Abnormal antibody levels in intestine may promote inflammation in people with HIV-1

In people infected with HIV-1 virus, immune system cells in the intestinal tract may be unable to produce certain antibodies at the levels necessary to keep bacterial material from entering the bloodstream, according to a new study in PLOS Pathogens.

HIV-1 virus is known to cause extensive intestinal tract damage, allowing whole bacteria and tiny pieces of microbes living in the intestines to enter the bloodstream and activate the immune system. This can lead to chronic inflammation and AIDS, despite treatment with antiretroviral drugs. However, scientists have limited understanding of the mechanisms behind this process.

To better understand how HIV-1 impacts the intestinal tract, Zdenek Hel of the University of Alabama at Birmingham and colleagues took samples of intestinal secretions and blood plasma from 81 people infected with HIV-1, some of whom had received antiretroviral therapy, as well as from 25 non-infected people.

The researchers analyzed the samples using a technique called protein microarray analysis. In this technique, antibody proteins from the samples were exposed to fragments of different bacterial species and food materials. This allowed the scientists to determine what kinds of antibodies were produced in the intestines and in the bloodstream.

The analysis revealed that antibodies that allow the immune system to identify and respond to specific species of bacteria were present in intestinal secretions of both HIV-1-uninfected and -infected individuals. However, compared to non-infected people, the antibodies from people with HIV-1 were present primarily in a less mature form, called IgM, rather than the forms that are more efficient in binding the targets, called IgG and IgA. This suggests that immune system cells in the mucosal layer of the intestines may not be able to produce the antibodies necessary to keep bacterial fragments from entering the bloodstream. In addition, the accumulation of IgM in gut mucosa may cause inflammatory process by the formation of specific immune complexes.

"The results indicate that antibody-producing cells in the intestines of HIV-1-infected individuals have decreased capacity to switch from the production of IgM to IgA and IgG, the types of antibodies that normally restrict the translocation of bacterial components across the mucosal barrier. Immune activation induced by these microbial products may be the mechanism responsible for chronic inflammation that drives HIV-1 pathogenesis and progression to AIDS, despite successful control of HIV-1 replication by antiretroviral therapy", says Dr. Hel.

This study involved a relatively small number of patients and did not include direct analysis of intestinal tract cells. Nonetheless, the findings could improve our understanding of how HIV-1 undermines the immune system and inform research into potential new treatments.

Article: Dysregulation of Systemic and Mucosal Humoral Responses to Microbial and Food Antigens as a Factor Contributing to Microbial Translocation and Chronic Inflammation in HIV-1 Infection, Hel Z, Xu J, Denning WL, Helton ES, Huijbregts RPH, Heath SL, et al., PLOS Pathogens, doi:10.1371/journal.ppat.1006087, published 26 January 2017.