Globulins IgG

Globulin proteins, particularly Immunoglobulin G (IgG), play essential roles in the immune system by protecting the body against infections.  

IgG is the most abundant antibody in human blood and is crucial for long-term immunity.  It is produced by B cells and is involved in various immune functions such as neutralizing pathogens, activating complement, and facilitating phagocytosis. 

There are four IgG subclasses—IgG1, IgG2, IgG3, and IgG4—each with distinct roles and functions in the immune response. 

Assessing IgG levels through blood tests is crucial for diagnosing and managing conditions associated with high or low levels of IgG, ensuring appropriate treatment and monitoring.

Definition and Function of Globulin

What are Globulin Proteins, and What Do They Do in the Body?

Globulin proteins represent a diverse group of proteins found in the blood plasma and bodily fluids, playing essential roles in various physiological processes. Globulins are the second most abundant type of protein in the blood in humans, after albumin.  

Comprising several subclasses, including alpha, beta, and gamma globulins, they exhibit diverse structures and functions. 

Globulins are primarily synthesized in the liver and immune cells.  

Globulins are characterized using a laboratory technique called electrophoresis. In this process, a sample of blood plasma or serum is subjected to an electric field, causing the proteins within the sample to migrate based on their charge and size. 

Since globulins have varying charges and molecular weights, they migrate at different rates and form distinct bands on a gel or strip. These bands are then visualized and analyzed to identify and quantify the different types of globulins present in the sample. 

The three types of globulins determined by electrophoresis include:  [8.] 

Alpha Globulins: 

Alpha globulins are a group of plasma proteins that include transport proteins such as alpha-1 antitrypsin, which inhibits enzymes that degrade connective tissue, and haptoglobin, which binds free hemoglobin to prevent oxidative damage. 

Alpha globulins also contain lipoproteins involved in lipid transport, as well as acute-phase proteins like ceruloplasmin, which binds and transports copper ions. 

Overall, alpha globulins contribute to immune function, enzyme regulation, and lipid transport in the body.

Beta Globulins: 

Beta globulins comprise a heterogeneous group of plasma proteins with diverse functions. These proteins include transferrin, responsible for transporting iron ions in the blood, and complement proteins involved in the immune response against pathogens. 

Additionally, beta globulins encompass components of lipoproteins, such as low-density lipoprotein (LDL) and very-low-density lipoprotein (VLDL), which transport cholesterol and triglycerides in the bloodstream. 

Beta globulins play critical roles in iron metabolism, immune defense, and lipid transport, among other functions.

Gamma Globulins: 

Gamma globulins, also known as immunoglobulins or antibodies, are key components of the immune system. 

These proteins are produced by plasma cells in response to specific antigens, functioning to recognize and neutralize pathogens such as bacteria, viruses, and toxins. 

Immunoglobulins consist of various classes, including IgG, IgA, IgM, IgD, and IgE, each with distinct roles in humoral immunity.  

IgG, the most abundant antibody class, provides long-term immunity against pathogens, while IgM serves as the primary antibody during the initial stages of infection. 

IgA plays a crucial role in mucosal immunity, while IgD and IgE are involved in antigen recognition and allergic responses, respectively. 

Gamma globulins are essential for mounting an effective immune response and maintaining immune homeostasis in the body.

What are IgG Globulins? 

IgG antibodies are the most abundant type of antibodies found in human blood.  Made by B cells in the plasma, they play a crucial role in the immune system's humoral response to pathogens and antigens.

IgG Globulin Subclasses  [11., 21.]

There are four IgG subclasses in humans – IgG1, IgG2, IgG3, and IgG4 – named in order of their abundance in serum. IgG1 is the most abundant (66%), followed by IgG2 (23%), IgG3 (7%), and IgG4 (4%).  

These subclasses differ in their ability to activate complement, bind to Fc receptors on phagocytic cells, and cross the placenta.

