High intestinal IgA associates with reduced risk of IgE-associated allergic diseases

Development of oral tolerance and its stimulation by probiotics are still incomprehensible. Microbial stimulation of the gut may induce a subtle inflammation and induce secretion of mucosal IgA, which participates in antigen elimination. In a cohort of allergy-prone infants receiving probiotics and prebiotics or placebo we studied intestinal IgA and inflammation in the development of eczema, food allergy, asthma, and rhinitis (allergic diseases). We performed a nested unmatched case-control study of 237 infants participating in a randomized double-blind placebo-controlled allergy-prevention trial using a combination of four probiotic strains pre-natally and during 6 months form birth. We measured faecal IgA, alpha1-antitrypsin (alpha1-AT), tumour necrosis factor-alpha (TNF-alpha), and calprotectin at the age of 3 and 6 months. By age 2 yr, 124 infants had developed allergic disease or IgE-sensitization (cases) and 113 had not (controls). In infants with high faecal IgA concentration at the age of 6 months, the risk of having any allergic disease before the age of 2 yr tended to reduce [odds ratio (OR: 0.52)] and the risk for any IgE-associated (atopic) disease reduced significantly (OR: 0.49). High faecal calprotectin at the age of 6 months associated also with lower risk for IgE-associated diseases up to age 2 yr (OR: 0.49). All faecal inflammation markers (alpha1-AT, TNF-alpha, and calprotectin) correlated positively with faecal IgA (p < 0.001). Probiotics tended to augment faecal IgA (p = 0.085) and significantly increased faecal alpha1-AT (p = 0.001). High intestinal IgA in early life associates with minimal intestinal inflammation and indicates reduced risk for IgE-associated allergic diseases.