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Your blood carries dozens of proteins, each with a different job. Some shuttle nutrients, some fight infections, some help blood clot. When something goes wrong in your body, the mix of proteins shifts in characteristic ways. Total protein, measured as part of a protein electrophoresis panel, tells you whether the overall amount of protein in your blood is normal, while the electrophoresis pattern shows which specific protein groups are driving any imbalance.
This distinction matters because a normal total protein number can hide a serious problem. A blood cancer might be pumping out a single abnormal protein that raises one fraction while another fraction drops, leaving the total looking fine. Or a weakened immune system might produce too few antibodies, but the total stays in range because other proteins compensate. The electrophoresis pattern catches what the single number misses.
Total protein in your blood is not a single molecule. It is the sum of two main groups: albumin and globulins. Albumin, made by your liver, accounts for roughly 55 to 65% of the total. It carries hormones, nutrients, and medications through your bloodstream and keeps fluid from leaking out of your blood vessels.
Globulins are everything else. They include antibodies (also called immunoglobulins) made by your immune system, proteins that help blood clot, and proteins that carry fats and metals. When the lab runs protein electrophoresis, it separates your blood sample into distinct zones: albumin, alpha-1, alpha-2, beta, and gamma. The gamma zone is where most antibodies land.
A simple calculation, total protein minus albumin, gives you what is called calculated globulin. This one number can serve as a quick screen for immune problems. If it is too low, your body may not be making enough antibodies. If it is too high, inflammation, infection, or even a blood cancer may be driving up one or more globulin types.
One of the most valuable uses of this test is flagging monoclonal gammopathies, a family of conditions where a single clone of immune cells produces an abnormal protein. The most serious of these is multiple myeloma, a cancer of the plasma cells in your bone marrow. When total protein rises above 80 g/L (8.0 g/dL), it can trigger a reflex electrophoresis test that reveals a sharp spike in one zone, the hallmark of a monoclonal protein.
In a study of over 13,000 patients in general practice, serum protein electrophoresis alone detected about 90% of clinically significant monoclonal protein diseases, with a specificity of roughly 96%. Adding a serum free light chain test pushed sensitivity above 95%. A Chinese hospital program that embedded routine monoclonal protein screening into standard lab panels found that myeloma was diagnosed earlier and patients had better outcomes compared to those diagnosed only after developing symptoms.
Subtle distortions on the electrophoresis pattern, rather than full spikes, are more commonly linked to a precursor condition called MGUS (monoclonal gammopathy of undetermined significance). MGUS itself is not cancer, but it carries a small ongoing risk of progressing to myeloma or a related malignancy, which is why serial monitoring matters.
The flip side of too much protein in the gamma zone is too little. A low gamma fraction or low calculated globulin can signal that your immune system is not making enough antibodies, a condition called hypogammaglobulinemia. People with this condition are vulnerable to recurrent infections, particularly of the lungs and sinuses, and often go years before being diagnosed.
In adults, a gamma fraction cutoff of 7.15 g/L caught 100% of people with clinically low IgG (immunoglobulin G, the most abundant antibody class) while correctly clearing about 97% of people with normal levels. In children and adolescents, the gamma fraction also reached 100% sensitivity across age groups.
Calculated globulin, the simpler version that does not require full electrophoresis, performed nearly as well. In adults, a calculated globulin below 24 g/L identified 86% of those with antibody deficiency, with 92% specificity. These numbers make protein electrophoresis one of the most accessible, low-cost screens available for a condition that is often missed for years.
The ratio of albumin to globulin (often called the A/G ratio or AGR) has emerged as a surprisingly strong predictor of death from many causes. The pattern is consistent: low albumin relative to globulin signals worse outcomes.
| Who Was Studied | What Was Compared | What They Found |
|---|---|---|
| About 18,000 Italian adults aged 65 and older, followed for 13 years | Albumin at or below 35 g/L versus above 40 g/L | About 60% higher risk of death from all causes, including cancer and vascular disease |
| Over 104,000 U.S. adults starting hemodialysis | Total protein below 5.5 g/dL versus 6.5 to 7.0 g/dL | About 34% higher risk of death; low A/G ratio (below 0.75) carried 45% higher risk |
| Cancer patients across 10 U.S. national survey cycles | Albumin at or below 4.2 versus above 4.2 g/dL | About twice the risk of dying from cancer |
What this means for you: if your total protein is normal but the balance between albumin and globulin is off, the A/G ratio can reveal risk that neither number shows on its own. A high globulin fraction often reflects chronic inflammation, infection, or immune activation, all of which accelerate aging and disease.
