Anti-IgA Antibodies

Anaphylactic reactions can be associated with almost any type of blood component and are life-threatening. Fortunately, they are uncommon events, occurring with an estimated incidence of 1 per 40,000 units transfused. 

Absolute IgA deficiency (<0.05 mg/dL) or an IgA subclass deficiency puts a patient at higher risk of having an anaphylactic reaction. Approximately 1 in 1200 people are totally IgA deficient and have detectable anti-IgA antibody. These patients may have an anaphylactic reaction when they are transfused with a blood component containing IgA antibodies.  When anti-IgA antibody binds to IgA in transfused plasma, complement is activated, resulting in anaphylaxis. 

Symptoms usually appear within 45 minutes after the start of the transfusion and consist of sudden onset of flushing and hypertension followed by hypotension, tachycardia, widespread edema, laryngeal edema, bronchospasm, and shock. Sometimes GI symptoms such as abdominal cramping, nausea, vomiting, and diarrhea can occur within minutes of starting the transfusion.

IgA deficiency is only one of many causes of anaphylactic transfusion reactions. Other reported causes of anaphylactic reactions include:  

• The recipient may have preformed antibodies to transfused donor allergens, including foods, medications or chemicals.
• Transfusion of polymorphic plasma proteins such as albumin, haptoglobin, C3, C4, and transferrin
• Bedside leukoreduction of components for patients receiving ACE inhibitors
• Transfusion of plasma or platelets to patients with Chido or Rogers antibodies
• Transfusion of bioactive lipids, CD40 ligand and cytokines that accumulate in stored products 
• Passive transfer of IgE antibodies to environmental antigens, high concentrations of histamine or other products of donor mast cell degranulation
• Haptoglobin deficiency

In many cases the cause of the anaphylactic reaction is not identified.

IgA deficiency is diagnosed by measuring quantitative immunoglobulin levels on a pretransfusion specimen. Unfortunately, most nephelometric methods for measuring IgA have a lower limit of detection of 5 mg/dL, which is not sensitive enough to diagnose absolute IgA deficiency.  A more sensitive enzyme-linked immunosorbent assay (ELISA) method with a sensitivity of 0.02 mg/dL is required to determine which individuals are truly IgA deficient. Only those with true IgA deficiency (i.e. levels below 0.05 mg/dL) may develop anti-IgA antibodies.

If IgA is deficient, serum can be sent to a reference laboratory for anti-IgA antibody determination. 

Specimen requirement is one red top or SST tube

Reference value is negative.

References

Palmer DS, O'Toole J, Montreuil T, Scalia V, Goldman M. Evaluation of Particle Gel Immunoassays for the Detection of Severe Immunoglobulin a Deficiency and Anti-Human Immunoglobulin a Antibodies. Transfusion 2012; 52: 1792-8.

Sandler SG. How I Manage Patients Suspected of Having Had an Iga Anaphylactic Transfusion Reaction. Transfusion 2006; 46: 10-3.