What is Immunoglobulin A (IgA)?

From the Guidelines

IgA, or Immunoglobulin A, is an antibody that plays a crucial role in immune function at mucous membranes, and its deficiency can lead to increased susceptibility to respiratory and gastrointestinal infections, as noted in patients with serum IgA levels of less than 7 mg/dL 1.

Definition and Function of IgA

IgA exists in two forms: secretory IgA found in mucous secretions and serum IgA circulating in the bloodstream. This antibody works by neutralizing pathogens, preventing them from attaching to epithelial surfaces, and maintaining the balance of beneficial bacteria in the gut. Some key points about IgA include:

• It is the most abundant antibody in secretions like saliva, tears, breast milk, and intestinal fluid, where it forms the first line of defense against pathogens.
• IgA deficiency is the most common primary immunodeficiency, affecting about 1 in 300 to 700 white subjects in the United States, as discussed in the context of Selective IgA Deficiency (SIGAD) 1.
• IgA levels can be measured through blood tests to diagnose conditions like IgA deficiency or IgA nephropathy, a kidney disease caused by IgA deposits in the kidneys.

Clinical Implications of IgA Deficiency

Understanding IgA's function helps explain why mucosal immunity is essential for overall health and protection against common infections. Key considerations in the management of IgA deficiency include:

• Patients with SIGAD should be monitored over time for the occurrence of complications, such as respiratory and gastrointestinal tract infections, atopy, autoimmune diseases, celiac disease, and malignancy 1.
• The risk of anaphylactic reactions to blood products in patients with IgA deficiency is considered small, but practices vary, with some centers opting to transfuse products from IgA-deficient donors or wash cells before transfusion 1.

From the Research

Definition and Structure of Immunoglobulin A (IgA)

• Immunoglobulin A (IgA) is the most abundantly produced antibody in humans 2, 3, 4, 5, 6.
• IgA is a unique class of immunoglobulin due to its multiple molecular forms, with two subclasses: IgA1 and IgA2 2, 5.
• IgA1 has a long hinge-region that is heavily O-glycosylated, whereas the IgA2 hinge-region is shorter but resistant to bacterial proteases prevalent at mucosal sites 2.
• Structurally, IgA in the mucosal surface is a polymeric structure, while serum IgA is monomeric 3.

Functions of IgA

• IgA is essential for immune homeostasis and education 2.
• Mucosal IgA plays a crucial role in maintaining the integrity of the mucosal barrier by immune exclusion of pathobionts while facilitating colonization with certain commensals 2, 3, 4, 6.
• IgA also mediates a variety of protective functions through interaction with specific receptors and immune mediators 6.
• In the circulation, monomeric IgA that has not been engaged by antigen plays a discrete role in dampening inflammatory responses 2.

Role of IgA in Mucosal Immunity

• Secretory IgA (sIgA) is one of the polymeric IgAs composed of dimeric IgA, J chain, and secretory component (SC) 3.
• sIgA plays an important role in the specific immunity and immunoregulation, in addition to its function of "immune exclusion" 3.
• IgA antibodies that target the mucosal surface are made up of two to five IgA monomers linked together by the joining chain, forming polymeric molecules 4.
• These IgA polymers are transported across mucosal epithelial cells by the polymeric immunoglobulin receptor pIgR, resulting in the formation of secretory IgA (SIgA) 4.