, alanine aminotransferase, or alkaline phosphatase, over 6 months were included. Subjects underwent a 2-hour oral glucose tolerance test, fasting lipids, insulin and glucose for insulin resistance (IR) by homeostasis model assessment for insulin resistance (HOMA-IR) and dual-energy X-ray absorptiometry for fat distribution. Biopsies were read blindly to clinical data, and scored by Ishak histologic activity index for inflammation and fibrosis and NAFLD activity score.ResultsFourteen patients underwent biopsy. All were on highly active antiretroviral therapy with undetectable HIV RNA and mean CD4 614. The histologic activity index scores for inflammation and fibrosis were 3.43(1.4) and 1.71(1.26), respectively, and 2 patients had advanced fibrosis (bridging fibrosis/cirrhosis). The majority (65%) of patients had steatosis: grade 1: 21%, grade 2: 28%, and grade 3: 14%. Hepatocyte ballooning was seen in 7 (40%) but nonalcoholic steatohepatitis (NASH) was diagnosed only in 4 (26%). NAFLD activity score of all biopsies of 3.07 (2.2; range, 0 to 5). HOMA-IR was higher in those with compared with those without steatosis (3.52 vs. 1.91; P = 0.11) and highest in those with NASH (4.89). Using multivariate logistic regression, only increased γ-glutamyl transpeptidase (P = 0.0009) predicted steatosis whereas HOMA-IR (P = 0.0046) predicted NASH.ConclusionsAlthough steatosis is common in HIV patients with abnormal LE without diabetes mellitus, alcohol, or viral hepatitis coinfection, NASH was observed in only 26%. The only clinical or laboratory feature associated with biopsy proven steatosis and NASH were γ-glutamyl transpeptidase and a calculated measure of insulin resistance, respectively. Further studies are needed in this population to determine the long-term clinical significance.

Dataset Information

T Lymphocyte Subsets Associated With Prevalent Diabetes in Veterans With and Without Human Immunodeficiency Virus.

Background

Methods

Results

Conclusions

Publications

T Lymphocyte Subsets Associated With Prevalent Diabetes in Veterans With and Without Human Immunodeficiency Virus.

Similar Datasets

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