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Elevated Serum Protein

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Last Updated: 02 July 2021

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General | Latest Info

A healthy 54 year - old man without a past medical history presents for routine physical exam for his insurance company. His blood work reveals total protein of 9. 4 G / dl and Albumin of 3. 0 G / dl. What should be included in these patients ' diagnostic workup? Elevate TP: Albumin ratio often necessitates finding protein responsible for such elevation. Plasma proteins largely consist of albumin and globulins such as immunoglobulins, carrier proteins, and acute phase reactants. Elevate globulin levels are concerning. An important question to ask oneself in workup of elevated proteins is whether there is an increase in multiple immunoglobulins or in one specific clone. Monoclonal proteins are made by proliferation of single clone of plasma cells. In order to assess for presence of Monoclonal Protein, SPEP should be order. In this test, patients ' serum is placed into agarose medium that separates proteins based on size and charge. A Typical Gamma M Spike means that we have large amount of very specific protein. For further characterization of M - Spike, immunofixation study should be order. If uses Monoclonal antibody probes to determine the isotype of Monoclonal Protein. If is often used when presence of M - Protein cannot be ascertained using SPEP, but clinical suspicion is high. The newer test known as Serum free light chains is even more sensitive, and has rendered true non - secretory myeloma into a rare entity. Look for Monoclonal Protein in urine, UPEP and urine IF can also be useful. Lastly, hematologist may be needed for bone marrow biopsy as well. Note discreet bands in IgG lane and Kappa lane - clearly identifying Kappa restrict IgG Protein. Once above diagnostic studies are obtain, physicians can often use clinical signs and symptoms along with biopsy results and M Spike characteristics to help define the clinical disease state. For example: one should be mindful of patients who present with elevated proteins plus nephrotic syndrome, carpal tunnel syndrome, autonomic neuropathy and / or cardiomyopathy. Amyloidosis should be high in differential as plasma cells produce amyloid proteins that deposit in variable organs. Fat pad biopsy can help to cinch diagnosis. Patients with significant Protein abnormalities should be referred to a hematologist for evaluation and treatment as a variety of options exist and many Protein disorders carry serious risks and progression to more serious entities. Treatment options for MM, while largely incurable, include conventional agents like melphalan, steroids, or auto - transplant as well as newer agents like thalidomide, lenalidomide or Bortezomib. The risk of progression to MM from MGUS is 1 - 2% per year and patients need to be assessed yearly for signs of CRAB. For SMM, risk is higher, and follow - up is warranted every 3 to 4 months. Abnormal Serum free light chain ratio is also predictive of progression to frank multiple myeloma. This progression is independent of size and type of Serum Monoclonal Protein.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions

Howas the Test Done?

A technician will take a sample of your blood. Sometimes this is taken from a vein in your arm. It can also be done with finger prick. For newborns, itas done with aheel sticka - blood is drawn through a small puncture of the heel. Some drugs, like birth control pills, reduce the amount of protein in your blood. This can skew your test results. Make sure your doctor knows all the medicines you are taking, as well as any herbs, vitamins, or illegal drugs. Make sure to drink plenty of water before taking this test. Being dehydrated can change results. Lab results should be back in about 12 hours.


Results

Serum total proteins of male group, female group, and overall group negatively correlate with age. Regression coefficients were significant in all of the groups. The linear regression equation of total protein with age in the male group was y = - 0. 1342 x + 77. 363. Thus, serum total protein value of males aged 60 was reduced by 0. 1342 g / L in each additional year. The linear regression equation of total protein with age in the female group was y = - 0. 304 x + 90. 673. Thus, total protein value of women aged 60 was reduced by 0. 304 g / L with each additional year of age. The linear regression equation of total protein with age in the overall group was y = - 0. 2136 x + 83. 577. Thus, total protein value of elderly aged 60 was reduced by 0. 2136 g / L with each additional year. Serum total protein levels also decrease faster in females than in males with increasing age.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions

Results

3 grams per deciliter or 64 to 83 grams per liter albumin: 3. 5 to 5. 0 G / dL or 35 to 50 G / L Alpha - 1 globulin: 0. 1 to 0. 3 G / dL or 1 to 3 G / L Alpha - 2 globulin: 0. 6 to 1. 0 G / dL or 6 to 10 G / L Beta globulin: 0. 7 to 1. 2 G / dL or 7 to 12 G / L Gamma globulin: 0. 7 to 1. 6 G / dL or 7 to 16 G / L examples above are common measurements for results of these tests. The normal value range may vary slightly among different laboratories. Some labs use different measurements or test different samples. Talk to your provider about the meaning of your specific results.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions

What causes high blood protein?

