IgG

Immunoglobulin G

Immune & Inflammation

What is Immunoglobulin G?

Immunoglobulin G (IgG) is the most abundant antibody in the blood and extracellular fluid, accounting for approximately 75–80% of all serum immunoglobulins. IgG is a monomeric antibody produced by plasma cells during the secondary (memory) immune response, making it the predominant antibody of long-term immunity. It is the only immunoglobulin that crosses the placenta, providing passive immunity to the fetus and newborn during the first few months of life until the infant's own immune system matures.

IgG is divided into four subclasses—IgG1, IgG2, IgG3, and IgG4—each with distinct effector functions and half-lives. IgG1 is the most abundant subclass and is particularly effective at activating complement and mediating opsonization (coating pathogens for phagocytosis). IgG2 targets polysaccharide antigens found on encapsulated bacteria. IgG3 is the most potent complement activator but has the shortest half-life. IgG4 does not activate complement and is associated with chronic antigen exposure and IgG4-related disease. Quantitative IgG measurement is fundamental to diagnosing immunodeficiency syndromes, monitoring immunoglobulin replacement therapy, and evaluating gammopathies.

Why It Matters

IgG is the backbone of humoral immunity and immunological memory. Low IgG levels leave patients profoundly susceptible to recurrent bacterial infections, particularly with encapsulated organisms like Streptococcus pneumoniae and Haemophilus influenzae. Primary immunodeficiencies such as common variable immunodeficiency (CVID) and X-linked agammaglobulinemia are characterized by markedly low IgG and are treated with lifelong immunoglobulin replacement. Elevated monoclonal IgG is the hallmark of IgG myeloma, the most common type of multiple myeloma. Polyclonal IgG elevation occurs in chronic infections, autoimmune disease, and liver disease.

Normal Reference Ranges

GroupRangeUnit
Adults700–1,600mg/dL
Children (6–12 years)600–1,500mg/dL
Children (1–5 years)400–1,300mg/dL
Neonates700–1,300mg/dL (maternal)

Reference ranges may vary by laboratory. Always compare results to the ranges provided by your testing facility.

What High IgG Levels Mean

Common Causes

  • IgG multiple myeloma (monoclonal elevation)
  • Chronic infections (HIV, hepatitis, tuberculosis)
  • Autoimmune diseases (SLE, rheumatoid arthritis, sarcoidosis)
  • Liver disease (cirrhosis, chronic hepatitis)
  • IgG4-related disease
  • Monoclonal gammopathy of undetermined significance (MGUS)
  • Chronic inflammatory conditions

Possible Symptoms

  • Bone pain and pathologic fractures (in myeloma)
  • Fatigue and weakness
  • Recurrent infections (immune paresis in myeloma)
  • Weight loss
  • Kidney dysfunction
  • Hyperviscosity symptoms (rare, more common with IgM)
  • Organ swelling and fibrosis (IgG4-related disease)

What to do: Elevated IgG requires serum protein electrophoresis (SPEP) with immunofixation to distinguish polyclonal from monoclonal elevation. Monoclonal IgG (M-spike) warrants myeloma workup including serum free light chains, 24-hour urine for Bence-Jones protein, skeletal survey or PET-CT, and bone marrow biopsy. Polyclonal elevation suggests chronic infection, autoimmune disease, or liver disease—evaluate with targeted testing based on clinical presentation. IgG4 subclass should be checked if IgG4-related disease is suspected.

What Low IgG Levels Mean

Common Causes

  • Common variable immunodeficiency (CVID)
  • X-linked agammaglobulinemia (Bruton disease)
  • IgG subclass deficiency
  • Nephrotic syndrome (urinary protein loss)
  • Protein-losing enteropathy
  • Medications (rituximab, corticosteroids, immunosuppressants)
  • Chronic lymphocytic leukemia
  • Severe burns or protein malnutrition

Possible Symptoms

  • Recurrent sinopulmonary infections (sinusitis, bronchitis, pneumonia)
  • Recurrent ear infections
  • Chronic diarrhea
  • Invasive infections (sepsis, meningitis)
  • Bronchiectasis from chronic lung infections
  • Failure to thrive in children

What to do: Low IgG with recurrent infections requires comprehensive immune evaluation including IgG subclasses, IgA, IgM, vaccine response titers (pneumococcal, tetanus), and lymphocyte enumeration. CVID is diagnosed when IgG is significantly low with impaired vaccine responses and other causes are excluded. Treatment is lifelong immunoglobulin replacement therapy (IVIG or subcutaneous immunoglobulin) to maintain trough IgG levels above 500 mg/dL. Prophylactic antibiotics and aggressive treatment of infections are also important.

