Serum-derived bovine immunoglobulin isolate increases peripheral and mucosal CD4 T cell count in patients with HIV enteropathy

Oral serum-derived bovine immunoglobulin improves duodenal immune reconstitution and absorption function in patients with HIV enteropathy David M. Asmuth a,b , Zhong-Min Ma c,d , Anthony Albanese b , Netanya G. Sandler e , Sridevi Devaraj f , Thomas H. Knight a , Neil M. Flynn a , Tammy Yotter a , Juan-Carlos Garcia a , Emily Tsuchida g , Tsung-Teh Wu h , Daniel C. Douek e and Christopher J. Miller b,c Objectives: To examine the impact of serum-derived bovine immunoglobulin, an oral medical food known to neutralize bacterial antigen and reduce intestinal inflammation, on restoration of mucosal immunity and gastrointestinal function in individuals with HIV enteropathy. Design: Open-label trial with intensive 8-week phase of bovine serum immuno- globulin (SBI) 2.5 g twice daily with a 4-week washout period and an optional 9-month extension study. Methods: HIV enteropathy was defined as chronic gastrointestinal symptoms including frequent loose or watery stools despite no identifiable, reversible cause. Upper endoscopy for tissue immunofluorescent antibody assay and disaccharide gut permeability/absorption studies were performed before and after 8 weeks of SBI to test mucosal immunity and gastrointestinal function. Blood was collected for markers of microbial translocation, inflammation, and collagen kinetics. A validated gastro- intestinal questionnaire assessed changes in symptoms. Results: All eight participants experienced profound improvement in symptoms with reduced bowel movements/day (P ¼ 0.008) and improvements in stool consistency (P ¼ 0.008). Gut permeability was normal before and after the intervention, but D -xylose absorption increased in seven of eight participants. Mucosal CD4 þ lymphocyte densities increased by a median of 139.5 cells/mm 2 from 213 to 322 cells/mm 2 (P ¼ 0.016). Intestinal-fatty acid binding protein (I-FABP), a marker of enterocyte damage, initially rose in seven of eight participants after 8 weeks (P ¼ 0.039), and then fell below baseline in four of five who continued receiving SBI (P ¼ 0.12). Baseline serum I-FABP levels were negatively correlated with subsequent rise in mucosal CD4 þ lymphocyte densities (r ¼ 0.74, P ¼ 0.046). Conclusion: SBI significantly increases intestinal mucosal CD4 þ lymphocyte counts, improves duodenal function, and showed evidence of promoting intestinal repair in the s 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins setting of HIV enteropathy. AIDS 2013, 27:2207–2217 a University of California Davis Medical School, b Veterans Administration Northern California Healthcare System, Sacramento, University of California - Davis, d Center for Comparative Medicine, Davis, California, e Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, f Baylor College of Medicine and Texas Children’s Hospital, Houston, Texas, g CARES Clinic, Sacramento, California, and h Mayo Clinic, Rochester, Minnesota, USA. Correspondence to David M. Asmuth, MD, Professor of Medicine, Division of Infectious & Immunologic Diseases, UC Davis Medical Center, 4150 V Street, PSSB G500, Sacramento, CA 95817, USA. Tel: +1 916 734 8695; fax: +1 916 734 7766; e-mail: david.asmuth@ucdmc.ucdavis. edu Received: 4 April 2013; revised: 2 May 2013; accepted: 3 May 2013. c DOI:10.1097/QAD.0b013e328362e54c ISSN 0269-9370 Q 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivitives 3.0 License, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially. Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.