Your liver is in charge of making most of the proteins that are in your blood. They are important for good health. Albumin. This carries medicines and hormones throughout your body. It also helps with tissue growth and healing. Globulin. This is a group of proteins. Some of them are made by your liver. Others are made by your immune system. They help fight infection and transport nutrients. The Total serum protein test measures all proteins in your blood. It can also check the amount of albumin you have compared to globulin, or whatas call your G ratio. Healthy people have little more albumin than globulin, but if are sick, this wonat be the case.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions

Definition

Hundreds of proteins dissolve in plasma. By measuring concentration of these proteins, clinicians can obtain information regarding disease states in different organ systems. Measurement of protein is done on serum, which is fluid that remains after plasma has clot, thus removing fibrinogen and most of the clotting factors. Total protein content provides some information regarding patient's general status; more clinically useful data is obtained from fractionating total protein. The normal serum protein level is 6 to 8 g / dl. Albumin make up 3. 5 to 5. 0 g / dl, and the remainder is total globulins. These values may vary according to individual laboratory.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions

Technique

When require, specific proteins can be identified using one of family of tests termed immunofixation electrophoresis. 9 in these tests, proteins are first separated by electrophoresis and then react with specific antibody. If an antibody reacts with protein being investigate, antibody - protein complex remains in gel while other proteins are washed away, allowing protein to be identified and quantify. This technique is useful in assessment of multiple myeloma. Immunoglobulin E antibodies to specific antigens can be measured using radioallergosorbent testing or enzyme - link immunosorbent assay techniques. These techniques are valuable in assessment of allergies, for example, when there is a risk of anaphylaxis. 9 range of other techniques, including enzyme immunoassays, can be used to quantify serum levels of specific antibodies, such as rubella and hepatitis B antibodies. These techniques are used both to diagnose current infection and to confirm presence of immunity. Preparation of specific antigen is incubated with specimen of patients ' serum. If an antibody under investigation is present, it will become coupled to antigen. Analytic processes are then used to quantify the amount of antibodys present in the serum.


Understanding serum protein electrophoresis

Although standard liver panel tests and on - site urine protein testing give general indication of protein levels, protein electrophoresis can be used to separate a mixture of proteins present in either plasma or urine into subdivisions to provide additional diagnostic information. 9 In this process, electric current is used to move protein mixture across a thin layer of gel. Distance travel by each protein depends on a range of variables, including its molecular size and electrical charge. Separated proteins are then visualise using stain, which reveals the 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 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.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions

Basic Science

Affinity binding is descriptive characteristic estimate for bundle of amino acids, on site of plasma protein, that interact and accommodate ligands to bind into binding cavities. In plasma proteins, some residues have a more important role than others for binding ligands in high - affinity binding cavities, and this discrepancy in importance depends, inter alia, on functional groups of each ligand. Also, some changes in residues may occur and significantly modulate the inner composition of high - affinity binding pockets and their peptide outer surroundings. For example, polar AAs may be replaced with neutral or hydrophobic ones, or positive residues may be replaced with negative ones and vice versa. Consequently, alteration of nucleotides and peptides influences the extent of binding to plasma proteins. To better understand this influence, composition in AAs of high - affinity binding sites of most frequent variants for human ALB and AGP is discussed next. Free Cys34, known for its antioxidant role, is well conserved in humans. About 70 - 80% of Cys34 in plasma contains free sulfhydryl group, while the other 25% forms disulfide bond with small sulfhydryl compounds, such as cysteine, homocysteine, or glutathione. Another well - conserved residue in ALB is Trp214. It is situated in a major interdomain cluster of hydrophobic residues, and precisely in the conserved sequence of loop 4. This hydrophobic residue is important, just like disulfide bridges, for holding together two halves of heart - shape ALB. Absorption of UV light by ALB is particularly attributed to Trp214, which is quite appreciated as fluorescent residue in binding studies for measurement of thermodynamic parameters. In subdomain IIA of mature ALB, Site I has voluminous cavity and it is constituted from 177 AA to 291 AA. In subdomain IIIA, Site II has smaller cavity and it is constituted from 367 AA to 491 AA. Residues most involved in binding ligands to two high - affinity binding cavities of human ALB, other than Trp214 and Cys34, are present in Table 2. Each binding site includes a hydrophobic cavity with distinct polar or ionic residues within it or its surroundings. Therefore, hydrophobic, polar, and electrostatic interactions play a key role in determining affinity of ligands for both sites I and II. Interior Site I's pocket cavity is predominantly hydrophobic delimit by residues Trp214, Leu219, Phe223, Leu238, His242, Leu260, Ile264, Ser287, Ile290, and Ala291; so mainly hydrophobic interactions are dominant. The site also contains two clusters of polar or ionic residues, inner one towards bottom of the pocket composed of Tyr150, His242, and Arg257; and the outer strictly - cationic cluster at the cavity entrance composed of Lys195, Lys199, Arg218, Arg222. Such placement of residues orchestrates binding of aromatic compounds with centrally located negative or electronegative features. Thus, bulky heterocyclic anions preferentially bind to Site I between apolar Leu238 and Ala291 in the centre of the pocket.


