Protein electrophoresis: what it is, what it tells you and when it’s tested

Protein electrophoresis splits the proteins in your blood into groups, called fractions: albumin, alpha-1, alpha-2, beta and gamma globulins. Each fraction is a family of proteins. The trace shows whether a family has gone up or down, or whether one single protein is in excess.

When it’s tested

Doctors order it when total protein is high or low, when the ESR is high for no clear reason, or with anaemia, high calcium, kidney problems, bone pain or frequent infections. It is also used to follow people who already have a monoclonal protein.

It is not a screening test for people who feel well. It is done when there is a clear question, and it often leads to other tests.

That is why Rosa does not run it. Instead it measures albumin, CRP, haemoglobin, white blood cells, calcium and creatinine, which flag many of the problems doctors order it for.

What it tells you, and what it does not

It shows which family of proteins has changed. For example, the alphas rise with recent inflammation, the gammas with inflammation that lasts.

It also shows a narrow spike, the monoclonal protein: many copies of one single protein, made by a single group of cells.

On its own it does not give a diagnosis. A spike needs typing with other tests, and a broad rise needs explaining with your history and an examination.

That is why it is read together with other tests:

• Total protein: It turns the percentages into g/dL
• Albumin: It is the largest fraction
• CRP: It confirms whether there is inflammation
• Immunoglobulins: They show which antibodies are up

Normal protein electrophoresis values

Each fraction has its own range, printed next to it on your report. The limits change with the method, capillary or gel, and with the lab. So there is no table that fits everyone: the one on your report is what counts.

Albumin is always the largest fraction, more than half of the total. The gamma globulins usually come next.

Your report gives each fraction as a percentage and often also in g/dL or g/L, worked out from total protein. If it says monoclonal component, or spike, the lab has seen one single protein in excess.

If your gamma globulins are high or low

• High gamma globulins: Usually inflammation, an infection or the liver. Less often a spike, almost always one to follow over time.
• Low gamma globulins: They can come from some medicines, protein lost through the urine or gut, or a weak immune system. Talk to your doctor.

How to read protein electrophoresis

The fractions, from top to bottom on the report, and what most often moves them.

• Albumin: It falls with liver disease, protein loss through the kidneys or gut, malnutrition and inflammation.
• Alpha-1 globulins: They rise with recent inflammation. If they are very low, your doctor may look for a rare alpha-1 antitrypsin deficiency.
• Alpha-2 globulins: They rise with inflammation and when the kidneys leak a lot of protein.
• Beta globulins: They rise with iron deficiency, through transferrin, and with high cholesterol. Sometimes a spike shows up here.
• Gamma globulins: Mostly antibodies. They rise with inflammation and infections that last and with liver disease. A narrow spike is a monoclonal protein.

What can skew the result

A few things change the trace without any disease. It helps to know them before your blood test.

• An infection right now: A cold or flu raises the alphas for a while. It is better to test once you are well.
• Plasma instead of serum: With the wrong tube, fibrinogen can look like a small spike. The lab knows how to spot it.
• Drinking too little: With little water, all proteins look higher in g/dL.
• Very high cholesterol: It can raise the beta globulins without any other problem.

When to worry

Talk to your doctor if:

• Your report flags a monoclonal component, or a spike.
• Your gamma globulins are high or low compared with your report.
• You also have anaemia, high calcium, high creatinine or new bone pain.
• You have frequent infections, tiredness that does not go away or weight loss for no reason.
• You have severe back pain with weakness or numbness in your legs, or feel confused and very thirsty: call 112 or go to the emergency department.

Frequently asked questions

What are normal protein electrophoresis values? Each fraction has its own range, which changes with the method and the lab. Albumin is always more than half. The range printed on your report is what counts.

Protein electrophoresis: when should I worry? When there is a spike, a monoclonal protein, or when a fraction is far out of range together with anaemia, high calcium or kidney problems. Even then it is often nothing serious, but your doctor should see it.

What does a monoclonal protein mean? That there is a lot of one single protein in your blood, made by a single group of cells. Most often it is a benign form that is checked over time. Your doctor types it with other tests and, if needed, refers you to a haematologist.

High alpha-2 globulins: what does it mean? Usually inflammation going on. They also rise when the kidneys leak a lot of protein. Your doctor reads them with CRP, albumin and a urine test.

Do I need to fast for protein electrophoresis? Fasting is usually asked, as for other blood tests. Follow your lab’s instructions.

Does Rosa run protein electrophoresis? No. Rosa measures albumin, CRP, haemoglobin, white blood cells, calcium and creatinine. If your doctor wants electrophoresis, they order it separately.

Sources

• O’Connell and colleagues, understanding and interpreting serum protein electrophoresis. American Family Physician, 2005. PMID 15663032
• MedlinePlus, U.S. National Library of Medicine: Protein electrophoresis, serum. MedlinePlus, Protein electrophoresis, serum
• Kyle and colleagues, long-term follow-up of monoclonal gammopathy of undetermined significance. New England Journal of Medicine, 2018. PMID 29342381
• Rajkumar and colleagues, International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncology, 2014. PMID 25439696