The remaining plasma proteins comprise hundreds of distinct protein molecules. Plasma proteins are heterogenous in nature and involved in many complex functions within the body.
Abnormalities in plasma proteins may be primary the cause of specific pathologies or secondary the result of a wide range of disease processes. Abnormal proteinuria can also result from various medical conditions. The reasons why a GP may request measurement of plasma protein include investigations of symptoms, allergies, and immunity see Box 1. Liver panel tests , for example, those requested as part of drug monitoring, may reveal protein abnormalities that require further investigation.
Testing urine for protein may assist in the diagnosis of urinary infection, primary renal disease including nephrotic syndrome, secondary renal disease for example in diabetes, multiple myeloma, and pre-eclampsia in pregnancy.
The conditions associated with abnormal globulin and albumin levels are detailed below and summarised in Table 1. Decreased globulin levels as a fraction of total protein are seen in individuals with malnutrition and patients with nephrotic syndrome when there is renal protein loss. High total protein levels associated with increased globulin may be seen in dehydration, in response to acute infections such as pneumonia and hepatitis, and in chronic inflammatory conditions such as rheumatoid arthritis and systemic lupus erythematosus SLE.
Other causes of a low serum albumin level include severe malnutrition which may accompany alcohol-related liver disease.
Severe inflammatory conditions or shock may also be associated with low serum albumin levels, when a catabolic state develops and the synthetic function of the liver switches to the production of other proteins. An important symptom of low serum albumin is the development of peripheral oedema. High serum albumin levels generally reflect dehydration. Causes of transient elevated proteinuria include: 1 3. Urine may test falsely positive for protein when the sample has been contaminated by vaginal mucous.
Causes of persistent proteinuria include: 1 3. If serum albumin is low and nephrotic syndrome is suspected, testing the urine for protein will help inform the diagnosis. C-reactive protein is an acute-phase reactant; a protein synthesised by the liver and released into the blood in response to tissue injury, infection, or other inflammatory processes. Its physiological role is thought to involve binding to the surface of dead or dying cells and some types of bacteria to activate the complement system.
In chronic inflammatory conditions, CRP level can be valuable in monitoring disease activity, with high levels suggestive of an acute exacerbation or ineffective treatment and falling or low levels indicative of remission. Raised CRP is a feature of infection or inflammation, but it is a non-specific marker of an acute response. C-reactive protein typically returns to normal when the acute infective or inflammatory process is resolved.
Although standard liver panel tests and on-site urine protein testing give a general indication of protein levels, protein electrophoresis can be used to separate the mixture of proteins present in either plasma or urine into subdivisions to provide additional diagnostic information.
The distance travelled by each protein depends on a range of variables, including its molecular size and electrical charge. The separated proteins are then visualised using a stain, which reveals a characteristic pattern of bands. Serum proteins are separated into six major groups by protein electrophoresis: albumin and alpha 1 , alpha 2 , beta 1 , beta 2 , and gamma globulins. The size of each band gives a qualitative indication of the amount of that protein fraction.
This pattern of bands is often converted into a graph, with vertical spikes or peaks where there are large amounts of protein and smaller peaks or valleys where there are small amounts of protein. Abnormal electrophoresis patterns are associated with a variety of different pathological conditions. Your doctor will interpret your results in conjunction with your medical history and other test results. The conditions we discuss here are commonly associated with high globulin, but this single symptom is not enough for a diagnosis.
Work with your doctor to discover what underlying condition might be causing high globulin levels and to develop an appropriate plan to improve your health.
Studies are now revealing that high globulin gamma gap is linked with an increased risk of disease and death. A review of more than 12k people found an increased risk of death from all causes in people with a gamma gap above 3.
Similarly, a gamma gap over 3. In an observational study of 27, healthy people, a low albumin-to-globulin ratio similar to a high gamma gap , was linked with increased rates of cancer and death [ 13 ]. One possible answer is that increased production of immunoglobulins is linked with inflammation ; inflammatory factors like c-reactive protein and IL-6, for example, increase immunoglobulins [ 12 ]. Inflammation also rises with aging, which could explain why older people with higher gamma gaps were more likely to die than those with lower gamma gaps.
The most important thing is to work with your doctor to treat any underlying conditions causing your high globulin levels. The additional strategies below are other things that you may try if you and your doctor determine that they could be appropriate. Exercise more often. Both aerobic and strength exercise may help significantly decrease globulin levels in people [ 14 ].
In both men and women, more days per week of either aerobic or strength exercise were significantly associated with lower globulin [ 14 ]. You may also need to stop taking protein supplements, as these may be causing higher protein and globulin levels [ 15 ]. Drink more water to prevent dehydration [ 2 , 16 ]. Zinc may help prevent dehydration due to diarrhea, according to limited studies [ 17 ].
Electrolytes can also help with dehydration due to diarrhea [ 18 ]. Limit alcohol intake; alcohol can worsen dehydration [ 19 ].
Try to reduce stress, since acute stress may increase certain types of globulins [ 20 ]. The conditions we discuss here are commonly associated with low globulin, but this single symptom is not enough for a diagnosis. Work with your doctor to discover what underlying condition might be causing low globulin levels and to develop an appropriate plan to improve your health. Where the gamma fraction is increased, it can then be further established whether this is a narrow spike-like increase of a single immunoglobulin a monoclonal rise or a broader-based increase polyclonal rise.
Monoclonal rises are then further evaluated with immunoelectrophoresis or immunofixation electrophoresis see below. Monoclonal spikes are more likely to have a malignant cause, with multiple myeloma being the most common of these.
However, the most common cause of a monoclonal rise is monoclonal gammopathy of uncertain significance MGUS which is usually a benign condition. Abnormal immunoglobulins produced in excess monoclonally are also known as paraproteins.
Immunoelectrophoresis or immunofixation electrophoresis is usually performed when SPEP has found the presence of increased gammaglobulin levels in order to further establish the nature of the abnormality. It identifies the type of gammaglobulin. This is commonly used in the diagnosis of myeloma. Causes of raised immunoglobulin levels Electrophoresis will establish if these are polyclonal or monoclonal rises.
The most common rise in immunoglobulin levels is polyclonal, and due to immune system activity caused by infection or autoimmune diseases.
Blood tests can be done which measure the amount of IgE antibodies which have been produced in response to specific allergens.
Blood allergy tests are more expensive and less sensitive than skin prick testing, but can be useful in certain situations - for example, when there is a risk of anaphylaxis, or severe skin rashes, or when the patient needs to continue taking antihistamines.
Hundreds of different allergens can be tested for in this way. A raised globulin level may be a relatively common coincidental finding. The work-up to establish the cause involves history, examination and further investigations to determine which of the conditions listed above may be causing the abnormality. This work-up would include:.
See also the Therapeutic Immunoglobulins article. Bird JM ; Investigating an incidental finding of a paraprotein. Aust Fam Physician. Serum globulin electrophoresis ; MedlinePlus.
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