Immunoglobulin A (IgA) is a class of antibody protein produced by plasma cells and is a fundamental component of the immune system. When a serum test reveals an elevated IgA level, it signals an intensified immune response or an issue with antibody regulation or clearance. The elevated result is not a diagnosis but rather an indicator of an underlying process, such as an infection, chronic inflammation, or a disorder affecting the immune system. Understanding the source of this elevation requires investigation into the body’s current state of health.
The Function and Measurement of IgA
IgA is primarily recognized as the body’s first line of defense, with the majority existing as secretory IgA (sIgA) on mucosal surfaces like the respiratory and gastrointestinal tracts. This dimeric form contains a secretory component that protects it from degradation, allowing it to neutralize pathogens directly at the point of entry. Secretory IgA functions through immune exclusion, trapping foreign substances in mucus and preventing them from attaching to epithelial cells.
The IgA measured in a serum blood test is predominantly the monomeric form, known as serum IgA, which circulates throughout the bloodstream. Serum IgA accounts for about 15% of all immunoglobulins. A quantitative serum IgA test measures the total concentration of this antibody class. Although serum IgA is distinct from secretory IgA, its elevated presence often reflects hyperactivity in the mucosal immune system, which is the largest antibody-producing compartment.
Acute Conditions That Elevate IgA
An elevated serum IgA result can frequently be a temporary finding, representing a normal immune reaction to a recent pathogen exposure. Acute infections, particularly those affecting mucosal surfaces, commonly trigger this transient rise. For example, a viral respiratory infection stimulates the mucosal-associated lymphoid tissue (MALT) to generate IgA to combat the virus.
Once the infection is cleared, plasma cells reduce IgA production, and the serum level typically returns to its baseline. Transient inflammatory states, such as a severe allergic reaction or a localized skin condition like contact dermatitis, can also cause a temporary elevation. In these cases, the elevated IgA level is considered a polyclonal response, reflecting a broad, short-lived immune activation across many different IgA antibodies.
Chronic Systemic Diseases Causing High IgA
When IgA levels are persistently high, the cause is often a chronic, systemic condition involving long-term inflammation, impaired clearance, or unregulated antibody production. Chronic infections, such as HIV or hepatitis B and C, lead to sustained immune stimulation and chronically elevated IgA. The continued presence of the pathogen drives the immune system to maintain increased antibody output.
Chronic liver disease, including alcoholic cirrhosis and non-alcoholic steatohepatitis (NASH), is a frequent cause of IgA elevation. The liver clears circulating IgA immune complexes from the bloodstream. When liver function is compromised, this clearance fails, leading to the accumulation of IgA in the serum, a phenomenon noted in portal cirrhosis.
Autoimmune and inflammatory disorders also contribute to persistent IgA elevation by causing chronic immune activation. Conditions like IgA nephropathy, where IgA deposits in the kidneys, and IgA vasculitis (Henoch-Schönlein Purpura) are linked to abnormal IgA metabolism and deposition. Systemic diseases such as rheumatoid arthritis, Systemic Lupus Erythematosus (SLE), and inflammatory bowel disease (IBD) can also feature elevated IgA as part of a generalized hypergammaglobulinemia.
A more concerning cause involves disorders of the plasma cells that produce IgA. Monoclonal Gammopathy of Undetermined Significance (MGUS) occurs when a single clone of plasma cells produces an excess of identical IgA molecules, called a monoclonal protein or M-spike. If the IgA level is very high (above 4 g/L) or if a monoclonal spike is identified, it raises suspicion for IgA Multiple Myeloma, a cancer characterized by the uncontrolled production of this abnormal protein.
The Diagnostic Path Following an Elevated Result
Following the initial detection of elevated serum IgA, a healthcare provider begins clinical correlation to determine the underlying cause. This involves reviewing the patient’s history for symptoms of acute infection or chronic disease, often followed by repeating the IgA test to confirm persistence. Differentiating between a temporary and a chronic cause directs the subsequent diagnostic workup.
Further blood work typically includes a quantitative panel of all major immunoglobulins (IgG, IgM, and IgA) to determine if the elevation is isolated or globally increased. Serum Protein Electrophoresis (SPEP) with immunofixation is often ordered to check for a monoclonal protein, which points toward a plasma cell disorder like MGUS or Myeloma. A polyclonal increase supports a diagnosis of chronic inflammation or infection.
Tests to assess organ function are also performed, especially liver function tests (LFTs) and a urinalysis to check for protein or blood in the urine, which could indicate IgA nephropathy. Depending on the clinical picture, specific autoantibody tests may screen for autoimmune conditions, such as tissue transglutaminase IgA for Celiac Disease. The IgA result guides the investigation toward the specific disease process requiring attention and treatment.