Each member of the IgG subclasses has distinct roles:

IgG1: Comprising around 65% of total IgG, IgG1 is essential for responding to protein antigens and allergens.  It activates the classical complement pathway and binds effectively to Fc receptors on immune cells.

Along with IgG3, IgG1 is a highly effective immune-stimulating immunoglobulin, with a longer half-life than IgG3. 

IgG2: Important for defending against encapsulated bacteria, IgG2 primarily responds to polysaccharide antigens. Deficiency in IgG2 can lead to increased susceptibility to bacterial infections.

IgG3: Known for its potent pro-inflammatory response, IgG3 has a shorter half-life but is highly effective in effector functions, including complement activation and Fc receptor binding.

IgG3, with its long hinge region, is highly effective in effector functions but has a shorter half-life than IgG1, the other potent inducer of immune responses.  

IgG4: Unique for its ability to undergo "Fab arm exchange," IgG4 can bind two different antigens, reducing immune response severity.  It is involved in responses to long-term antigen exposure, such as allergies and chronic infections.

IgG4 is unique in its ability to block excessive immune responses, such as in allergies and long-term antigen exposure.

IgG Globulin Functions

As a family, the IgG globulins are responsible for several immune functions:  [14., 21.]

Antibody-Dependent Cellular Cytotoxicity (ADCC): IgG antibodies can bind to Fc receptors on immune cells like natural killer cells, triggering the release of cytotoxic granules that can destroy the target cell. 

Antibody-Dependent Cellular Phagocytosis (ADCP): IgG antibodies can bind to Fc receptors on phagocytic cells like macrophages and neutrophils, promoting the phagocytosis and destruction of the antibody-bound infective agent. 

Complement-Mediated Cytotoxicity (CMC): IgG antibodies can activate the classical complement pathway, leading to the formation of the membrane attack complex and lysis of the target cell.

Placental transfer: IgG is the only antibody isotype that can cross the placenta, providing passive immunity to the fetus in utero.  [11.]

Causes and Symptoms of Elevated IgG Globulin Levels

Elevated IgG levels may or may not present symptoms; the symptomatology often depends on the cause and the chronicity of the pathogenesis.  

However, high IgG levels can indicate the presence of an underlying condition or disease that may be associated with various symptoms.  Symptoms related to elevated IgG levels, depending on the cause, may include:  [5.]

Infections  [13.] 

Elevated IgG levels can occur during acute infections or chronic infections, as the body produces more antibodies to fight the infection.  Symptoms may include fever, fatigue, and signs of the specific infection.

Autoimmune Disorders  [17.] 

High IgG levels are seen in some autoimmune disorders like rheumatoid arthritis, lupus, and celiac disease, particularly in those that affect the connective tissue.  [5.]

Symptoms depend on the specific autoimmune condition but may include joint pain, rashes, fatigue, and organ-specific manifestations.

Chronic Liver Diseases  [5.] 

Elevated IgG is associated with chronic liver diseases like cirrhosis.  Symptoms can include jaundice, nausea and vomiting, dark urine and light stool, abdominal swelling, fatigue, and complications of liver dysfunction.  [4.]

Multiple Myeloma and Lymphoproliferative Disorders  [19.]

Significantly elevated IgG levels can occur in conditions like multiple myeloma and monoclonal gammopathy of undetermined significance (MGUS).  

Symptoms may include bone pain, anemia, kidney problems, and hyperviscosity syndrome (confusion, dizziness, bleeding).

Inflammatory Conditions  [17.]

High IgG levels are seen in inflammatory conditions affecting the lungs, gastrointestinal tract, and other organs.  Symptoms depend on the specific condition but may include cough, abdominal pain, diarrhea, and organ-specific issues.

General Symptoms  [23.]

In some cases, very high IgG levels can lead to hyperviscosity syndrome, causing symptoms like headaches, visual disturbances, and neurological deficits due to increased blood thickness.

