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300) The serum protein and immunofixation electrophoresis (IFE) patterns shown in the figure and table were determined for a 55-year-old man with type 1 diabetes. The protein fractions are shown below. Which one of the following represents the best interpretation of these protein patterns?
Protein Fractions Determined by Serum Protein Electrophoresis

Protein Fractions Patient Results, g/dL Reference Range, g/dL

Albumin 2.2 3.6–4.8

Alpha-1 0.5 0.2–0.4

Alpha-2 1.4 0.6–0.9

Beta 0.9 0.6–1.0

Gamma 1.2 0.8–1.8

Total protein 6.2 6.7–8.6

Protein Fractions	Patient Results, g/dL	Reference Range, g/dL
Albumin	2.2	3.6–4.8
Alpha-1	0.5	0.2–0.4
Alpha-2	1.4	0.6–0.9
Beta	0.9	0.6–1.0
Gamma	1.2	0.8–1.8
Total protein	6.2	6.7–8.6

This is the serum protein electrophoresis (SPEP) pattern that is seen in severe liver disease. This is the serum IFE pattern for a monoclonal protein. This is the SPEP pattern that is usually seen in nephrosis. This is the SPEP pattern that is seen in iron deficiency anemia. This is the SPEP pattern that is seen in alpha-1 antitrypsin deficiency.

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• The major proteins found in the alpha-2 region of the serum protein electrophoresis (SPEP) pattern are alpha-2-macroglobulin and haptoglobin. Ceruloplasmin, antithrombin III, and fibronectin are present at low concentrations and do not significantly contribute to the protein pattern.

• The elevated protein band in the alpha-2 region is most likely due to alpha-2-macroglobulin.

• Alpha-2-macroglobulin is a large protein with a molecular weight of 725 kDa that is not excreted into the urine. Alpha-2-macroglobulin is a protease inhibitor.

• A SPEP pattern with a low albumin, elevated alpha-2 globulin, a normal or decreased gamma globulin fraction, and a low total protein concentration is usually indicative of nephrosis.

• In nephrosis, albumin and other low molecular weight proteins are excreted into the urine and the hepatic synthesis of alpha-2-macroglobulin is increased to compensate for the decreased oncotic pressure. As a result, high levels of alpha-2-macroglobulin are observed in nephrosis.

• Although a monoclonal protein can be detected in the alpha-2 region, it is a rare occurrence.

Tate J, Caldwell G, Daly J, et al: Recommendations for standardized reporting of protein electrophoresis in Australia and New Zealand. Ann Clin Biochem 2012;49:242–256.

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Clinical Pathology: General Principles, Clinical Chemistry

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