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Comparison of the integrin ?4?7 expression pattern of memory T cell subsets in HIV infection and ulcerative colitis.

ABSTRACT: Anti-?4?7 therapy with vedolizumab (VDZ) has been suggested as possible immune intervention in HIV. Relatively little is known about the ?4?7-integrin (?4?7) expression of different T-cell subsets in different anatomical compartments of healthy individuals, patients with HIV or inflammatory bowel disease (IBD). Surface expression of ?4?7 as well as the frequency of activation, homing and exhaustion markers of T cells were assessed by multicolour flow cytometry in healthy volunteers (n = 15) compared to HIV infected patients (n = 52) or patients diagnosed with ulcerative colitis (UC) (n = 14), 6 of whom treated with vedolizumab. In addition, lymph nodal cells (n = 6), gut-derived cells of healthy volunteers (n = 5) and patients with UC (n = 6) were analysed. Additionally, we studied longitudinal PBMC samples of an HIV patient who was treated with vedolizumab for concomitant UC. Overall, only minor variations of the frequency of ?4?7 on total CD4+ T cells were detectable regardless of the disease status or (VDZ) treatment status in peripheral blood and the studied tissues. Peripheral ?4?7+ CD4+ T cells of healthy individuals and patients with UC showed a higher activation status and were more frequently CCR5+ than their ?4?7- counterparts. Also, the frequency of ?4?7+ cells was significantly lower in peripheral blood CD4+ effector memory T cells of HIV-infected compared to healthy individuals and this reduced frequency did not recover in HIV patients on ART. Conversely, the frequency of peripheral blood naïve ?4?7+ CD4+ T cells was significantly reduced under VDZ treatment. The results of the current study will contribute to the understanding of the dynamics of ?4?7 expression pattern on T cells in HIV and UC and will be useful for future studies investigating VDZ as possible HIV cure strategy.

SUBMITTER: Wittner M

PROVIDER: S-EPMC6663001 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Comparison of the integrin α4β7 expression pattern of memory T cell subsets in HIV infection and ulcerative colitis.

Wittner Melanie M Schlicker Veronika V Libera Jana J Bockmann Jan-Hendrik JH Horvatits Thomas T Seiz Oliver O Kummer Silke S Manthey Carolin F CF Hüfner Anja A Kantowski Marcus M Rösch Thomas T Degen Olaf O Huber Samuel S Eberhard Johanna M JM Schulze Zur Wiesch Julian J

PloS one 20190729 7

Anti-α4β7 therapy with vedolizumab (VDZ) has been suggested as possible immune intervention in HIV. Relatively little is known about the α4β7-integrin (α4β7) expression of different T-cell subsets in different anatomical compartments of healthy individuals, patients with HIV or inflammatory bowel disease (IBD). Surface expression of α4β7 as well as the frequency of activation, homing and exhaustion markers of T cells were assessed by multicolour flow cytometry in healthy volunteers (n = 15) comp ...[more]

PMID: 31356607

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Project description:Background & aimsBetter biomarkers for prediction of ulcerative colitis (UC) development and prognostication are needed. Anti-integrin αvβ6 (anti-αvβ6) autoantibodies have been described in patients with UC. We tested for the presence of anti-αvβ6 antibodies in the preclinical phase of UC and studied their association with disease-related outcomes after diagnosis.MethodsAnti-αvβ6 autoantibodies were measured in 4 longitudinal serum samples collected from 82 subjects who later developed UC and 82 matched controls from a Department of Defense preclinical cohort (PREDICTS [Proteomic Evaluation and Discovery in an IBD Cohort of Tri-service Subjects]). In a distinct, external validation cohort (Crohn's and Colitis Canada Genetic Environmental Microbial project cohort), we tested 12 pre-UC subjects and 49 matched controls. Furthermore, anti-αvβ6 autoantibodies were measured in 2 incident UC cohorts (COMPASS [Comprehensive Care for the Recently Diagnosed IBD Patients], n = 55 and OSCCAR [Ocean State Crohn's and Colitis Area Registry], n = 104) and associations between anti-αvβ6 autoantibodies and UC-related outcomes were defined using Cox proportional hazards model.ResultsAnti-αvβ6 autoantibodies were significantly higher among individuals who developed UC compared with controls up to 10 years before diagnosis in PREDICTS. The anti-αvβ6 autoantibody seropositivity was 12.2% 10 years before diagnosis and increased to 52.4% at the time of diagnosis in subjects who developed UC compared with 2.7% in controls across the 4 time points. Anti-αvβ6 autoantibodies predicted UC development with an area under the curve of at least 0.8 up to 10 years before diagnosis. The presence of anti-αvβ6 autoantibodies in preclinical UC samples was validated in the GEM cohort. Finally, high anti-αvβ6 autoantibodies was associated with a composite of adverse UC outcomes, including hospitalization, disease extension, colectomy, systemic steroid use, and/or escalation to biologic therapy in recently diagnosed UC.ConclusionsAnti-integrin αvβ6 autoantibodies precede the clinical diagnosis of UC by up to 10 years and are associated with adverse UC-related outcomes.

Dataset Information

Comparison of the integrin ?4?7 expression pattern of memory T cell subsets in HIV infection and ulcerative colitis.

Publications

Comparison of the integrin α4β7 expression pattern of memory T cell subsets in HIV infection and ulcerative colitis.

Similar Datasets

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