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, 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

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.

Trial registration: ClinicalTrials.gov NCT01313910.

Figures

Fig. 1
Fig. 1
Immunofluorescent antibody assay for T-lymphocyte populations in duodenal tissue.
Fig. 2
Fig. 2
Gastrointestinal questionnaire.
Fig. 3
Fig. 3
Intestinal permeability and absorptive function.
Fig. 4
Fig. 4
Mucosal immune reconstitution.
Fig. 5
Fig. 5
Biomarkers of inflammation, enterocyte damage, and collagen kinetics.

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