When Is IgG Testing Recommended?

  • When recurrent bacterial infections suggest immunodeficiency
  • When evaluating an abnormal serum protein electrophoresis
  • When multiple myeloma is suspected
  • To monitor immunoglobulin replacement therapy
  • When evaluating nephrotic syndrome or protein-losing conditions
  • As part of an immunoglobulin panel in immune workup

Frequently Asked Questions

IgG and IgM serve different roles in the immune response. IgM is the first antibody produced during a new infection (primary response) and indicates acute or recent infection. IgG is produced later during the secondary response and represents long-term immunity and immunological memory. IgG has a much longer half-life (21 days vs. 5 days for IgM) and is the predominant antibody in blood. IgG is smaller and can cross the placenta to protect the fetus, while the larger pentameric IgM cannot. In serologic testing, IgM-positive/IgG-negative means acute infection, while IgM-negative/IgG-positive means past infection or immunization.
Common variable immunodeficiency (CVID) is the most common symptomatic primary immunodeficiency, affecting approximately 1 in 25,000–50,000 people. It is characterized by low IgG (usually with low IgA and/or IgM), impaired antibody responses to vaccines, and recurrent bacterial infections—particularly sinopulmonary infections. CVID can present at any age but most commonly in the second or third decade. Beyond infections, CVID patients have increased rates of autoimmune disease, granulomatous inflammation, and lymphoma. Treatment is lifelong immunoglobulin replacement therapy, given intravenously (every 3–4 weeks) or subcutaneously (weekly or biweekly), targeting trough IgG levels that minimize infections.
IgG subclass deficiency occurs when one or more of the four IgG subclasses is below normal while total IgG may be normal or only mildly reduced. IgG2 subclass deficiency is the most clinically significant, as IgG2 targets polysaccharide antigens on encapsulated bacteria—patients may have recurrent infections with Streptococcus pneumoniae and Haemophilus influenzae despite normal total IgG. IgG3 deficiency is associated with recurrent respiratory infections. Diagnosis requires measuring IgG subclasses and assessing functional antibody responses to polysaccharide vaccines. Treatment depends on severity and may include immunoglobulin replacement in severe cases.
IgG4-related disease (IgG4-RD) is a systemic fibro-inflammatory condition characterized by tumefactive (mass-forming) lesions, lymphoplasmacytic infiltration rich in IgG4-positive plasma cells, and storiform fibrosis. It can affect virtually any organ, most commonly the pancreas (autoimmune pancreatitis), salivary glands, lacrimal glands, retroperitoneum, and kidneys. Serum IgG4 is elevated in about 60–70% of cases but is neither required for nor specific to the diagnosis. Tissue biopsy remains the gold standard. IgG4-RD responds well to corticosteroids initially, but relapse is common, and steroid-sparing agents like rituximab are increasingly used.
IgG crosses the placenta through an active transport mechanism mediated by the neonatal Fc receptor (FcRn) on placental cells. This receptor specifically binds the Fc region of IgG molecules and transfers them from maternal to fetal circulation, with transfer increasing throughout pregnancy and peaking in the third trimester. This provides the newborn with passive immunity against pathogens the mother has encountered or been vaccinated against. The other immunoglobulin classes (IgM, IgA, IgD, IgE) are either too large or lack the specific Fc structure needed for FcRn binding. Maternal IgG gradually wanes in the infant over 3–6 months as the baby begins producing its own antibodies.

Related Biomarkers

IgMImmunoglobulin MIgAImmunoglobulin AWBCWhite Blood CellsALBAlbuminTPTotal Protein

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Medical Disclaimer: This information is for educational purposes only and is not a substitute for professional medical advice, diagnosis, or treatment. Reference ranges may vary between laboratories. Always consult your healthcare provider for interpretation of your specific test results.

Disclaimer: SymptomGPT is not a medical diagnosis tool and does not provide medical advice. Always consult a qualified healthcare professional. If you are experiencing a medical emergency, call 911 immediately.