Alpha-2-Macroglobulin (A2M) is a major plasma protein in humans with various functions including ion transport, carrier protein, and the inhibition of proteinases.
It transports hormones and enzymes, exhibits effector and inhibitor functions in the development of the lymphatic system, and inhibits components of the complement system and hemostasis system.
Elevated levels are seen in clinical conditions such as cirrhosis (=scarring of the liver), nephrotic syndrome (=a group of symptoms that indicate your kidneys are not working properly), severe burns and diabetes.
Decreased levels are seen in pancreatitis (=inflammation of the pancreas), fibrinolysis (=prevents blood clots that occur naturally from growing and causing problems), and liver disease.
Vandooren J, Itoh Y. Alpha-2-Macroglobulin in Inflammation, Immunity and Infections. Front Immunol. 2021 Dec 14;12:803244. doi: 10.3389/fimmu.2021.803244. PMID: 34970276; PMCID: PMC8712716.
Shimomura R, Nezu T, Hosomi N, Aoki S, Sugimoto T, Kinoshita N, Araki M, Takahashi T, Maruyama H, Matsumoto M. Alpha-2-macroglobulin as a Promising Biological Marker of Endothelial Function. J Atheroscler Thromb. 2018 Apr 1;25(4):350-358. doi: 10.5551/jat.41335. Epub 2017 Nov 1. PMID: 29093276; PMCID: PMC5906188.
Patients with acute pancreatitis exhibit low serum concentrations, which correlate with the severity of the disease. In hyperfibrinolytic states, after major surgery, in septicemia, and severe hepatic insufficiency, the measured levels of alpha-2-macroglobulin are often low. Acute myocardial infarction patients with low alpha-2-macroglobulin have been reported to have a significantly better prognosis with regard to the greater than a year survival time.
Increased levels of alpha-2-macroglobulin are found in nephrotic syndrome when lower molecular weight proteins are lost, but alpha-2-macroglobulin is retained because of its large size.
What is nephrotic syndrome?
Nephrotic syndrome is a group of symptoms that indicate your kidneys are not working properly.
These symptoms include:
- too much protein in your urine, called proteinuria
- low levels of a protein called albumin in your blood, called hypoalbuminemia
- swelling in parts of your body, called edema
- high levels of cholesterol and other lipids (fats) in your blood, called hyperlipidemia
Your kidneys are made up of about a million filtering units called nephrons. Each nephron includes a filter, called the glomerulus, and a tubule. The glomerulus filters your blood, and the tubule returns needed substances to your blood and removes wastes and extra water, which become urine. Nephrotic syndrome usually happens when the glomeruli are inflamed, allowing too much protein to leak from your blood into your urine.
In patients with liver cirrhosis and diabetes, the levels of alpha-2-macroglobulin are also found to be elevated.
Cirrhosis is scarring (fibrosis) of the liver caused by long-term liver damage. The scar tissue prevents the liver working properly. Cirrhosis is sometimes called end-stage liver disease because it happens after other stages of damage from conditions that affect the liver, such as hepatitis.
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