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Reference Guide
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Globulin is the second most abundant type of protein in the blood, with significant implications for overall health.

Globulin is a diverse group of proteins found in the blood plasma and bodily fluids. It encompasses various types, including alpha, beta, and gamma globulins, each with distinct roles and characteristics.

Globulins play essential roles in the immune system, blood clotting, and transporting substances throughout the body. They act as antibodies, fighting off infections and pathogens, and contribute to the body's defense against foreign invaders. Additionally, globulins are involved in maintaining proper blood viscosity and aiding in the clotting process when injuries occur.

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: [4.] 

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.

Laboratory Testing for Globulin Protein

Blood Tests

Blood tests are the primary method used to measure globulin levels in the body. During a blood test, a healthcare professional collects a sample of blood, typically through venipuncture, from a vein in the arm.

Assessment of total globulin protein levels is part of routine blood work called a comprehensive metabolic panel.  In some cases, more specialized testing called electrophoresis may be warranted to assess the amount of alpha, beta and gamma globulins in the blood or urine.   

The blood sample is then sent to a laboratory for analysis, where globulin levels are measured, often via serum electrophoresis.  

The serum protein electrophoresis (SPEP) test is utilized to detect certain diseases by measuring specific proteins in the blood.  Through serum protein electrophoresis, proteins in the blood serum are separated into groups based on their size, shape, and charge. 

Urine Tests

Urine electrophoresis testing may also be performed, often to look for the presence of a protein known as the Bence-Jones protein as part of myeloma screening.  [6.]

Preparation for Lab Testing

Fasting is often required prior to blood draws for globulin testing.  

Interpreting Globulin Test Results

Reference Range for Globulin Levels

It is important to consult with the laboratory company used to interpret test results.  Common reference ranges for adult globulin levels in blood are:  [8.]

Globulin - 2.3-3.4 g/dL 

Clinical Significance of High Globulin Levels

Elevations in total globulin levels may require followup testing to determine the type of globulin elevated.  Elevations are typically due to elevations in gamma globulins.  [2.] 

Potential causes of elevated globulins include:  [2., 3., 5., 7.]


  • Causes: Inflammatory states such as infections or autoimmune diseases, and pregnancy.
  • Relation to High Globulin Levels: Inflammatory processes trigger the liver to produce more alpha-1 globulins, leading to elevated levels detected in blood tests. Pregnancy can also result in increased alpha-1 globulins due to physiological changes in protein metabolism.


  • Causes: Inflammatory states, nephrotic syndrome, oral contraceptive use, steroid use, and hyperthyroidism. 
  • Relation to High Globulin Levels: Similar to alpha-1, inflammatory conditions stimulate the liver to produce more alpha-2 globulins. Nephrotic syndrome, oral contraceptives, steroids, and hyperthyroidism can also lead to increased production or altered metabolism of alpha-2 globulins.


  • Causes: Hyperlipidemia and iron-deficiency anemia.
  • Relation to High Globulin Levels: Beta globulins such as transferrin (involved in iron transport) and components of lipoproteins (e.g., LDL and VLDL) can be elevated in conditions like hyperlipidemia and iron-deficiency anemia due to increased production or altered metabolism.


  • Causes: Polyclonal and Monoclonal Gammopathies.
  • Relation to High Globulin Levels: Polyclonal gammopathies involve the overproduction of various types of immunoglobulins, leading to increased gamma globulins. Monoclonal gammopathies, such as multiple myeloma, result in the overproduction of a single clone of plasma cells, leading to elevated levels of a specific type of immunoglobulin and hence gamma globulins.

Clinical Significance of Low Globulin Levels

As is the case with high globulin levels, the finding of low total globulin levels may require additional assessment.  Common causes of low globulin levels include:  [2., 7.]

Liver Disease: Conditions affecting liver function, such as cirrhosis or hepatitis, can lead to decreased globulin synthesis, resulting in low globulin levels.

Malnutrition: Inadequate protein intake or malabsorption disorders can lead to overall protein deficiency, including globulins, resulting in low levels.