Measurement of Proteins

There are several ways to measure proteins. Chemical methods rely on properties of amino acids or peptide bonds that are common to all proteins. Activity assay measures the biological function of proteins. Immunoassays use antibodies to recognize unique structural domains on Proteins. All of these methods are applied in clinical laboratories to measure proteins and to detect abnormalities that cause or result from disease. Measurement of total protein concentration in serum has limited clinical value; measurement of specific proteins by their activity or via immunoassay provides more specific diagnostic information. Serum protein electrophoresis separates serum proteins into general classifications based on size and charge; immunoelectrophoresis and immunofixation electrophores are modifications of SPE that provide greater specificity based on immunoreactivity of proteins, primarily immunoglobulins. Proteomics is a relatively new approach to diagnostic use of proteins; it involves high - resolution chromatographic methods to separate and to map many proteins, with the goal of detecting global variations in protein expression that are associated with disease.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions

Clinical Significance

Denis 1 in 1856, was probably the first to report an investigation of the action of various salts on separation of serum albumin from serum globulin. Hammerstein 2 in 1878 reported utilization of the precipitating effect of salt for quantitative estimation of albumin and globulin in horse and human serum. In 1882, Burckhardt 3 found that in starving dogs albumin concentration of serum fell while globulin concentration remained stationary. In 1912, Epstein 4 reported that in 12 patients with nephrosis, only constant deviation from normal in serum protein was lowering of albumin. Absolute globulin levels remain essentially constant. He expresses his findings as albumin - globulin ratio, and since his report this relative method of expression has become deeply rooted in medical literature. It should be note, however, that when albuminglobulin ratio is thus reverse, reporting

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions

Clinical Information

Plasma proteins are synthesize predominantly in the liver; immunoglobulins are synthesize by mononuclear cells of lymph nodes, spleen and bone marrow. 2 general causes of alterations of serum total protein are change in volume of plasma water and change in concentration of 1 or more of specific proteins in plasma. Of individual serum proteins, albumin is present in such high concentrations that low levels of this protein alone may cause hypoproteinemia. Hemoconcentration results in relative hyperproteinemia; hemodilution results in relative hypoproteinemia. In both situations, concentrations of all individual plasma proteins are affected to the same degree. Hyperproteinemia may be seen in dehydration due to inadequate water intake or to excessive water loss or as result of increased production of proteins. An increase in polyclonal protein production is seen in reactive, inflammatory processes; increased monoclonal protein production is seen in some hematopoietic neoplasms.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions

Interpretation

Table

Electrophoretic zone/regionMajor ProteinsMay be decreased in:May be increased in:
AlbuminAlbuminMalnutrition and malabsorption Kidney disease (nephrotic syndrome) Liver disease Inflammatory conditionsDehydration
Alpha 1Alpha-1 antitrypsin Alpha-1 acid glycoprotein High density lipoprotein (HDL)Alpha-1 antitrypsin deficiency Severe liver diseaseInflammatory diseases
Alpha 2Alpha 2 macroglobulin Ceruloplasmin HaptoglobinMalnutrition Severe liver disease RBC destruction ( hemolysis )Kidney disease (nephrotic syndrome) Acute or chronic inflammatory disease
Beta (1 and 2)Transferrin C3 (component of complement) Low density lipoprotein (LDL) Beta-2 microglobulinMalnutrition Autoimmune diseasesHigh blood cholesterol Iron deficiency anemia Some cases of multiple myeloma or monoclonal gammopathy of unknown significance (MGUS)
GammaAntibodies ( immunoglobulins , IgA, IgG, IgD, IgM, IgE) C-reactive protein (CRP) FibrinogenVariety of genetic immune disorders Secondary immune deficiencyPolyclonal, antibody produced by or derived from different plasma cells : Chronic inflammatory disease Rheumatoid arthritis Lupus Cirrhosis Chronic liver disease Infections Recent immunization Monoclonal, antibody produced by or derived from a single type ( clone ) of plasma cell: Malignancy Multiple myeloma Lymphoma Waldenstrom macroglobulinemia MGUS

Plasma Protein is a collective term for proteins present in the blood. Plasma proteins fall into several different groups and have numerous functions, including maintaining osmotic pressure, and transporting lipids, hormones, vitamins, and minerals. Some plasma proteins are enzymes, while others have functions in blood clotting and the immune system. Excluding immunoglobulins, all major blood proteins are synthesise in the liver. The Total Protein test gives an approximate measure of all plasma protein.S With a typical reference range of 60 - 80 g / l, 1 plasma protein constitutes around 7% of plasma by weight 2 and 0. 5% of total body mass. Serum albumin accounts for around 55% of plasma protein. 3 4 It maintains osmotic pressure of plasma and functions in transport of calcium, lipids, and steroid hormones. Globulins make up approximately 35% of plasma protein. 5 6 Globulins are involved in a range of processes including transport of ions, hormones, and lipids; acute - phase responses; and, as immunoglobulins, immune response. Globulins are divided into four subgroups: 2 alpha, 1 alpha and 2 beta gamma. Fibrinogen is a soluble protein which constitutes around 6. 5% of plasma protein. 7 Conversion of fibrinogen to insoluble Protein fibrin, is a process central to blood clotting. Remaining plasma proteins comprise hundreds of distinct protein molecules. Individually, they are present in small amounts, but together they make up approximately 1% of plasma protein, and have crucial roles as regulatory proteins such as enzymes, proenzymes, and hormones.


Understanding serum protein electrophoresis

When gamma fraction is increase, spike - like monoclonal increase is suggestive of malignant or pre - malignant clonal conditions such as multiple myeloma and Waldenstrom macroglobulinaemia, whereas broader - base, polyclonal increase typically reflects more general inflammatory response. 17 Although monoclonal increase may be of concern, most common cause is monoclonal gammopathy of uncertain significance, which is generally benign but may progress to a malignant condition over time. The most common elevation in gamma globulin levels is polyclonal and typically due to increased immune system activity caused by acute or chronic infection, tissue damage or autoimmune connective tissue diseases such as rheumatoid arthritis, SLE, scleroderma, chronic active autoimmune hepatitis, and primary biliary cholangitis. 9 congenital and acquired immunodeficiency syndromes other conditions associated with reduced immunoglobulin production, such as protein malnutrition conditions causing excessive loss of immunoglobulins, such as sepsis, nephrotic syndrome, burns, and protein - losing enteropathy.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions

What is a globulin test?

Globulins are a group of proteins in your blood. They are made in your liver by your immune system. Globulins play an important role in liver function, blood clotting, and fighting infection. There are four main types of globulins. They are called alpha 1, alpha 2, beta, and gamma. Just as there are different types of globulins, there are different types of globulin tests. These include: total protein test. This blood test measures two types of proteins: globulin and albumin. If protein levels are low, it can mean that you have liver or kidney disease. Serum protein electrophoresis. This blood test measures gamma globulins and other proteins in your blood. It can be used to diagnose a variety of conditions, including disorders of the immune system and a type of cancer called multiple myeloma. Other names for globulin tests: are Serum globulin electrophoresis, total protein

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions

Sources

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions

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