Immunoglobulin A (IgA) is a major class of antibody that plays a protective role in the body’s defense system. When the level of this specific antibody is low, the condition is referred to as IgA deficiency. This state represents a significant impairment in the body’s ability to mount a complete immune response against certain types of invaders. Low IgA levels can stem from both inherited genetic defects and factors acquired later in life.
Understanding Immunoglobulin A and Mucosal Immunity
Immunoglobulin A is the most abundantly produced antibody in the body. While a portion of IgA circulates in the blood as a monomeric molecule, its primary function occurs at the mucosal surfaces. Here, IgA is secreted as a more complex structure known as Secretory IgA (sIgA).
The sIgA molecule is typically a dimer, linked together by a small protein called the J-chain. This complex is then transported across the epithelial cells lining the mucosal surface, acquiring an additional protective component called the secretory component. This structural addition makes sIgA highly resistant to degradation by enzymes found in harsh environments, such as the digestive tract.
The main purpose of sIgA is “immune exclusion,” which involves binding to pathogens and toxins to physically block them from attaching to or penetrating the body’s cells. This mechanism acts as a first line of defense, neutralizing threats at the point of entry before they can cause a systemic infection.
Primary Genetic Causes of Low IgA
The most frequent cause of persistently low IgA is a condition known as Selective IgA Deficiency (SIgAD). This diagnosis is made when an individual has low or undetectable levels of IgA but maintains normal levels of the other major antibodies, Immunoglobulin G and Immunoglobulin M. SIgAD is primarily a congenital disorder, and is often linked to a genetic predisposition.
The underlying mechanism involves a defect in the maturation process of B cells. B cells that are meant to differentiate into IgA-secreting plasma cells fail to complete this final step of development. While these B cells may express IgA on their surface, they cannot fully mature to become the factories that secrete the antibody into the bloodstream and mucosal fluids.
Genetic factors appear to influence susceptibility, with SIgAD showing a familial inheritance pattern in approximately 20% of cases. Researchers have identified associations with specific genes within the Major Histocompatibility Complex (MHC) region on chromosome 6. Mutations in the TACI gene, which is involved in B-cell signaling and antibody class switching, have also been found in a subset of patients. Although many cases are considered idiopathic, the persistent, lifelong nature and genetic links classify SIgAD as a primary, inherited failure of the immune system.
Secondary and Transient Causes
Low IgA levels can also be acquired later in life or occur secondary to another underlying health issue. Medications are known to interfere with B-cell function and antibody production, leading to drug-induced IgA deficiency. Anticonvulsant drugs, such as phenytoin and valproic acid, have been documented to cause this side effect in some patients. Immunosuppressive agents, including cyclosporine and certain chemotherapy drugs, can also suppress the production of IgA and other immunoglobulins.
Conditions that disrupt the immune system or the mucosal environment can also lead to secondary deficiency. For instance, Celiac Disease, an autoimmune disorder affecting the small intestine, is strongly associated with SIgAD. Some patients with SIgAD may also progress to a more severe condition called Common Variable Immunodeficiency (CVID), which involves low levels of IgG and sometimes IgM in addition to IgA.
Transient hypogammaglobulinemia of infancy (THI) is a temporary cause observed in young children. Infants are born with their mother’s IgG antibodies, and their own IgA production takes time to fully develop. IgA production often normalizing by three to five years of age.