Alpha-2-macroglobulin

Why this test?

• Diagnosis of the risk of liver fibrosis in patients with chronic liver disease;
• Diagnosis of liver fibrosis in patients with chronic liver disease;
• Diagnosis of nephrotic syndrome: alpha-2-macroglobulin levels increase in proportion to the severity of the process, which is expressed by the loss of protein in the urine.

In what cases is it prescribed?

• In the examination of patients with chronic liver diseases, to assess the risk of fibrosis and cirrhosis;
• In the examination of patients with nephrotic syndrome;
• In the examination of patients with kidney tumors, benign prostatic hyperplasia, prostate carcinoma;
• In case of diabetes  of long duration.

Test information

Human alpha-2-macroglobulin (A2M) is a 720 kDa high molecular weight plasma glycoprotein with a tetrameric structure and a large number of disulfide bonds. It is the largest non-globulin protein, one of the main components of the alpha-2-globulin fraction and has many different functions. In particular, it is involved in the inhibition of various types of nonspecific plasma proteinases, transport of cytokines, growth factors, hormones, in the development of immune and inflammatory reactions, and has immunosuppressive properties. Also A2M is involved in the mechanisms of inhibition of enzyme cascades in the complement system, kallikrein-kinin system, blood coagulation system and fibrinolysis.

A2M synthesis occurs in liver cells, from where it enters the blood, where it circulates and practically does not diffuse into other fluids due to its large size. Significant increases in A2M levels are observed during embryogenesis, during pregnancy, in children, as well as in all periods of human life characterized by active growth, development and differentiation. It should be noted that A2M is an estrogen-dependent protein, so its average level is slightly increased in women of reproductive age compared to men. In children, its level is on average twice as high as in adults and decreases to adult levels in adolescence.

Serum A2M levels are an important diagnostic marker of liver fibrosis resulting from chronic liver diseases. These include viral hepatitis B and C, non-alcoholic fatty disease, alcoholic liver damage, and, as a result, the formation of cirrhosis. It is important to note that A2M levels reflect the activity of liver fibrosis, which is important in determining the stage of the disease, as well as in the appointment of pathogenetic therapy. The "golden" standard for the diagnosis of liver fibrosis is a liver biopsy followed by morphological examination of the biopsy. This procedure is highly informative, but has a number of drawbacks: the possibility of false negative results, invasiveness of the method and the development of complications after the procedure. Therefore, the determination of A2M along with other biochemical parameters of liver damage can be recommended as an informative, non-invasive way to assess the degree of liver fibrosis activity.

Elevated levels of A2M are also noted in the long-term course of diabetes mellitus, nephrotic syndrome. In nephrotic syndrome, an increase in A2M levels occurs due to a decrease in plasma volume, a decrease in plasma oncotic pressure due to the loss of lower molecular weight proteins in the urine and a slight excretion of A2M itself in the urine. It should also be noted that A2M is produced by the cells of the prostate gland, which leads to the possibility of increasing its values in benign prostatic hyperplasia and decreasing in prolonged active cancer process in this organ.

Decrease of A2M level is noted in acute pancreatitis, after operations accompanied by massive blood loss, in septicemia. Patients who have had an acute myocardial infarction with low A2M levels have a statistically more favorable prognosis after survival of more than one year.

When determining protein fractions in serum protein electrophoresis, an increase in the alpha2-fraction, which includes A2M, should be noted. One of the modern and highly sensitive methods for the diagnosis of serum proteins is the immunoturbidimetric method. It allows to determine the protein concentration with the change in turbidity of the solution as a result of the antigen-antibody reaction and is used when it is impossible to determine the protein content by its enzymatic activity.