A low albumin-to-globulin ratio also predicts new kidney disease. In a Korean community study of over 8,000 adults without kidney disease, those in the lowest fifth of A/G ratio (below 1.26) were about 65% more likely to develop chronic kidney disease over roughly nine years of follow-up compared to those with the highest ratios. Each 0.2-point drop in the ratio raised the risk by about 17%.
This association held even after accounting for standard inflammatory markers like CRP (C-reactive protein, a common blood marker of inflammation) and white blood cell count, suggesting that the A/G ratio captures something about systemic stress or immune activation that those simpler tests miss. If your A/G ratio is trending downward over time, it may be worth checking kidney function with eGFR (estimated glomerular filtration rate, a measure of how well your kidneys filter waste) and a urine albumin test.
Beyond myeloma, the protein profile on electrophoresis has broader cancer-detection value. Cancer patients as a group tend to show lower total protein and albumin, with increases in the alpha-1, alpha-2, and gamma globulin fractions and a decreased A/G ratio. In one study, this pattern distinguished cancer patients from healthy individuals with moderate accuracy.
A newer composite index called the inflammatory protein ratio (IPR), built from electrophoresis fractions, detected active cancer with 88% sensitivity and 75% specificity, outperforming CRP and several blood-count-based inflammation scores. While no single protein marker is a cancer test on its own, a persistently abnormal electrophoresis pattern, especially with rising alpha globulins, warrants further investigation.
These ranges come from a large study of over 78,000 healthy adults and children in Namibia, measured by standard laboratory methods. They are broader than many routine lab intervals and should be treated as general orientation, not rigid targets. Your own lab may report slightly different cutpoints.
| Category | Range (g/L) | What It Suggests |
|---|---|---|
| Low | Below 51 | Possible liver disease, malnutrition, protein loss through kidneys or gut, or overhydration |
| Normal | 51 to 91 | Typical range across all ages and sexes |
| High | Above 91 | Possible dehydration, chronic inflammation, infection, or monoclonal protein production |
Age matters. Children under five have lower normal values (around 48 to 86 g/L), while adults aged 36 to 65 have the highest (54 to 93 g/L). After age 65, the upper end dips slightly to about 89 g/L. Many labs use narrower reference intervals (for example, 60 to 80 g/L), which can cause mild elevations to be overlooked or normal low values to be flagged as abnormal.
Compare your results within the same lab over time for the most meaningful trend. Assay methods differ enough between labs that switching facilities can create false shifts in your numbers.
Total protein has a low within-person biological variation of about 3 to 4% over months in healthy people. That means a shift of more than about 8% between two readings at the same lab is likely real rather than random noise. But several factors can produce misleading results on any single draw.
A single total protein result is a snapshot. Serial readings over time are far more informative, particularly for two scenarios. First, if you have a borderline high protein or a subtle electrophoresis distortion, tracking whether it stays stable, grows, or resolves tells you whether this is MGUS (stable) or something progressing toward myeloma. Second, if your calculated globulin or gamma fraction is in the low-normal range, trending it over a year or two can reveal a gradual decline toward antibody deficiency before you start getting recurrent infections.
For the electrophoresis M-spike (the sharp peak seen in monoclonal protein diseases), the combined biological and analytical variation is about 8%, meaning changes smaller than roughly 15 to 20% may fall within expected noise. Urine M-spikes and serum free light chains are even more variable, with total coefficients of variation around 28 to 36%. Keep this in mind before reacting to small shifts.
A reasonable schedule: get a baseline reading, repeat in 6 to 12 months if anything looks borderline, and then annually if you are monitoring a stable pattern. If you are actively treating a condition that affects protein levels, your physician may want readings every 3 to 6 months.
If your total protein is high, the next step depends on how high and what the electrophoresis pattern shows. A clearly elevated total protein with a visible M-spike should prompt immunofixation (a test that identifies the exact type of abnormal protein) and serum free light chain measurement. These two companion tests together catch over 95% of clinically significant monoclonal protein diseases. A hematologist is the right specialist for this workup.
If your total protein is low and calculated globulin is below 24 g/L, ask for a direct measurement of IgG, IgA, and IgM (the three main antibody classes). If IgG is confirmed low, an immunologist can evaluate whether you have a primary antibody deficiency or whether something else, like medication or protein loss, is responsible.
If the A/G ratio is low but neither albumin nor globulin is dramatically abnormal, consider adding kidney function tests (eGFR, urine albumin-to-creatinine ratio) and inflammatory markers (CRP, ESR, which is the erythrocyte sedimentation rate, a measure of inflammation). A persistently low A/G ratio with no obvious explanation deserves a closer look at liver function, chronic infection, and autoimmune conditions. In all cases, retest before acting on a single abnormal value.
Total Protein (Protein Electrophoresis) is best interpreted alongside these tests.