What is already known
The partial or total lack of Immunoglobulin A (IgA) — an antibody that helps the body fight disease, is the most common primary immune deficiency worldwide. Because IgA is mostly found in the respiratory and digestive tracts, scientists suspect it helps keep the gut microbiota in check. However, most people with IgA deficiency do not show symptoms related to uncontrolled gut bacteria.
What this research adds
Researchers analyzed blood and fecal samples from 19 children and adolescents with IgA deficiency and 13 healthy siblings. They found that in people who lack both blood and fecal IgA, bacteria are more likely to breach the gut barrier and travel to lymph nodes in the abdomen. These people have more clinical symptoms and evidence of immune dysregulation than those who lack blood IgA but not fecal IgA. In the gut, the presence of another type of antibody protein called IgM didn’t fully compensate for the absence of IgA, the team found.
Conclusions
The findings suggest that IgA can modulate the exposure and immune response to commensal microbes, and its levels determine the severity of immune dysregulation and clinical symptoms in people with IgA deficiency.
The partial or total lack of Immunoglobulin A (IgA) — an antibody that helps the body fight disease, is the most common primary immune deficiency worldwide. Now, researchers have found that the levels of IgA antibodies influence how well the immune system can maintain control of gut bacteria.
The findings, published in Science Immunology, suggest that IgA can modulate the exposure and immune response to commensal microbes, and its levels determine the severity of immune dysregulation and clinical symptoms in people with IgA deficiency.
IgA antibodies are mostly found in the respiratory and digestive tracts. Because of this, scientists suspect that IgA helps keep the gut microbiota in check. However, most people with IgA deficiency do not show symptoms related to uncontrolled gut bacteria.
To investigate how IgA deficiency affects the immune system, researchers led by Peyton Conrey at the Children’s Hospital of Philadelphia analyzed blood and fecal samples from 19 children and adolescents with IgA deficiency and 13 healthy siblings.
Breaching barriers
The researchers measured the levels of three types of antibodies — IgA, IgM, and IgG — and assessed the activation of the immune system. Although IgA, IgM and IgG recognized overlapping sets of microbes in healthy individuals, IgM antibodies didn’t full compensate for the absence of IgA in the gut, the researchers found.
The team also discovered that about 25% of children and adolescents with IgA deficiency had normal levels of IgA in their feces. In children and adolescents who lack both systemic and fecal IgA, bacteria were more likely to breach the gut barrier and travel to lymph nodes in the abdomen. These people were also more likely to develop immune dysregulation and clinical disease than those who lacked IgA only in their blood.
“Based on these results, we propose that IgA supports the intestinal barrier to keep the proper balance of commensal microbes interacting with the immune system, acting as a tuner to keep the immune system in check,” Silverman says.
Inflammatory environment
To validate their findings, the researchers studied mice that lacked IgA. Unlike healthy controls, these animals showed severe immune dysregulation and had live microbes in their fat tissues.
“Without IgA protecting the gut, commensal bacteria can get through, increasing a patient’s systemic exposure to these microbes and creating an inflammatory environment,” Silverman says.
The results suggest that IgA regulates the number of microbes the body sees every day, restraining immune responses to these microbes, the researchers say. However, they add, larger studies that investigate IgA levels in different tissues will help to determine if the findings could predict the course and outcomes of IgA deficiency in people.
