Why is Immunoglobulin A (IgA) High? Causes, Symptoms, and What to Do

A high immunoglobulin A (IgA) result means your blood contains more of this antibody than the laboratory's reference range. It usually reflects an immune system that is being kept busy – by a long-lasting infection, especially in the gut, by inflammatory bowel disease, or by chronic liver or autoimmune disease. Less often, raised IgA comes from a single clone of plasma cells, as in multiple myeloma, which is why an unexplained high result is usually followed by a protein electrophoresis test. A single high value does not confirm any diagnosis on its own.

What IgA is

IgA is one of the three main antibody classes measured in blood, together with IgG and IgM. It is the antibody the body relies on most at mucosal surfaces such as the gut and airways. The blood (serum) IgA test is different from secretory IgA measured in saliva, breast milk or stool.

Normal range

Reference ranges vary by laboratory, test method, age and sex, so read your result against the range printed on your own report. Some labs ask you not to eat or drink for 4 hours before the test.

Causes of high IgA

Doctors first sort a raised IgA into one of two patterns, because they have different meanings:

• Polyclonal increase – many different plasma cells make more antibody. This is the response to ongoing inflammation or infection.
• Monoclonal increase – one clone of plasma cells makes a single identical antibody (a "monoclonal protein" or "M-protein"). This needs further assessment.

Common causes (polyclonal)

• Chronic infections, especially of the gastrointestinal tract – persistent infection keeps stimulating IgA-producing cells in the gut lining.
• Inflammatory bowel disease (Crohn's disease and ulcerative colitis) – long-term gut inflammation drives antibody production.
• Chronic liver disease and cirrhosis – raise immunoglobulin levels in general.
• Autoimmune and chronic inflammatory diseases such as rheumatoid arthritis and lupus – the immune system is persistently activated.
• Other infections and recent immunisation – also stimulate antibody production.

Less common causes (monoclonal)

• Monoclonal gammopathy of undetermined significance (MGUS) – an M-protein is present, but its significance is not yet determined.
• Multiple myeloma – a cancer of plasma cells; it can produce an abnormal immunoglobulin, including IgA.
• Lymphoma and other blood cancers.

A note on IgA nephropathy

IgA nephropathy (Berger's disease) is a kidney disease in which clumps of IgA antibodies are deposited in the kidney filters, causing inflammation. Blood IgA is raised in some, but not all, people with IgA nephropathy, so a high IgA does not prove it and a normal IgA does not rule it out. Diagnosis requires a kidney biopsy. Its typical signs are pink or cola-coloured urine, foamy urine and swelling of the legs.

Symptoms

A high IgA level does not cause symptoms by itself. Any symptoms come from the underlying condition – the gut, liver, joint or other disease that is driving it. The signs that make doctors look specifically for multiple myeloma are bone damage, anaemia, frequent infections and kidney problems.

What usually happens next

1. Look at the whole picture. The result is interpreted together with your symptoms, your IgG and IgM levels and a complete blood count.
2. Serum protein electrophoresis (SPEP). This shows whether the increase is polyclonal or monoclonal. It is often requested after an abnormal immunoglobulin result, or when myeloma is suspected.
3. Immunofixation electrophoresis. If SPEP shows an abnormal band, immunofixation identifies which antibody type (IgG, IgA or IgM) is being overproduced.
4. Urine protein electrophoresis may be added if myeloma is a concern, and electrophoresis may be repeated at intervals to monitor a diagnosed condition.

What changes the interpretation: whether the rise is polyclonal or monoclonal, whether IgG and IgM are also raised, and whether there are signs of gut, liver, joint or kidney disease.

Low IgA and the coeliac (anti-tTG IgA) test

Low IgA is also common in searches, and it matters most for coeliac disease testing.

• Selective IgA deficiency is the most common primary immunodeficiency. IgG and IgM are normal. Most people have few or no symptoms; others have repeated chest or sinus infections, allergies, asthma or chronic diarrhoea. Other causes of low IgA include inherited antibody deficiencies, protein loss from the gut and multiple myeloma.
• Anti-tTG IgA (tissue transglutaminase IgA) is the main blood test for coeliac disease. Because it relies on IgA, labs check total IgA first: if total IgA is too low, a negative tTG-IgA result is not reliable, and IgG-based tests (tTG-IgG and DGP-IgG) are used instead.
• You need to keep eating gluten for a few weeks before coeliac testing; cutting it out can make the result falsely negative.
• A positive tTG-IgA usually leads to referral for an endoscopy with a small-bowel biopsy, which confirms the diagnosis.

Frequently asked questions

What does a high IgA mean? That your immune system is producing more IgA than usual, commonly because of chronic infection, inflammatory bowel disease, liver disease or an autoimmune condition. Less often it reflects a monoclonal protein, as in MGUS or myeloma.

What are the causes of raised IgA? Chronic gut and other infections, Crohn's disease and ulcerative colitis, cirrhosis and chronic liver disease, rheumatoid arthritis and lupus, recent immunisation, and, less commonly, MGUS, multiple myeloma or lymphoma.

Is high IgA a sign of cancer? Not necessarily. Many of the causes are infections or inflammatory, liver or autoimmune diseases. Raised IgA can also be seen in multiple myeloma, so a protein electrophoresis test is used to check whether a monoclonal protein is present – the pattern that needs further assessment.

Is elevated IgA serious? It depends on the cause, not on the number alone. A single high result does not confirm anything; your doctor will interpret it with your symptoms and other tests.

What does low IgA mean? Usually selective IgA deficiency, which often causes no symptoms. It is important to know about before coeliac testing and before blood transfusions, because a few people with it react to IgA in donated blood products.

What is anti-tTG IgA? The main blood test for coeliac disease. A positive result means coeliac disease is likely and is usually confirmed by a small-bowel biopsy. It is only reliable if your total IgA is normal and you are still eating gluten.

When to see a doctor

A raised IgA found on a routine test is worth discussing with your doctor soon, so it can be put in context and a protein electrophoresis arranged if needed. Book an appointment sooner if you also have persistent bowel symptoms, unexplained weight loss, bone pain, frequent infections, or blood or foam in your urine.

Sources

1. Quantitative nephelometry test — MedlinePlus Medical Encyclopedia, U.S. National Library of Medicine
2. Immunoglobulins (IgA, IgG, IgM) — Testing.com
3. Protein Electrophoresis, Immunofixation Electrophoresis — Testing.com
4. Selective Immunoglobulin A (IgA) Deficiency — Merck Manual Consumer Version
5. IgA Nephropathy — NIDDK
6. Celiac Disease Antibody Tests — Testing.com
7. Celiac Disease Screening — MedlinePlus, U.S. National Library of Medicine
8. Elevated baseline serum IgA may predict earlier proteinuria remission in IgA nephropathy patients — International Journal of Clinical and Experimental Pathology (PMC)

Decisions about your health should always be made in consultation with your healthcare provider.