IgA - The art of balancing between host protection and auto-immunity

The human body is daily exposed to possible pathogens such as bacteria, viruses, fungi and parasites, as well as to essential non-body food components. The immune system ensures that there is a good balance between tolerating important elements such as the nutrients in our diet on the one hand, and preventing and fighting infections on the other hand. The immune system does this efficiently together with the organs, tissues and cells in the body. Antibodies are important immunological mediators and are produced by our body in different forms called IgA, IgG, IgE, IgD and IgM. IgA is the most predominant antibody at mucosal surfaces and plays an important role in maintaining homeostasis. In the intestinal tract IgA regulates a healthy microbiota composition and it plays an important role in preventing infection and disease. In the unlikely event that pathogens do enter, IgA can form a layer around the pathogen thereby forming a complex. FcαRI-expressing immune cells are activated with IgA complexes and produce more pro-inflammatory compounds compared to activation with IgG complexes. This potent stimulation by IgA is beneficial in elimination of the pathogen. Unfortunately, it can also happen that IgA is not directed against a pathogen, but against the body's own molecules. This so-called auto-IgA can result in tissue damage such as occurs in various autoimmune diseases. Auto-IgA can activate immune cells that have FcαRI on their cell surface and cause a deteriorated condition of the patient. Blocking interactions between IgA and FcαRI is a promising new therapy for IgA-mediated diseases. To maintain the health of the human body, it is therefore important that IgA and the interaction between IgA and FcαRI remain in balance.