Several subsets of serum protein electrophoresis are available. Once the serum samples are run on the analyzer, a technologist compares the curves with patients previous results and ensures the fractions are appropriately delineated. The M protein has an incomplete heavy chain and no light chain. Multiple Myeloma. [13, 14], Diagnosis of plasma cell dyscrasias It's easier to check your kidney health at home now more than ever. Fortunately, the cause of an abnormal curve is not always pathologic. Peaks and valleys in the bands may mean that you may be making too many or too few of certain proteins. Bird J, Behrens J, Westin J, et al. Rarely, plasma cells can enter into the circulation and if they represent 20 percent or more of the blood cells, the condition is called plasma cell leukemia. Note that the percent of plasma cells in the bone marrow, assessed by flow cytometry, is not the value used in the diagnostic criteria above. When there is damage to the kidneys, other proteins, such as albumin, may also be present in the urine. Serum protein bands (monoclonal gammopathy) will sometimes be found following serum protein electrophoresis in patients presenting with classic signs or symptoms of multiple myeloma, e.g. Some immunoglobulins can be abnormal and may be due to cancer. How is an immunofixation test interpreted? All Rights Reserved. Autoinflammatory vs. Autoimmune: What is the Difference? Merck Manual Professional Version. It may also depend on the unique patterns made by the proteins. Monoclonal gammopathy of undetermined significance (MGUS). Monoclonal Proteins (M Proteins) | Myeloma Center Monoclonal Immunoglobulin (Ig), Monoclonal antibody, Immunofixation This website also contains material copyrighted by 3rd parties. Save my name, email, and website in this browser for the next time I comment. Immunoglobulins, known as Igs, are a group of proteins that help protect your body from illness. The subsets of these proteins and their relative quantity are the primary focus of the interpretation of serum protein electrophoresis.1,3. ; 2014 Mar 14 [cited 2020 Jan 22]; [about 3 screens]. M-Protein Antibodies and Significance in Blood - Verywell Health High blood protein When to see a doctor - Mayo Clinic In some patients, the myeloma cells do not make a complete monoclonal immunoglobulin molecule with two heavy and two light chains. Red top tube for the collection of serum used. There are two main types of proteins in the blood: albumin and globulin. Symptoms of malnutrition or malabsorption include: A health care professional will take a blood sample from a vein in your arm, using a small needle. https://www.merckmanuals.com/professional/hematology-and-oncology/plasma-cell-disorders/monoclonal-gammopathy-of-undetermined-significance-mgus?query=mgus. https://www.uptodate.com/contents/search. In addition, doctors stagemyeloma to help them decide on the best treatmentplan. Common causes of high levels include: Low protein levels may be caused by many conditions. National Multiple Sclerosis Society; MS Symptoms; [cited 2019 Dec 18]; [about 3 screens]. URL of this page: https://medlineplus.gov/lab-tests/immunofixation-ife-blood-test/. What does "polyclonal light chains detected but no monoclonal immunoglobilin or free light chain (bencejones) is MD presence of free light chain in urine is diagnostic of multiple myeloma.Multiple myeloma is a type of cancer that is caused by malignant plasma cells that proliferate in the bone marrow and produce abnormally high amounts. Pathol Biol (Paris). Electrophoresis separates proteins based on their physical properties, and the subsets of these proteins are used in interpreting the results. The Licensed Content is the property of and copyrighted by DSM. If there are not CRAB signs and/or symptoms, 60% plasma cells in the bone marrow indicates a diagnosis. Medscape Drugs & Diseases. Globulins comprise a much smaller fraction of the total serum protein content. We look forward to connecting with you. 2015 May. Multiple Myeloma: Symptoms and Signs; 2016 Oct [cited 2019 Dec 10]; [about 3 screens]. Medscape Education, 20022007195-overviewDiseases & Conditions, encoded search term (Immunofixation) and Immunofixation, Fast Five Quiz: Key Aspects of Multiple Myeloma, Fast Five Quiz: Multiple Myeloma Management, Fast Five Quiz: Relapsed/Refractory Multiple Myeloma, From War-Torn Beirut to Myeloma Research in NY, Bispecific Antibody Provides Durable Remission in Myeloma, Pathology of Mantle Cell Lymphoma: Biopsies, Diagnostic Markers, and Options for Clinicians Treating This Disease, CAR T-Cell Therapy for Relapsed/Refractory Multiple Myeloma. NGS can identify mutations present in the genes of the myeloma cells. M Protein (Myeloma Protein): Definition, Test, and