Oral serum-derived bovine immunoglobulin improves duodenal immune reconstitution and absorption function in patients with HIV enteropathy

David M. Asmuth, Zhong Min Ma, Anthony Albanese, Netanya G. Sandler, Sridevi Devaraj, Thomas H. Knight, Neil M. Flynn, Tammy Yotter, Juan Carlos Garcia, Emily Tsuchida, Tsung Teh Wu, Daniel C. Douek, Christopher J. Miller

Research output: Contribution to journalArticle

47 Scopus citations

Abstract

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 immunoglobulin (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 gastrointestinal questionnaire assessed changes in symptoms. Results: All eight participants experienced profound improvement in symptoms with reduced bowel movements/day (P=0.008) and improvements in stool consistency (P=0.008). Gut permeability was normal before and after the intervention, but D-xylose absorption increased in seven of eight participants. Mucosal CD4+ lymphocyte densities increased by a median of 139.5 cells/mm2 from 213 to 322 cells/mm2 (P=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=0.039), and then fell below baseline in four of five who continued receiving SBI (P=0.12). Baseline serum I-FABP levels were negatively correlated with subsequent rise in mucosal CD4+ lymphocyte densities (r= -0.74, P=0.046). Conclusion: SBI significantly increases intestinal mucosal CD4+ lymphocyte counts, improves duodenal function, and showed evidence of promoting intestinal repair in the setting of HIV enteropathy.

Original languageEnglish (US)
Pages (from-to)2207-2217
Number of pages11
JournalAIDS
Volume27
Issue number14
DOIs
StatePublished - Sep 10 2013

Keywords

  • Bovine immunoglobulin
  • D-xylose absorption
  • Gastrointestinal associated lymphoid tissue
  • Gut permeability
  • HIV enteropathy
  • Immune reconstitution
  • Immunohistochemistry
  • Intestinal fatty acid binding protein
  • Monocyte chemotaxis protein-1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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    Asmuth, D. M., Ma, Z. M., Albanese, A., Sandler, N. G., Devaraj, S., Knight, T. H., Flynn, N. M., Yotter, T., Garcia, J. C., Tsuchida, E., Wu, T. T., Douek, D. C., & Miller, C. J. (2013). Oral serum-derived bovine immunoglobulin improves duodenal immune reconstitution and absorption function in patients with HIV enteropathy. AIDS, 27(14), 2207-2217. https://doi.org/10.1097/QAD.0b013e328362e54c