Nephrotic Syndrome: Excessive loss of proteins, including globulins, through the kidneys in nephrotic syndrome can lead to low levels.

Immunodeficiency Disorders: Primary immunodeficiency disorders or conditions that suppress the immune system can result in reduced production of globulins, particularly immunoglobulins.

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Globulin is a group of proteins found in your blood, made by your liver and immune system. These proteins have many important jobs, such as carrying hormones, minerals, and vitamins throughout your body, helping your immune system by creating antibodies, and assisting in blood clotting. In simple terms, globulins are like the body's support team, making sure essential substances reach their destinations while also protecting against infections. They play a crucial role in keeping you healthy and feeling good.
If Your Levels Are High
Elevated globulin levels might mean that your body is working hard to fight off an infection, deal with inflammation, or handle other challenges to your immune system. Your liver could also be putting in extra effort to produce these proteins. Some medications, like birth control pills or steroids, might contribute to higher globulin levels too. Additionally, long-term health issues such as liver disease, kidney disease, or autoimmune disorders could be playing a role. Keep in mind that these are just possible reasons for increased globulin levels and not definite conclusions.
Symptoms of High Levels
Symptoms of high levels of Globulin could include fatigue, loss of appetite, weight loss, and swelling in your ankles or abdomen. In some cases, there may be no noticeable symptoms at all.
If Your Levels are Low
Low globulin levels might mean that your body isn't getting enough protein or has trouble absorbing it. This could be due to issues with your liver, which is responsible for making these proteins, or it might be a sign of a weak immune system. Some specific conditions that could lead to low globulin levels include malnutrition and liver disease. Additionally, certain medications, like birth control pills or hormone treatments, could also affect your globulin levels. In short, low globulin levels could point to a variety of factors affecting your body's protein production or absorption, and it's essential to consider these possibilities when interpreting your results.
Symptoms of Low Levels
Symptoms of low levels of Globulin may not be immediately noticeable, but could include frequent infections, unexplained weight loss, fatigue, and muscle weakness.
See References

[1.] Aguilera G. Stress, Angiotensin, and Cognate Receptors. Stress: Neuroendocrinology and Neurobiology. Published online 2017:243-255. doi: 

[2.] Busher JT. Serum Albumin and Globulin. In: Walker HK, Hall WD, Hurst JW, editors. Clinical Methods: The History, Physical, and Laboratory Examinations. 3rd edition. Boston: Butterworths; 1990. Chapter 101. Available from: 

[3.] Globulins. Elsevier eBooks. Published online January 1, 2013:618-619. doi: 

[4.] Harris DJ. Clinical tests. Handbook of Avian Medicine. Published online 2009:77-84. doi:

[5.] Hashash JG, Koutroumpakis F, Anderson AM, Rivers CR, Hosni M, Koutroubakis IE, Ahsan M, Gkiaouraki E, Dunn MA, Schwartz M, Barrie A, Babichenko D, Tang G, Binion DG. Elevated serum globulin fraction as a biomarker of multiyear disease severity in inflammatory bowel disease. Ann Gastroenterol. 2022 Nov-Dec;35(6):609-617. doi: 10.20524/aog.2022.0748. Epub 2022 Oct 3. PMID: 36406970; PMCID: PMC9648529.

[6.] Jenkins MA. Serum and urine electrophoresis for detection and identification of monoclonal proteins. Clin Biochem Rev. 2009 Aug;30(3):119-22. PMID: 19841694; PMCID: PMC2755000.

[7.] O’connell TX, Horita TJ, Kasravi B. Understanding and Interpreting Serum Protein Electrophoresis. American Family Physician. 2005;71(1):105-112. 

[8.] Pagana KD, Pagana TJ, Pagana TN. Mosby’s Diagnostic & Laboratory Test Reference. 14th ed. St. Louis, Mo: Elsevier; 2019.

[9.] Serum Protein Electrophoresis: Reference Range, Interpretation, Collection and Panels. eMedicine. Published online August 11, 2021. 

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