Levels - WebMD Washington D.C.: American Association for Clinical Chemistry; c20012019. The next most common type is light chain myeloma in which no intact immunoglobulin is produced. When excreted in large amounts, Bence Jones proteins (free light chains) can sometimes make the urine appear foamy and they can cause injury to the kidneys. Guido Tricot. When a narrow band with sharp borders can be identified, it implies the presence of a monoclonal protein (see image below). Monoclonal gammopathies are associated with a clonal process that is malignant or potentially malignant, including multiple myeloma, Waldenstrms macroglobulinemia, solitary plasmacytoma, smoldering multiple myeloma, monoclonal gammopathy of undetermined significance, plasma cell leukemia, heavy chain disease, and amyloidosis. In other cases, patients may have non-specific symptoms, meaning the discovery of a protein band in the serum . There are five types of heavy chains, and each type is represented by a specific letter: IgG, IgA, IgD, IgE and IgM. Available from: Lab Tests Online [Internet]. Blood appears to be a single substance to the naked eye. A serum thyroxine-binding globulin (TBG) level test is a blood test that measures the amount of TBG in your blood. A second screen is used to confirm positive test results. If you have questions about your results, talk to your health care provider. Serum protein electrophoresis (SPEP) and urine protein electrophoresis (UPEP) are tests in which proteins in blood and urine samples are separated so that individual antibodies can be identified and quantified. Monoclonal gammopathy of undetermined significance. Evidence of end-organ damage as defined by the CRAB criteria. These symptoms could include the following: Some of the conditions that could be causing these symptoms are: No preparation is needed for the test. 2010. In blood cancers such as myeloma, the 'M' in 'M protein' stands for monoclonal. John C Leighton, Jr, MD, FACP is a member of the following medical societies: American College of Physicians, American Medical Association, American Society of Hematology, American Society of Clinical OncologyDisclosure: Nothing to disclose. Myelomacells produce many copies of its anibody. Typically present in low amounts, conditions such as multiple myeloma and Waldenstrms macroglobulinemia show proliferation of abnormal or cancerous plasma cells. SPEP and UPEP don't measure myeloma cells; they measure the output of myeloma cells. The albumin level is decreased under circumstances in which there is less production of the protein by the liver or in which there is increased loss or degradation of this protein. Protein Electrophoresis Serum Test - Healthline How is a serum sample collected for an immunofixation test? Hematology: Basic Principles and Practice. M protein is an abnormal protein caused by plasma cells. If the result is negative, it is safe to conclude that a pure kappa or lambda light chain is present. Available from: https://ufhealth.org/protein-electrophoresis-serum. Other inflammatory conditions of the CNS can present with oligoclonal bands in CSF resulting from intrathecal production of antibodies. The albumin band represents the largest protein component of human serum. Because MGUS is not harmful, it doesn't need to be treated. Monoclonal bands are usually seen in the zone but may be seen in proximity of the band or, rarely, in the 2 region. A negative urine or serum immunofixation result does not always rule out a plasma cell dyscrasia, as a nonsecretory or oligosecretory multiple myeloma can present with a negative immunofixation finding in both the urine and the serum. [14], Mass spectrometry is sometimes employed in place of immunofixation because of the latters limitations, such as in the detection of low-level disease. All of these measurements provide information about the extent of the disease and are useful for monitoring response to treatment. All material on this website is protected by copyright, Copyright 1994-2023 by WebMD LLC. Monoclonal gammopathy of undetermined significance (MGUS) care at Mayo Clinic. Many subspecialists. If serum protein electrophoresis is abnormal at any time during the follow-up, a referral should be made. excess of an abnormal immunoglobulin called monoclonal protein (or M protein). There may be some slight bruising afterward. Once a monoclonal gammopathy has been identified and a particular plasma cell proliferative disorder has been diagnosed, the quantification of the monoclonal protein is a good surrogate marker for monitoring the . Affected patients have no M protein in their urine, no lytic bone lesions, no anemia, no hypercalcemia, and no renal disease. Immunofixation consists of an electrophoresis phase and a fixation