Protein electrophoresis test explained

The protein fractions test (protein electrophoresis) is a way of separating the proteins present in blood serum by their electrical charge - they form two main groups: albumin and globulins. Albumin is the most abundant protein in the blood; it maintains the fluid balance in the blood vessels and transports various substances. During electrophoresis the globulins separate into four fractions - alpha-1, alpha-2, beta and gamma globulins - each of which contains different proteins: from the acute-phase proteins produced during inflammation to the antibodies (immunoglobulins) that make up most of the gamma fraction. Because different diseases affect different fractions in their own characteristic way, the shape of the electrophoresis curve helps to tell apart liver disease, chronic inflammation, protein loss through the kidneys and plasma cell disorders (for example myeloma, where a single sharp peak appears in the gamma zone). The test is most often ordered together with total protein and albumin, when their values are unclear.

• When total protein or albumin in the blood is outside the reference range and the reason is unclear
• When liver disease (for example cirrhosis) or kidney disease is suspected, with protein lost in the urine
• When there is swelling of the legs, ankles or abdomen, tiredness, unexplained weight loss, loss of appetite, nausea or vomiting, jaundice, or blood in the urine
• When a chronic inflammatory or autoimmune disease is suspected (rheumatoid arthritis, systemic lupus erythematosus)
• When a plasma cell disorder such as myeloma is suspected, with an unusual peak seen in the gamma globulin zone
• In a chronic infection such as viral hepatitis or HIV

A raised total protein, or raised individual globulin fractions, is most often linked to a chronic infection (viral hepatitis, HIV), an inflammatory or autoimmune disease, or a plasma cell disorder such as myeloma. In that last case a sharp, narrow peak is seen in the gamma zone of the electrophoresis curve. The cause is easier to tell apart when liver markers and immunoglobulins are assessed alongside.

• Chronic infection - viral hepatitis, HIV
• A plasma cell disorder (myeloma) - a single sharp peak in the gamma globulin zone
• Chronic inflammatory or autoimmune disease - rheumatoid arthritis, systemic lupus erythematosus
• Genetically determined changes or leukaemia - can raise the albumin to globulin (A/G) ratio

What a doctor usually looks at next:

• Liver markers and immunoglobulins (IgG, IgA, IgM) - these help pin down more precisely which fraction has changed and why
• An immunofixation test, if a monoclonal gammopathy or myeloma is suspected
• Inflammatory markers (CRP, ESR), if an autoimmune disease is suspected
• When to repeat the test, to assess the change over time

A low result

A low total protein or albumin most often points to liver disease, kidney disease with protein lost in the urine, poor nutrition, or gastrointestinal diseases that interfere with protein absorption. It can show up as swelling of the legs, ankles or abdomen, tiredness, unexplained weight loss, loss of appetite, nausea, jaundice or blood in the urine.

• Liver disease, including cirrhosis
• Kidney disease, where protein is lost in the urine
• Poor nutrition (not enough protein)
• Malabsorption syndromes - coeliac disease, Crohn's disease
• Autoimmune disease (for example systemic lupus erythematosus) - can lower the A/G ratio

• Swelling of the legs, ankles, lower legs and/or abdomen
• Tiredness
• Unexplained weight loss
• Loss of appetite, nausea or vomiting
• Jaundice
• Blood in the urine

What a doctor usually looks at next:

• Liver function markers (ALT, AST, bilirubin) - if liver disease is suspected
• Kidney markers and protein in the urine - if protein loss in the urine is suspected
• A nutritional assessment and gastrointestinal investigations, if malabsorption is suspected
• When to repeat the test, to assess the change over time

How it differs from total protein and albumin tests

Total protein and albumin show only the overall amount, while protein fractions (electrophoresis) reveal how that protein is distributed between albumin and the separate globulin groups. This makes it possible to tell apart more precisely whether the change is driven by inflammation, liver disease, kidney disease or a plasma cell disorder.