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Serum Protein Electrophoresis

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:

Protein Electrophoresis Components (Pagana 2022, Vavricka 2009)

Albumin, prealbumin

Alpha1 Globulins:

  • Lipoprotein (HDL)
  • Glycoprotein
  • Antitrypsin

Alpha2 Globulins:

  • Macroglobulin
  • Haptoglobins
  • Ceruloplasmin
  • Prothrombin
  • Cholinesterase

Beta1 Globulins:

  • Other lipoproteins
  • Transferrin
  • Plasminogen
  • Complement proteins

Beta2 Globulins:

  • Fibrinogen

Gamma Globulins (primarily IgG):

  • IgA
  • IgD
  • IgM
  • IgG
  • IgM

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.

SPE Patterns by Component (Vavricka 2009)

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

SPE Patterns by Disorder (Pagana 2022, Vavricka 2009)

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

Optimal Takeaways

  • Assessing serum proteins and protein electrophoresis requires a deeper dive into the breakdown of serum protein fractions and a detailed clinical history.
  • Without a specific elevation in any one globulin fraction, the results might not point towards a single, clear-cut diagnosis but instead suggest a need for a broader assessment of the patient's health, including consideration of chronic conditions, nutritional status, and possible autoimmune processes.

Read more about ODX serum protein levels here:

Protein Biomarkers: Albumin

Protein Biomarkers: Total Globulin

Protein Biomarkers: Albumin Globulin Ratio

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References

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

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