Serum proteins represent a diverse microenvironment. They are a source of nutrition and a buffer system. Immunoglobulins and related proteins function as immunologic agents. Carrier proteins (e.g., haptoglobin, prealbumin, transferrin) transport certain ions and molecules to their destinations. Antiproteases (e.g., alpha1-antitrypsin [AAT], alpha2-macroglobulin) regulate the activity of various proteolytic enzymes, and other classes of proteins regulate oncotic pressure, genetic component pressures (e.g., chromosomal), and metabolic substances (e.g., hormones).
Blood serum and urine are commonly screened for the monoclonal immunoglobulin component by means of SPEP. Immunoglobulins are the major component of the serum gamma-globulin fraction. In health, the immunoglobulins are polyclonal instead of monoclonal. When a monoclonal band is observed, it frequently signals a neoplastic process such as multiple myeloma or Waldenström macroglobulinemia. SPEP enhances follow-up procedures such as specific protein quantification of immunoglobulins (IgA, IgG, IgM) and immunofixation. It provides one of the best tools for general screening of the human health state.
These tests can diagnose some inflammatory and neoplastic states, nephrotic syndromes, liver disease, and immune dysfunctions and can evaluate nutritional states and osmotic pressures in edematous and malnourished patients. SPEP produces electrophoretic separation of the five major protein fractions (albumin, alpha1-globulin, alpha2-globulin, beta-globulin, and gamma-globulin) in serum and urine specimens so that a more definitive diagnosis can be made. Major components present in each protein fraction or zone exhibit characteristic, unique electrophoretic patterns and are defined as the albumin zone (albumin); the alpha1 zone (alpha1-lipoproteins, high-density lipoprotein, AAT); the alpha2 zone (alpha2-macroglobulin, haptoglobin, beta-lipoprotein); the beta zone (transferrin, C3 [complement]); and the gamma zone (fibrinogen, IgA, IgM, IgG).
Serum Protein Electrophoresis
| Total Protein | SI Units | Albumin | SI Units |
|---|
| Adult: 6.0–8.0 g/dL | 60–80 g/L | Adult: 3.8–5.0 g/dL | 38–50 g/L |
| <5 d: 5.4–7.0 g/dL | 54–70 g/L | Newborn: 2.6–3.6 g/dL | 26–36 g/L |
| 1–3 yr: 5.9–7.0 g/dL | 59–70 g/L | 1–3 yr: 3.4–4.2 g/dL | 34–42 g/L |
| 4–6 yr: 5.9–7.8 g/dL | 59–78 g/L | 4–6 yr: 3.5–5.2 g/dL | 35–52 g/L |
| 7–9 yr: 6.2–8.1 g/dL | 62–81 g/L | 7–9 yr: 3.7–5.6 g/dL | 37–56 g/L |
| 10–19 yr: 6.3–8.6 g/dL | 63–86 g/L | 10–19 yr: 3.7–5.6 g/dL | 37–56 g/L |
Alpha1-globulin: 0.1–0.3 g/dL
Alpha2-globulin: 0.6–1.0 g/dL
Beta-globulin: 0.7–1.4 g/dL
Gamma-globulin: 0.7–1.6 g/dL
Urine Protein Electrophoresis
A descriptive report is prepared by the pathologist.
Clinical Alert
Normally, very little protein is excreted in the urine; however, relatively large amounts may be excreted in certain disease states. In the presence of lipoid nephrosis, selective proteinuria produces excess albumin excretion. With nonselective proteinuria (e.g., glomerulonephritis), all types of serum proteins usually appear in the urine. Urine protein electrophoresis (UPEP) can identify Bence Jones proteins, which migrate in the beta-globulin and gamma-globulin regions. See Chapter 3 for a complete explanation of urine protein and albumin
The following are the most frequent protein abnormalities in protein quantification and SPEP:
Total serum protein (the sum of circulating serum proteins) increases (hyperproteinemia) with dehydration and hemoconcentration states because of fluid loss (e.g., vomiting, diarrhea, poor kidney function). Increases are also found with the following conditions:
Liver disease
Multiple myeloma and other gammopathies
Waldenström macroglobulinemia
Tropical disease
Sarcoidosis and other granulomatous diseases
Collagen disorders such as systemic lupus erythematosus (SLE) and RA
Chronic inflammatory states
Chronic infections
Total serum protein decreases (hypoproteinemia) with the following conditions:
Insufficient nutritional intake (starvation or malabsorption)
Severe liver disease or alcoholism
Kidney disease, nephrotic syndrome
Diarrhea (Crohn disease, ulcerative colitis)
Severe skin diseases or burns
Severe hemorrhage (when plasma volume is replaced more rapidly than protein)
Heart failure
Hypothyroidism
Prolonged immobilization (trauma, orthopedic surgery)
Serum albumin increases with IV infusions and dehydration (elevated hemoglobin and hematocrit indicate higher albumin levels).
Serum albumin decreases with the following conditions:
Decreased synthesis states such as liver disease, alcoholism, malabsorption syndromes,
Crohn disease, other protein-losing enteropathies, starvation states, and congenital analbuminemia
Increased albumin loss (e.g., nephrotic syndrome, third-degree burns)
Poor nutrition states and inadequate iron intake
Low albumin-to-globulin ratio (e.g., collagen disease, chronic inflammation, liver diseases, macroglobulinemia, severe infections, cachexia, burns, ulcerative colitis)
Alpha1-globulin increases with infection (acute and chronic) and febrile reactions.
Alpha1-globulin decreases with nephrosis and AAT deficiency.
Alpha2-globulin increases with the following conditions:
Biliary cirrhosis
Obstructive jaundice
Nephrosis
Multiple myeloma (rare)
Ulcerative colitis
Alpha2-globulin decreases with acute hemolytic anemia.
Beta-globulin increases with biliary cirrhosis, obstructive jaundice, and multiple myeloma
(occasional).
Beta-globulin decreases with nephrosis.
Gamma-globulin increases with the following conditions:
Chronic infections
Hepatic diseases
Autoimmune diseases
Collagen diseases
Multiple myeloma
Waldenström macroglobulinemia
Leukemia and other cancers
Gamma-globulin decreases with the following conditions:
Agammaglobulinemia
Hypogammaglobulinemia
Nephrotic syndrome