Microbiome modulator: Study shows Immunoglobulin A mediates microbe interaction for disease regulation

30 May 2023 --- Scientists from the Children’s Hospital of Philadelphia (CHOP) are one step closer to identifying why deficiencies in Immunoglobulin A (IgA), an antibody blood protein in the immune system, display symptoms in some and not others.

The key to solving the puzzle lies in the variability of IgA levels in the blood versus the intestines, as the antibody fine-tunes the body’s interaction with microbes. 

While IgA is the most common primary immune deficiency worldwide, its behavior remains a mystery to physicians and researchers. Some people with the disorder have recurrent infections, autoimmune diseases or allergies, while others have no symptoms and only become aware of their IgA-deficient status through random blood testing. 

“Right now, if we identify IgA deficiency in a patient through a blood test, we have no way of knowing whether the patient will become symptomatic if they aren’t already and we don’t know whether or when they might go on to develop a more serious immune deficiency,” explains Dr. Sarah Henrickson, assistant professor and attending physician, division of allergy and immunology at CHOP.

Low-sodium and nutrient-rich foods
According to Health Essentials, people with kidney diseases IgA nephropathy (IgAN) or C3G should follow a renal diet, which emphasizes low levels of sodium, phosphorus and potassium. Kidney diseases are often associated with conditions such as heart disease and diabetes, which have complicated dietary guidelines. 

“When you’re living with kidney disease, what you eat may become more restrictive with time. People with kidney failure or who are on dialysis benefit from the renal diet, which emphasizes low levels of sodium, phosphorus and potassium,” says Dr. Jonathan Taliercio, a nephrologist at Cleveland Clinic, Lerner School of Medicine.The behavior of IgA remains a mystery to physicians and researchers despite it being the most common primary immune deficiency globally.  

However, he recommends that people who do not have kidney disorders keep their sodium levels low and eat nutrient-rich whole foods. “A lot of us can get caught up in really complicated diets and cutting out certain nutrients for one reason or another,” says Taliercio.

“But if you can just focus on limiting your sodium intake and eating nutritious foods, that’s going to be good for your kidney function and your overall health.” 

The American Heart Association recommends an ideal limit of 1,500 mg of sodium daily. Using less salt during cooking and reading nutrition labels go a long way in lowering sodium levels. 

Regulating influx of microbes
The current study, published in Science Immunology, is a starting point in demonstrating that IgA is a catalyst that regulates microbes in the body.

IgA restrains the systemic immune response to these commensal microbes and limits the development of systemic immune dysregulation. 

“Our paper lays the groundwork for being able to answer these critically important questions by providing a lens into how IgA and the microbiome interact and how an imbalance in that interaction could lead to symptomatic disease,” says Henrickson.

IgA, which is mainly found in the respiratory and digestive tracts, blood, saliva, tears and breastmilk, is crucial to fighting disease.

The researchers analyzed the blood samples of 19 pediatric patients with IgA deficiency and 13 pediatric control patients. They set out to determine how mucosal antibodies like IgA and immunoglobulin M and system antibodies like IgG interact with mucosal microbes and how IgA deficiency affects the equilibrium of the immune system.

By Inga de Jong