What is globulin?
Globulin is a protein and is made in the liver. High levels may indicate autoimmune disease, infections or cancer. A low globulin reading may be a sign of liver or kidney disease.
About 40% of the proteins in your blood are alpha, beta and gamma globulins. Albumin is the other common blood protein.
Globulin forms the main transport system for various substances as well as a constituant of the antibody system (“immunoglobulins”) that fights infections and viruses. Globulins are also needed to form blood clots and keep the liver and kidneys functioning.
The globulin value on the chemistry panel is not measured, but is calculated by the equation: Globulins = Total protein – Albumin.
There are four groups of globulins. Serum protein electrophoresis is the test used to distinguish one from another and establish levels of each within the bloodstream.
Alpha 1 globulins:
- Mainly alpha-1 antitrypsin.
Alpha 2 globulins:
- Alpha 2 macroglobulin.
- Haptoglobin.
Beta globulins:
- Transferrin.
- Complement components C3, C4, C5.
Gamma globulins:
Mostly immunoglobulins (antibodies)
- IgG: majority of the immunoglobulin component. Many antibodies to bacteria and viruses are IgG.
- IgE: involved in allergic response. Triggers histamine release. Also protects against parasites.
- IgM: largest antibodies and first type produced in response to infection.
- IgD: exists in very small quantities in blood. Function not very well understood.
- IgA: found in mucous membranes, blood, saliva and tears. Protect body surfaces which are exposed to foreign substances.
Why test proteins in blood (serum)?
Hundreds of proteins are dissolved in the plasma. By measuring the concentration of these proteins, the clinician can obtain information regarding disease states in different organ systems. The measurement of protein is done on serum, which is the fluid that remains after plasma has clotted, thus removing fibrinogen and most of the clotting factors. Total protein content provides some information regarding a patient's general status; more clinically useful data are obtained from fractionating the total protein. The normal serum protein level is 6 to 8 g/dl. Albumin makes up 3.5 to 5.0 g/dl, and the remainder is the total globulins. These values may vary according to the individual laboratory.
Proteins are vital to the functioning of virtually all parts of the body. The most common protein in the blood is albumin, which prevents fluid from leaking and carrying substances through the body.
Almost all of the other proteins in the blood are globulins, formed by the immune system and by the liver. There are several kinds of globulins, but a basic total protein test usually will not measure the amounts of each specific type.
A blood test of total proteins will often directly measure albumin. This allows for calculating the number of globulins by subtracting albumin from total protein. It also allows for a calculation of the A/G ratio.
When is a globulin test ordered?
A globulin test is ordered as part of a routine physical exam (“Complete Metabolic Panel”) to identify potential liver and kidney problems or to monitor disease progression.
A globulin test may be part of liver function tests, metabolic panel, total protein test or serum protein electrophoresis.
Your healthcare provider may order tests to see how your liver is working if you have symptoms such as:
Globulin tests can be used to help diagnose a variety of conditions, including:
Globulin proteins are important to liver and kidney function. A total protein test is a good indication of how the liver is working. Low total protein levels can be a sign of liver disease. While globulin blood tests can help a healthcare provider to make a diagnosis, they will also use other tests and evaluations to diagnose a specific condition or illness.
What is the normal range for a globulin test?
Protein globulin levels for adults normally fall between 1.5 - 4.5 g/dL. The normal range for total protein is between 6.4 and 8.3 g/dL.
If the results are normal, you won't need any specific follow-up for the test. However, your healthcare provider may want to run other types of tests if you are having symptoms.
If the results are outside the normal range, your healthcare provider may have you do additional blood tests to provide more specific information. Or, you may need imaging tests like an MRI to look for tumors or swollen lymph nodes if cancer is suspected.
What is the A/G ratio?
A total protein test also shows the ratio of albumin to globulin or A/G ratio. The A/G ratio is a measure of the amount of albumin proteins in blood compared to globulins. Typically, your body has slightly more albumin than globulins. A normal A/G ratio is slightly more than 1.
References:
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: https://www.ncbi.nlm.nih.gov/books/NBK204/
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.
Jolles S, Borrell R, Zouwail S, Heaps A, Sharp H, Moody M, Selwood C, Williams P, Phillips C, Hood K, Holding S, El Shanawany T. Calculated globulin (CG) as a screening test for antibody deficiency. Clin Exp Immunol. 2014 Sep;177(3):671-8. doi: 10.1111/cei.12369. PMID: 24784320; PMCID: PMC4137851.
Links:
- https://www.cancer.org/cancer/types/multiple-myeloma/about/what-is-multiple-myeloma.html
- Loh RK, Vale S, McLean-Tooke A; Quantitative serum immunoglobulin tests. Aust Fam Physician. 2013 Apr42(4):195-8.
- Bird JM; Investigating an incidental finding of a paraprotein. BMJ. 2012 May 4344:e3033. doi: 10.1136/bmj.e3033.
- Immunoglobulin; Public Health England
- Busher JT; Serum Albumin and Globulin
- Serum globulin electrophoresis; MedlinePlus
- Monoclonal gammopathy of undetermined significance (MGUS); Melbourne Haematology
- Immunoelectrophoresis - blood; MedlinePlus
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High globulin levels may be a sign of:
Abnormal results may also be caused by certain medicines, dehydration, pregnancy, or other conditions.
Any increase or decrease in the globulin fraction should be evaluated by serum electrophoresis. The pattern should be visually inspected for abnormalities in particular regions.
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→ Malnutrition (a lack of protein in the diet can cause low globulin levels),
→ Congenital immune deficiency (aka congenital immunodeficiency or primary immunodeficiency is a genetic defect that prevents children from producing enough immune cells or substances to help protect the body against infections.)
→ Chronic inflammation (can affect the production and distribution of globulin in the body)
→ Liver disease (liver produces many of the proteins in the body, including globulin. Certain liver diseases, such as cirrhosis, can impair the liver's ability to produce globulin.)
→ Kidney (kidneys help regulate the balance of proteins in the body. If the kidneys are not functioning properly, it can result in low globulin levels.)
→ Nephrotic syndrome (a kidney disorder that causes your body to pass too much protein in your urine)
→ Autoimmune disorders (such as lupus and rheumatoid arthritis)
→ Genetic disorders (genetic disorders, such as X-linked agammaglobulinemia, can cause low levels of globulin.)
Any increase or decrease in the globulin fraction should be evaluated by serum electrophoresis. The pattern should be visually inspected for abnormalities in particular regions.
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Alanine-aminotransferase (ALT, SGPT), Albumin, Serum, Albumin/Globulin (A/G) Ratio, Alkaline Phosphatase (ALP), Aspartate-aminotransferase (AST, SGOT), Bilirubin Total, Blood urea nitrogen (BUN), BUN/Creatinine Ratio, Calcium, Serum, Carbon Dioxide (CO2), Chloride, Serum, Creatinine, Serum, eGFR - Estimated Glomerular Filtration Rate (African Am), eGFR - Estimated Glomerular Filtration Rate (Non-African Am), eGFR / Cystatin C, Globulin, Serum (aka Globulin, Total), Glucose, Glucose Non-Fasting, Intestinal Isoenzymes (Alkaline Phosphatase), Potassium, Serum (Kalium), Sodium, Serum (Natrium), Total Protein, Serum
