From the Guidelines
Low Immunoglobulin A (IgA) in serum typically indicates Selective IgA Deficiency (SIGAD) if the level is less than 7 mg/dL, with normal serum IgG and IgM levels, and other causes of hypogammaglobulinemia have been excluded 1.
Key Points
- Definition of SIGAD: Serum IgA level of less than 7 mg/dL, with normal serum IgG and IgM levels, and other causes of hypogammaglobulinemia excluded 1.
- Clinical Associations: Most patients with SIGAD are asymptomatic, but some may experience respiratory and gastrointestinal tract infections, atopy, autoimmune diseases, celiac disease, and malignancy 1.
- Management: Long-term vigilance is recommended, with monitoring for complications and consideration of IgG replacement therapy if necessary 1.
- Risk of Anaphylactic Reactions: Patients with IgA deficiency may be at risk for anaphylactic reactions to blood products, although the risk is unclear and practices vary 1.
Important Considerations
- Diagnostic Threshold: A serum IgA level of less than 7 mg/dL is required for a diagnosis of SIGAD, as levels between 7 mg/dL and the lower limit of normal are not considered clinically significant 1.
- Prevalence: SIGAD is a common immunologic abnormality, affecting approximately 1 in 300 to 700 white subjects in the United States, with a higher prevalence in male patients and a family history of SIGAD or CVID in 20% to 25% of affected subjects 1.
From the Research
Definition and Prevalence of Low Immunoglobulin A (IgA)
- Low Immunoglobulin A (IgA) is defined as a decreased serum level of IgA in the presence of normal levels of other immunoglobulin isotypes 2, 3, 4.
- The international consensus definition of IgA deficiency is a level of 0.07g/l after the age of four years in the absence of IgG and IgM deficiencies 2.
- The prevalence of IgA deficiency ranges from 1:223 to 1:1000 in community studies and from 1:400 to 1:3000 in healthy blood donors 4.
Clinical Manifestations of Low IgA
- Patients with IgA deficiency may present with recurrent infections of the respiratory and gastrointestinal tracts, allergic disorders, and autoimmune manifestations 3, 4, 5.
- The most prevalent clinical manifestations of IgA deficiency include infections (64.8%), followed by allergic diseases (26.16%) and autoimmunity (22.0%) 5.
- Common infections associated with IgA deficiency include respiratory tract infections, fungal infections, and gastrointestinal infections 5.
- Autoimmune disorders associated with IgA deficiency include celiac disease, inflammatory bowel disease, and rheumatoid arthritis 5.
Risk of Infection with Low IgA
- Sustained, very low levels of IgA are associated with significantly increased risks of infections, primarily respiratory tract infections of bacterial origin 6.
- However, IgA deficiency appears to be better tolerated than deficiencies in other immunoglobulin isotypes, such as IgG and IgM 6.
- Replenishment of IgG in patients with hypogammaglobulinemia reduces the infection risk to background if IgG levels are maintained at approximately 500 mg/dL 6.