aDepartment 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.
AIDS. 2019 Dec 1;33(15):2289-2298. doi: 10.1097/QAD.0000000000002361.
We aimed to characterize the impact of antiretroviral therapy (ART) initiation on gastrointestinal-associated lymphoid tissue at various sites along the gastrointestinal site.
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.
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).
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.
我们旨在描述抗逆转录病毒治疗（ART）启动对胃肠道各部位相关淋巴组织的影响。
从 12 名 HIV 感染者和 33 名未经治疗的 HIV 感染者中，在基线和 9 个月 ART 后分别获得外周血和十二指肠及直肠活检。对组织进行免疫表型分析。在血浆中测量炎症、细菌易位和肠道损伤标志物。
26 名 HIV 患者完成了随访。在 ART 期间，与血液相比，CD4 T 细胞重建最低，CD4/CD8 比值最低的部位是十二指肠，而直肠处于中等或接近血液水平。与直肠相比，十二指肠中的调节性 T 细胞比例更高，且在 ART 期间并未显著下降。与微生物易位的生物标志物存在多种相关性，包括反映革兰氏阳性细菌易位的脂磷壁酸水平增加，与十二指肠中 %CD4 T 细胞的增加呈正相关（Rho 0.773，P=0.033），以及与十二指肠调节性 T 细胞群的减少呈负相关（Rho -0.40，P=0.045）。
在 ART 之前和期间，HIV 介导的免疫紊乱在十二指肠中比直肠和血液更为严重。小肠损伤可能代表 T 细胞耗竭的独特环境，这种环境可能通过与革兰氏阳性细菌的相互作用而减弱。
