Why is Immunoglobulin G (IgG) high? Causes, symptoms, and what to do

A high immunoglobulin G (IgG) means your immune system is producing more antibodies than usual, most often because of a long-lasting infection, inflammation, liver disease or an autoimmune condition such as rheumatoid arthritis. Less often, a single type of antibody is being overproduced by a blood cancer such as multiple myeloma, which is why a very high IgG is followed by further tests. A high IgG causes no symptoms of its own. Note that a total IgG level is different from an IgG test against a specific germ (such as "CMV IgG positive"), which only shows past exposure; both are explained below.

What IgG is

Immunoglobulins are antibodies. Three types are measured routinely:

• IgM is the first antibody your body makes after exposure to a germ, giving short-term protection.
• IgG is the most specialised: it is made against a specific germ and "remembered" after the infection clears, so the body can respond faster next time. It is found in all body fluids, most of all in blood.
• IgA protects the lining of the airways and the gut.

Typical adult values

Ranges vary slightly between laboratories; use the range on your report.

Causes of high IgG

More common

• Chronic infection or inflammation. Ongoing immune stimulation drives antibody production across many types. Long-standing viral infections such as HIV and hepatitis are typical examples: HIV activates antibody-making cells broadly, and a raised IgG can be an early sign of it.
• Liver disease, including hepatitis and cirrhosis.
• Autoimmune disease, such as rheumatoid arthritis or lupus.
• Hyperimmunisation, that is, repeated strong immune stimulation.

Less common

• Blood cancers, mainly IgG multiple myeloma, where one abnormal antibody is overproduced. This often gives a very high level of one immunoglobulin type and low levels of the others, a pattern doctors look for. (Some other blood cancers, such as chronic lymphocytic leukaemia, more often LOWER antibody levels.)

Causes of low IgG

• Protein loss or poor nutrition: kidney disease, serious burns, malabsorption disorders, malnutrition.
• Conditions that reduce antibody production: complications of diabetes and kidney failure, leukaemia, and multiple myeloma (which can suppress normal antibodies).
• Medicines: certain chemotherapy drugs.
• Pre-eclampsia in pregnancy.
• Inherited immune deficiencies, such as common variable immunodeficiency (CVID) and agammaglobulinaemia.

Symptoms

A high IgG does not cause symptoms; any symptoms come from the cause, such as joint pain in rheumatoid arthritis or features of liver disease. A low IgG can make you prone to infections: frequent sinus, throat or ear infections, pneumonia or bronchitis, gut infections, or repeated infections with the same germ.

Specific IgG antibody tests: CMV, EBV, hepatitis B and others

Many tests measure IgG against one particular germ or target. These are yes/no answers about exposure, not measures of your total IgG. Because IgM comes first and IgG lasts, IgG usually points to a past or longer-standing infection, and IgM to a recent one, though there are exceptions.

• CMV IgG positive. You were infected with cytomegalovirus at some time in your life; the test does not tell when. CMV IgM alone cannot prove a new infection either, because it can also appear with a secondary infection (an old infection reactivating, or a new strain). If timing matters, as in pregnancy, an IgG avidity test helps: low avidity suggests a recent first infection. A change from IgG negative to IgG positive between two samples is clear evidence of a recent first infection.
• EBV IgG positive, IgM negative. Antibodies to the Epstein-Barr virus capsid (VCA IgG) appear early and persist for life, while VCA IgM usually disappears within four to six weeks. VCA IgG together with antibody to EBNA suggests a past infection, months to years earlier. Over 90% of adults have been infected with EBV.
• Anti-HBc IgG (total anti-HBc). This hepatitis B core antibody appears about 5 weeks after exposure and remains detectable indefinitely. On its own it means past or current infection; HBsAg, anti-HBs and sometimes IgM anti-HBc or HBV DNA are needed to tell which.
• H. pylori IgG. A blood antibody test cannot show whether the infection is active now or was in the past, so breath and stool tests are more commonly used. A positive H. pylori IgG therefore shows exposure at some time, not necessarily a current infection.
• IgG4. This measures one subclass of IgG. A raised level supports IgG4-related disease, an inflammatory condition that can affect the pancreas, bile ducts, salivary glands and other organs, but it is neither necessary nor sufficient for the diagnosis: it can be normal early on and raised in other conditions.
• AQP4-IgG. This is an autoantibody against aquaporin-4, a water channel in the nervous system. It is a marker of neuromyelitis optica spectrum disorder (NMOSD), which mainly affects the optic nerves and spinal cord, and helps distinguish it from multiple sclerosis.

What usually happens next

For an abnormal total IgG, a clinician reads it together with IgA and IgM and your other results, and may order serum and/or urine protein electrophoresis to check whether one antibody type is being overproduced. An immunoglobulin test alone cannot diagnose any condition. Some medicines can affect results, but do not stop any medicine unless your doctor advises it. Usually no preparation is needed, though some laboratories ask you not to eat or drink for 4 hours beforehand.

Frequently asked questions

What does CMV IgG positive mean? That you have had a cytomegalovirus infection at some point in your life. It does not mean you are ill now. In pregnancy, your doctor may add IgM and avidity testing to estimate when the infection happened.

Is IgG acute or chronic? IgG usually reflects a past or established infection, while IgM is the early, short-lived antibody of a new infection. Neither is perfectly reliable alone, so results are read as a pattern.

What does EBV IgG positive and IgM negative mean? Most often a past Epstein-Barr infection, especially if EBNA antibody is also positive. This is the usual result in adults.

What causes high immunoglobulin G? Chronic infections, liver disease, autoimmune diseases and long-standing inflammation are the usual causes. A very high level of IgG with low IgA and IgM needs checking for a blood cancer such as myeloma.

What do low IgG levels mean? Either antibodies are being lost (kidney disease, burns, malnutrition, malabsorption) or not made in enough amounts, because of an inherited immune deficiency, a blood cancer or chemotherapy. The main risk is more frequent infections.

What is an IgG blood test? It measures the amount of IgG antibody in your blood, usually together with IgA and IgM, to look for immune deficiency or overproduction.

When to see a doctor

A mildly high IgG found on routine testing, in someone who feels well, is worth discussing with your doctor at your next appointment, along with any long-standing conditions you have. It is worth seeing your doctor soon if you have repeated or unusually severe infections, unexplained weight loss or yellowing of the skin, or if a specific antibody result such as CMV, EBV or hepatitis B needs interpreting, especially during pregnancy. Seek urgent care for severe breathing difficulty, confusion or fainting.

Sources

1. Quantitative immunoglobulins — MedlinePlus, U.S. National Library of Medicine
2. Immunoglobulins Blood Test — MedlinePlus, U.S. National Library of Medicine
3. Laboratory Testing for CMV and Congenital CMV — Centers for Disease Control and Prevention
4. Laboratory Testing for Epstein-Barr Virus (EBV) — Centers for Disease Control and Prevention
5. Hepatitis B Surveillance Guidance — Centers for Disease Control and Prevention
6. Helicobacter Pylori (H. pylori) Tests — MedlinePlus, U.S. National Library of Medicine
7. Update on classification, diagnosis, and management of immunoglobulin G4-related disease — Chinese Medical Journal, via PMC
8. Aquaporin-4 in Neuromyelitis Optica Spectrum Disorders: A Target of Autoimmunity in the Central Nervous System — Biomolecules, via PMC
9. Hypergammaglobulinemia in treated and untreated people with HIV — PLoS One, via PMC
10. Prevalence and the impact of hypogammaglobulinemia in newly diagnosed chronic lymphocytic leukaemia — eJHaem, via PMC

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