Causes and Symptoms of Low IgG Globulin

The symptomatology of low IgG globulins includes:  [1., 10.]

• Increased susceptibility to infections, often involving Streptococcus pneumoniae, Haemophilus influenzae type b, and Staphylococcus aureus.
  

• Recurrent sinus, respiratory, ear infections  

• Pneumonia, bronchitis 
  

• Gastrointestinal infections, often with diarrhea
  

• Skin infections such as cellulitis or abscesses
  

• Severe, life-threatening infections (rare) 
  

• Poor response to vaccines like pneumonia, influenza 
  

• In children, can lead to growth/developmental delays 
  

• General symptoms like headaches, cough, fever 
  

Causes of Low IgG levels are considered primary, or inherent causes, or secondary causes.  

They include:  [1., 9., 10.]

Primary Immunodeficiency Disorders (PIDs):

• X-linked agammaglobulinemia (XLA) and autosomal recessive agammaglobulinemia cause profound hypogammaglobulinemia with extremely low/absent B cells 
  

• Common variable immunodeficiency (CVID) leads to deficiencies in IgG, IgA and/or IgM 
  

• Hyper-IgM syndromes (X-linked or autosomal recessive) result in IgG and IgA deficiency 
  

Secondary/Acquired Causes:

• Malnutrition 
  

• Certain medications like chemotherapy, long-term corticosteroids 
  

• Protein-losing conditions like enteropathy, nephropathy 
  

• Cancers affecting B-cells like chronic lymphocytic leukemia, lymphoma, multiple myeloma 
  

• HIV infection 
  

• Aging

Transient causes:

• Transient hypogammaglobulinemia of infancy 
  

Lab Testing for Globulins IgG

Lab Test Information, Sample Collection and Preparation

Quantitative IgG tests may be run to assess total IgG levels if there is concern of elevated or decreased levels of IgG.

Alternatively, IgG levels may also be assessed for past exposure to specific infectious agents, to determine if the patient has already developed immunity against the infectious agent in question.  

Positive IgG testing for specific agents confirms a historical exposure to an infectious agent, and current immunity.  Examples include assessment for infections such as Epstein-Barr virus, Cytomegalovirus, Rubella, Herpes Simplex, Varicella Zoster, and others.  

IgG testing may also be performed after vaccine administration, to confirm conferred immunity against an infectious agent.  

IgG testing is also ordered to assess for food sensitivities, which can develop in the setting of dysbiosis and/or leaky gut.  

IgG levels are assessed in the blood.  A venipuncture is required for sample collection.  

Special preparation is generally not necessary, although it is important to consult with the ordering provider prior to sample collection.  

IgG Testing for Food Sensitivities

IgG 1-4 food sensitivity testing is used to identify delayed immune responses to specific food antigens. [7.]  While IgE-mediated food allergies typically provoke immediate hypersensitivity reactions, IgG-mediated responses are associated with delayed onset reactions, making them challenging to diagnose clinically. 

However, accumulating evidence suggests that IgG antibody testing for food sensitivities may shed light for clinicians.  [6., 18., 22.]  Some studies indicate that IgG-mediated immune responses might contribute to the pathogenesis of gastrointestinal inflammation.  [7., 20.] 

By detecting IgG antibodies to specific food antigens,IgG food sensitivity testing aims to identify potential triggers for immune-mediated reactions and provide insights into personalized dietary modifications to alleviate symptoms and improve overall health outcomes.

IgG4, a subtype of immunoglobulin G antibodies, plays a crucial role in modulating immune responses, particularly in the context of allergies. 

Interpretation of Globulins IgG Test Results

Optimal Levels of IgG Globulins

Levels of IgG globulins should be assessed within the context of an individual’s medical history and symptom picture. 

Optimal quantitative IgG levels given by one laboratory company include: [24.] 

