Serum protein electrophoresis (SPE) is used to identify patterns in serum proteins associated with inflammation, congenital protein disorders, liver or kidney failure, and malignancies such as multiple myeloma.
SPE separates proteins based on size and electrical charge. The main fractions measured are albumin and globulins, including alpha-1, alpha-2, beta- and gamma-globulins. The relative and absolute quantity of proteins can be further determined using immunofluorescence and immunofixation (Vavricka 2009)
Albumin makes up approximately 60% of total serum protein and can decrease when liver synthesis is compromised, though this decrease takes time to recognize due to albumin’s 12-18 day half-life (Pagana 2022). SPE can detect an albumin decrease of 30% or more. Such a decline may be due to inflammation, malnutrition, liver failure, renal losses, burns, pregnancy, or hormone therapy (Vavricka 2009).
The following information can help clinicians evaluate clients with alterations in their serum protein levels:
Albumin, prealbumin
Alpha1 Globulins:
Alpha2 Globulins:
Beta1 Globulins:
Beta2 Globulins:
Gamma Globulins (primarily IgG):
Note: The gamma fraction is primarily made up of IgG immunoglobulins. Although most IgA, IgM, IgD, and IgE fall within the gamma fraction, some can be found in the SPE's beta, beta, and even alpha2 globulin regions.
| Component | Increased | Decreased |
| Albumin | Dehydration | Burns Cachexia, wasting disease Chronic infection Hemorrhage Impaired liver function Inflammation Malnutrition Nephrotic syndrome Pregnancy Protein-losing enteropathies |
| Alpha1 Globulins | Pregnancy | Alpha1 antitrypsin deficiency |
| Alpha2 Globulins | Adrenal insufficiency Adrenocorticosteroid therapy Advanced diabetes mellitus Nephritic syndrome |
Anemia, megaloblastic Malnutrition |
| Beta Globulins | Biliary cirrhosis Cancer (sometimes) Cushing’s disease Diabetes mellitus (sometimes) Hypothyroidism Iron deficiency anemia Malignant hypertension Nephrosis Polyarteritis nodosa Obstructive jaundice Pregnancy, 3rd trimester |
Protein malnutrition |
| Gamma Globulins | Amyloidosis Chronic infections (granulomatous disease) Chronic lymphocytic leukemia Cirrhosis Hodgkin’s disease Malignant lymphoma Multiple myeloma Rheumatoid and collagen disease |
Agammaglobulinemia Hypogammaglobulinemia |
| Disorder | SPE Pattern |
| Acute reaction Including infections, necrosis, burns, surgery, stress, MI |
Decreased albumin Increased alpha2 globulins |
| Chronic inflammation | Decreased albumin Increased gamma Normal alpha2 |
| Nephrotic syndrome | Decreased albumin Increased alpha2 Normal/increased beta |
| Advanced cirrhosis | Decreased albumin Increased gamma Beta and gamma peaks |
| Polyclonal gamma globulin elevation Including cirrhosis, chronic infection, sarcoidosis, tuberculosis, endocarditis, rheumatoid-collagen diseases |
Increased gamma globulins with broad peaks |
| Hypogammaglobulinemia Including light-chain multiple myeloma |
Decreased gamma globulins Other globulins normal |
| Monoclonal gammopathy Including myeloma, Waldenstrom macroglobulinemia, gammopathies |
Thin spikes in beta and gamma globulins |
| Anemia: Iron deficiency | Increased beta1 due to increased free transferrin. |
| Antibody deficiency Including congenital antibody deficiency with recurrent childhood infections, as well as acquired antibody deficiencies induced by medications, malignant tumors, or nephrotic syndrome |
Albumin normal Alpha1, alpha2, and beta normal Gamma decreased |
| Inflammation: Acute in the early stages Including early infection, burns, necrosis, trauma, and chemical injury |
Albumin normal or decreased Alpha1 and alpha2 increased Beta and gamma normal |
| Inflammation: Acute in the latter stages Including pneumonia, bacterial meningitis, pyelonephritis, sepsis |
Albumin decreased Alpha1, alpha2, and gamma increased Beta normal |
| Inflammation: Chronic Including inflammatory disorders such as chronic infections (e.g., viral hepatitis, tuberculosis, bronchiectasis, lues, osteomyelitis), IBD, rheumatoid arthritis, and connective tissue diseases. |
Albumin decreased Alpha1, alpha2, and beta normal Gamma increased |
| Inflammation: Chronic, active Including exacerbated rheumatoid arthritis, lupus, hepatitis, endocarditis |
Albumin decreased Alpha1 and alpha2 increased Beta normal Gamma increased |
| Liver failure Including cirrhosis, hepatitis, necrotizing hepatitis, toxic/alcohol liver damage |
Albumin decreased Alpha1 and alpha2 normal or decreased Beta normal Gamma significantly elevated |
| Malignant tumors | Albumin decreased Alpha1 and alpha2 increased Beta normal Gamma normal, increased, or decreased |
| Nephrotic syndrome Including kidney disease with glomerular damage and urinary protein loss of greater than 3 grams per day |
Albumin decreased Alpha1 decreased Alpha2 significantly increased Beta increased Gamma decreased |
| Pregnancy | Albumin decreased Alpha1 and gamma normal 1st T: Alpha2 globulins increase 2nd, 3rd T: Beta globulins may increase due to increased transferrin with iron deficiency anemia |
Protein Biomarkers: Total Globulin
Protein Biomarkers: Albumin Globulin Ratio
Pagana, Kathleen Deska, et al. Mosby's Diagnostic and Laboratory Test Reference. 16th ed., Mosby, 2022.
Vavricka, Stephan R et al. “Serum protein electrophoresis: an underused but very useful test.” Digestion vol. 79,4 (2009): 203-10. doi:10.1159/000212077