Selective IgA2 deficiency in a patient with small intestinal Crohn's disease

The human IgA response is composed of two structurally different subclasses termed IgA1 and IgA2. Compared to IgA1, IgA2 has a shorter hinge region, which makes it more resistant to bacterial proteases. IgA1 is produced both systemically and in mucosal surfaces, whereas IgA2 is mostly confined to the intestines. While the overall IgA response is known to be involved in intestinal homeostasis, the specific contribution of IgA1 and IgA2 remains largely unknown (Chen 2020). Selective IgA deficiency (SIgAD) is the most prevalent primary immune deficiency. About half of SIgAD cases are associated with heterogeneous but generally mild clinical manifestations. Anecdotal evidence of IgA2 deficiency is available (van Loghem 1983, Ozawa 1986, Engstrom 1990), however no associations with clinical manifestations have been reported. Here, we describe the occurrence of a selective IgA2 deficiency in a patient (CD068) with small intestinal Crohns disease (CD). The patient had undetectable IgA2+ cells and secreted IgA2 antibody in both intestine and circulation. Among other features, patient CD068 presented with duodenal and ileal inflammation. To our knowledge, this is the first case of IgA2 deficiency with a potential link to IBD, which might shed new insights into potential IgA2-specific functions.