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Delayed gastrointestinal-associated lymphoid tissue reconstitution in duodenum compared with rectum in HIV-infected
Talia Sainz1, Sergio Serrano-Villar, Surinder Mann
1aDepartment of Pediatrics, La Paz University Hospital and Research Institute (ldiPAZ), Madrid bDepartment of Infectious Diseases, Ramon y Cajal University Hospital and Research Institute (IRYCIS), Faculty of Medicine, University of Alcalá, Alcalá, Spain cUniversity of California Davis Medical Center, Sacramento dCalifornia National Primate Research Center, Davis, California eUniversity of Texas Medical Branch, Galveston, Texas fSchool of Pharmacy, University of North Carolina, Chapel Hill, North Carolina gLaboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland hRush University Medical Center, Chicago, Illinois iVeterans Administration Northern California Health Care System, Mather jUniversity of California, San Francisco, San Francisco, California, USA.
Background:
We aimed to characterize the impact of antiretroviral therapy (ART) initiation on gastrointestinal-associated lymphoid tissue at various sites along the gastrointestinal site.
Methodology:
Peripheral blood and duodenal and rectal biopsies were obtained from 12 HIV to 33 treatment-naive HIV participants at baseline and after 9 months ART. Tissue was digested for immunophenotyping. Inflammatory, bacterial translocation and intestinal damage markers were measured in plasma.
Results:
Twenty-six HIV patients completed follow-up. The lowest reconstitution of CD4 T cells and the lowest CD4/CD8 ratio during ART compared with blood were observed in the duodenum with the rectum being either intermediate or approaching blood levels. Regulatory T cells were in higher proportions in the duodenum than the rectum and neither declined significantly during ART. Several correlations with biomarkers of microbial translocation were observed including increases in lipoteichoic acid levels, which reflects Gram-positive bacterial translocation, correlated with increases in %CD4 T cells in the duodenum (Rho 0.773, P = 0.033), and with decreases in duodenal regulatory T-cell populations (Rho -0.40, P = 0.045).
Conclusion:
HIV-mediated immunological disruption is greater in the duodenum than rectum and blood before and during ART. Small intestine damage may represent a unique environment for T-cell depletion, which might be attenuated by interaction with Gram-positive bacteria.
