Understanding Abnormal Gut Antibodies May Lead to New HIV Treatments

Gut antibody imbalance may impact immune response to HIV.

The imbalance of antibodies in the gut of patients with HIV may be an important factor contributing to the failure of the gut to prevent an inflammatory microbial invasion of the bloodstream.

For the study, investigators used the novel technique protein microarray analysis to examine antibodies in fluid derived from the intestines of 81 patients with HIV and 25 uninfected controls.

In total, 39 different protein antigens from gut bacteria were used to bind antibodies from gut wash fluid, as well as various food antigen proteins. This allowed the investigators to test which types of antibodies were produced in HIV-positive and HIV-negative participants.

The results of the study, published in PLOS Pathogens, revealed that both infected and uninfected participants created antibodies against the bacterial and food antigens. However, the types of antibodies produced varied significantly between the 2 groups.

Patients with HIV had higher proportions of immunoglobulin M (IgM) compared with the antibody forms IgG and IgA, which are superior in binding antigens. The findings suggest that immune system cells located in the mucosa are unable to produce the types of antibodies needed to prevent bacterial fragments from entering the bloodstream, according to the investigators.

Additionally, the accumulation of IgM in the gut mucosa could form immune complexes that further exacerbate inflammation.

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

The results of the study showing that HIV is associated with significant elevation of IgM levels and decreased ratios of IgG/IgM and IgA/IgM are consistent with the loss of mucosal memory CD4+ T cells.