Abstract
BackgroundBreakdown of the gut mucosal barrier during chronic HIV infection allows translocation of bacterial products such as lipopolysaccharides (LPS) from the gut into the circulation. Microbial translocation also occurs in inflammatory bowel disease (IBD). IBD serological markers are useful in the diagnosis of IBD and to differentiate between Crohn's disease (CD) and ulcerative colitis (UC). Here, we evaluate detection of IBD serological markers in HIV-infected patients with advanced disease and their relationship to HIV disease markers.MethodsIBD serological markers (ASCA, pANCA, anti-OmpC, and anti-CBir1) were measured by ELISA in plasma from AIDS patients (n = 26) with low CD4 counts (<300 cells/µl) and high plasma LPS levels, and results correlated with clinical data. For meta-analysis, relevant data were abstracted from 20 articles.ResultsIBD serological markers were detected in approximately 65% of AIDS patients with evidence of microbial translocation. An antibody pattern consistent with IBD was detected in 46%; of these, 75% had a CD-like pattern. Meta-analysis of data from 20 published studies on IBD serological markers in CD, UC, and non-IBD control subjects indicated that IBD serological markers are detected more frequently in AIDS patients than in non-IBD disease controls and healthy controls, but less frequently than in CD patients. There was no association between IBD serological markers and HIV disease markers (plasma viral load and CD4 counts) in the study cohort.ConclusionsIBD serological markers may provide a non-invasive approach to monitor HIV-related inflammatory gut disease. Further studies to investigate their clinical significance in HIV-infected individuals are warranted.
Highlights
CD4 T-cells in gut-associated lymphoid tissue (GALT) are primary target cells of HIV, and GALT is an important site for HIV replication and pathogenesis [1,2,3,4]
A serological pattern consistent with inflammatory bowel disease (IBD) was detected in 46% of AIDS patients; of these, 75% showed a Crohn’s disease (CD)-like pattern, while 25% had a ulcerative colitis (UC) pattern
Subjects were selected from a larger cohort of 119 AIDS subjects with CD4 counts,300 cells/ml described in a previous study [12] on the basis of high plasma LPS above the median value for AIDS patients in the study cohort (.80 pg/ml) levels; LPS levels were determined in the previous study using the Diazo-coupled Limulus amebocyte lysate (LAL) assay
Summary
CD4 T-cells in gut-associated lymphoid tissue (GALT) are primary target cells of HIV, and GALT is an important site for HIV replication and pathogenesis [1,2,3,4]. Later on, during chronic HIV infection, loss of GALT integrity and breaching of the gut mucosal barrier leads to microbial translocation [8,9,10], which is evidenced by the release of microbial products such as bacterial endotoxins (lipopolysaccharides (LPS), a component of gram negative bacteria) into the circulation (endotoxemia) [11]. IBD comprises a group of intestinal diseases characterized by chronic inflammation of the bowel; Crohn’s disease (CD) and ulcerative colitis (UC) are the common clinical subtypes of IBD. Breakdown of the gut mucosal barrier during chronic HIV infection allows translocation of bacterial products such as lipopolysaccharides (LPS) from the gut into the circulation. Microbial translocation occurs in inflammatory bowel disease (IBD). We evaluate detection of IBD serological markers in HIV-infected patients with advanced disease and their relationship to HIV disease markers
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