Discordance Between Peripheral and Colonic Markers of Inflammation During Suppressive ART

Dunham, Richard M. PhD*; Vujkovic-Cvijin, Ivan†,‡; Yukl, Steven A. MD§; Broadhurst, Mara J. PhD†,‡; Loke, P'ng PhD; Albright, Rebecca G.; Wong, Joseph K. MD§; Lederman, Michael M. MD; Somsouk, Ma MD; Hunt, Peter W. MD#; Martin, Jeffrey N. MD, MPH#; Deeks, Steven G. MD#; McCune, Joseph M. MD, PhD

JAIDS Journal of Acquired Immune Deficiency Syndromes: 1 February 2014 - Volume 65 - Issue 2 - p 133–141
doi: 10.1097/01.qai.0000437172.08127.0b
Basic and Translational Science

Objective: Persistent systemic inflammation is associated with the inability of some HIV-infected patients to normalize circulating CD4+ T-cell levels after years of suppressive antiretroviral therapy. In this study, we sought to understand whether such systemic inflammation is also associated with detectable signs of inflammation in biopsies from the rectosigmoid colon.

Design: Immunologic and virological parameters were studied in the peripheral blood and in rectosigmoid colon biopsies from individuals with viral suppression for at least 2 years and with peripheral CD4+ T-cell levels of <350 cells per cubic millimeter (immunologic nonresponders, n = 18) or >500 cells per cubic millimeter (immunologic responders, n = 16).

Methods: Peripheral blood and rectosigmoid colon biopsies were analyzed by flow cytometry, enzyme-linked immunosorbent assay, and quantitative polymerase chain reaction.

Results: Nonresponders had elevated T-cell activation and inflammatory cytokines in the circulation, but inflammatory gene expression in colon biopsies was not different as compared with responders, and there was little relationship between blood and colon markers of inflammation. Blood inflammatory markers were positively associated with soluble CD14 levels indicative of monocyte activation.

Conclusions: These findings demonstrate that, in the context of treated HIV disease, it is easier to detect parameters of inflammation (including blood monocyte activation) in the peripheral blood than in isolated rectosigmoid colon biopsies. Accordingly, interventions to block such inflammation in this population might be most conveniently and accurately assessed in blood.

*HIV Discovery Performance Unit, GlaxoSmithKline, Research Triangle Park, NC;

Division of Experimental Medicine, Department of Medicine, University of California, San Francisco, San Francisco, CA (P'ng Loke is now with the Department of Microbiology, Division of Parasitology, New York University Medical Center, New York, NY);

Biomedical Sciences Graduate Program, University of California, San Francisco, San Francisco, CA;

§Division of Infectious Diseases, Department of Medicine, University of California, San Francisco and San Francisco VA Medical Center, San Francisco, CA;

Division of Infectious Diseases and HIV Medicine, Department of Medicine, Case Western Reserve University, Cleveland, OH;

Division of Gastroenterology, Department of Medicine, University of California, San Francisco, San Francisco, CA; and

#Positive Health Program, Department of Medicine, San Francisco General Hospital, University of California, San Francisco, San Francisco, CA.

Correspondence to: Joseph M. McCune, Division of Experimental Medicine, Department of Medicine, University of California, San Francisco (UCSF) Box 1234, San Francisco, CA 94143-1234 (e-mail: mike.mccune@ucsf.edu).

Supported by the American Foundation for AIDS Research (107854-48-RGRL to J.M.M. and S.G.D.). Additional support was provided by in part by the University of California, San Francisco (UCSF)/Gladstone Center for AIDS Research (P30 AI27763), the Hurlbut-Johnson Fund administered by the AIDS Research Institute at UCSF (to R.M.D.), the UCSF/GIVI Center for AIDS Research (to R.M.D. and S.A.Y.), NIAID (U19 AI096109 to J.M.M. and S.G.D.), R37 AI040312 (to J.M.M.), K23 CA157929 (to M.S.), R24 AI067039 (to J.N.M.), and F32 AI091534 (to R.M.D.), the California HIV/AIDS Research Program (ID09-SF-067 to P.W.H.), the UCSF Clinical and Translational Science Institute (RR024131-01), and the US Department of Veterans Affairs (1 IK2 CX000520-01 to S.A.Y.).

The authors have no conflicts of interest to disclose.

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Received August 23, 2013

Accepted August 23, 2013

© 2014 by Lippincott Williams & Wilkins