Abstract

Microbial signals have been linked to autoantibody induction. Recently, we found that purified anti-CD4 autoantibodies from the plasma of chronic HIV-1-infected patients under viral-suppressed antiretroviral therapy (ART) play a pathologic role in poor CD4+ T cell recovery. The purpose of the study was to investigate the association of systemic microbiome and anti-CD4 autoantibody production in HIV. Plasma microbiome from 12 healthy controls and 22 HIV-infected subjects under viral-suppressed ART were analyzed by MiSeq sequencing. Plasma level of autoantibodies and microbial translocation (LPS, total bacterial 16S rDNA, soluble CD14, and LPS binding protein) were analyzed by ELISA, limulus amebocyte assay, and qPCR. We found that plasma level of anti-CD4 IgGs but not anti-CD8 IgGs was increased in HIV+ subjects compared to healthy controls. HIV+ subjects with plasma anti-CD4 IgG > 50 ng/mL (high) had reduced microbial diversity compared to HIV+ subjects with anti-CD4 IgG ≤ 50 ng/mL (low). Moreover, plasma anti-CD4 IgG level was associated with elevated microbial translocation and reduced microbial diversity in HIV+ subjects. The Alphaproteobacteria class was significantly enriched in HIV+ subjects with low anti-CD4 IgG compared to patients with high anti-CD4 IgG even after controlling for false discovery rate (FDR). The microbial components were different from the phylum to genus level in HIV+ subjects with high anti-CD4 IgGs compared to the other two groups, but these differences were not significant after controlling for FDR. These results suggest that systemic microbial translocation and microbiome may associate with anti-CD4 autoantibody production in ART-treated HIV disease.

Details

Title
Distinct systemic microbiome and microbial translocation are associated with plasma level of anti-CD4 autoantibody in HIV infection
Author
Xu, Wanli 1 ; Luo, Zhenwu 2 ; Alekseyenko, Alexander V 3 ; Martin, Lisa 4 ; Zhuang Wan 2 ; Ling, Binhua 5 ; Qin, Zhiqiang 6 ; Heath, Sonya L 7 ; Maas, Kendra 8 ; Cong, Xiaomei 1 ; Jiang, Wei 9   VIAFID ORCID Logo 

 University of Connecticut School of Nursing, Storrs, Connecticut, USA 
 Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, USA 
 Program for Human Microbiome Research, Biomedical Informatics Center, Department of Public Health Sciences, Department of Oral Health Sciences, Medical University of South Carolina, Charleston, SC, USA 
 Division of Infectious Diseases, Department of Medicine, Medical University of South Carolina, Charleston, SC, USA 
 Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA, USA; Tulane National Primate Research Center, New Orleans, LA, USA 
 Departments of Genetics, Louisiana State University Health Sciences Center, Louisiana Cancer Research Center, New Orleans, LA, USA 
 Division of Infectious Diseases, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA 
 Microbial Analysis, Resources, and Services, University of Connecticut, Storrs, CT, USA 
 Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, USA; Division of Infectious Diseases, Department of Medicine, Medical University of South Carolina, Charleston, SC, USA 
Pages
1-12
Publication year
2018
Publication date
Aug 2018
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2094401302
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.