Males, by Age:  (mg/dL) 

0 to 10 days: 496−1231

11 days–6 months: 175−639

7–11 months: 261−791

1–3 years: 428–1028

4–6 years: 538–1216

7–9 years: 580–1302

10–11 years: 601–1351

12–13 years: 610–1367

14–15 years: 630–1392

16–19 years: 671–1456 

>19 years: 603–1613

Females, by Age: (mg/dL)

0 to 10 days: 496−1231

11 days–6 months: 184–697

7–11 months: 295–787

1–3 years: 451–1071

4–6 years: 583–1262

7–9 years: 630–1350

10–11 years: 646–1407

12–13 years: 692–1433

14–15 years: 717–1463

16–19 years: 719–1475 

>19 years: 586–1602

Clinical Significance of Elevated Globulins IgG 

Elevated serum Globulins IgG levels may indicate the following: 

• Indication of an active infection or inflammatory condition

• Elevated IgG levels can occur during acute or chronic infections as the body produces more antibodies to fight the infection

• An autoimmune disorder 

• High IgG levels, including autoantibodies, are seen in autoimmune conditions like rheumatoid arthritis, lupus, and others

• Certain cancers, especially multiple myeloma  

• Significantly elevated monoclonal IgG levels can occur in plasma cell disorders like multiple myeloma

• Persistent IgG elevation may indicate the need to investigate B-cell lymphomas

• Marker of chronic liver diseases 

• Elevated IgG is associated with chronic liver diseases like cirrhosis

• Potential sign of inflammatory bowel diseases 

• High IgG levels may be seen in inflammatory conditions affecting the gastrointestinal tract

• Indication of chronic infections like HIV, hepatitis B/C 

• Elevated IgG can occur in chronic viral infections

• Associated with hyperviscosity syndrome some text
  • Very high IgG levels can lead to hyperviscosity syndrome with symptoms like headaches, visual disturbances, and neurological deficits.

• Marker of recent infection or vaccination response 

• IgG levels can be temporarily elevated after an infection or vaccination as part of the immune response, before returning to normal.

• Positive IgG tests against a specific antigen indicates a recent or past exposure to that antigen, conferring immunity.  

Clinical Significance of Decreased IgG Globulin

Decreased serum IgG levels can be observed in immunodeficiency disorders, such as common variable immunodeficiency (CVID) or X-linked agammaglobulinemia (XLA).

It may also indicate a secondary cause of low IgG, including malnutrition or a protein-losing enteropathy, use of certain medications, chronic infections such as HIV, some cancers, or aging.  

IgG Globulin Related Biomarkers to Test

While Globulins IgG is a valuable biomarker, evaluating other related biomarkers in conjunction can provide a more comprehensive understanding of the immune system and disease processes. 

Immunoglobulin A (IgA)

Immunoglobulin A (IgA) is the predominant antibody class found in mucosal secretions and plays a crucial role in mucosal immunity.  

Measuring IgA levels, particularly secretory IgA, can provide insights into mucosal immune function and complement the information obtained from IgG testing. 

Elevated IgA levels may indicate an ongoing mucosal immune response or certain autoimmune disorders, while decreased levels may suggest an increased susceptibility to mucosal infections.

Immunoglobulin M (IgM)

Immunoglobulin M (IgM) is the first antibody produced in response to an antigen and is primarily found in serum. 

IgM levels can be useful in assessing recent or acute immune responses, as well as certain autoimmune conditions like systemic lupus erythematosus (SLE). 

Elevated IgM levels may indicate an ongoing immune response, while decreased levels may suggest immunodeficiency.

Complement Proteins

The complement system is a crucial component of the innate immune system, and measuring complement protein levels, such as C3 and C4, can provide valuable information about complement activation and immune dysregulation. 

Abnormal complement levels may be associated with various autoimmune disorders, infections, or inflammatory conditions.

Order IgG Globulin Testing

Click here to compare testing options and order tests for IgG globulin levels.