Research Blog

April 3, 2024

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):

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, 3^rd 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 1^st T: Alpha2 globulins increase 2^nd, 3^rd 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.