phase. The most common condition linked with these abnormal proteins is MGUS. See why Myeloma protein might show up in your blood and what kinds of conditions it might be a sign of. Monoclonal gammopathies of undetermined significance. Reference Range Immunofixation consists of an electrophoresis phase and a fixation phase. Electrophoresis describes the migration of charged particles in an electric field, and their subsequent separation based on size and charge. IgA or IgM bands are less common. Ceruloplasmin, alpha2-macroglobulin, and haptoglobin contribute to the alpha2-protein band. On the contrary, a persistent monoclonal protein despite treatment is a sign of refractory disease. Keywords: bone marrow; monoclonal protein; multiple myeloma; protein electrophoresis; serum free light chains. Both of the following criteria must be met: In healthy individuals, plasma cellsproduce proteins called polyclonal immunoglobulins. These are a collection of antibodies that protect the body against all kinds of different invading viruses, bacteria or other infectious agents (antigens). Sometimes a CBC with differential (CBC with diff), a test that also measures the number of the different types of white blood cells present in the blood, is ordered. Proteins play many important roles, including providing energy for the body, rebuilding muscles, and supporting the immune system. The method can be used to examine specific proteins in the blood, urine, and other body fluids. High amounts of M protein in a person's blood or urine may be a sign they have multiple myeloma but the presence of M proteins could also indicate other types of plasma cell tumors. Cytogenetic Analysis. This abnormal protein is formed within your bone marrow, the soft, blood-producing tissue that fills in the center of most of your bones. Serum protein electrophoresis (SPEP) is a laboratory technique thats used to determine the levels of some types of proteins in a blood sample. Characteristic differentiating features of the monoclonal gammopathies are listed in Table 4.7, In some patients with a plasma cell dyscrasia, serum protein electrophoresis may be normal because the complete monoclonal immunoglobulin is absent or is present at a very low level.7 In one series,6 serum protein electrophoresis showed a spike or localized band in only 82 percent of patients with multiple myeloma. Youve read {{metering-count}} of {{metering-total}} articles this month. If the curve is relatively normal (e.g. Measuring M-Protein SPEP, UPEP Tests | Int'l Myeloma Fdn Typically, the monoclonal protein is discovered, and workup then ensues. Again, the lanes are broad and the transition to the lane borders is smooth. The presence of a suspected monoclonal can lead to further testing by immunofixation electrophoresis (IFE). Further separation of protein subtypes is achieved by staining with an immunologically active agent, which results in immunofluorescence and immunofixation. Consequently, urine protein electrophoresis is recommended in all patients suspected of having a plasma cell dyscrasia.10. Bone Marrow Tests. This test measures the numbers of red blood cells, white blood cells and platelets in the blood. Eric B Staros, MD is a member of the following medical societies: American Medical Association, American Society for Clinical Pathology, Association for Molecular Pathology, College of American PathologistsDisclosure: Nothing to disclose. In healthy individuals, antibodies produced by plasma cells in the bone marrow help this process. You can also contact us directly if you need to. BCIT students get their phlebotomy competencies signed off during a two-week placement in Level 1, so whether you collect blood during the long block practicum is very much dependent on the practicum site. Blood Cancer J. The LLS mission: Cure leukemia, lymphoma, Hodgkin's disease and myeloma, and improve the quality of life of patients and their families. Suspected multiple myeloma, Waldenstrms macroglobulinemia, primary amyloidosis, or related disorder, Unexplained peripheral neuropathy (not attributed to longstanding diabetes mellitus, toxin exposure, chemotherapy, etc. Abnormal levels of certain chemicals may indicate that an organ is not working properly or they may be caused by cancer or other health conditions. The proteins create separate bands on the gel, which are then analyzed by the laboratory. In a normal result, the lanes are broad and there is a gradual and smooth reduction in the color density toward the edges of the lane with no narrow dense band with sharp borders identified within the lane. [12] an additional assay for the identification of IgD or IgE must be performed. Diagnosis of monoclonal gammopathy of undetermined significance. 2023 Healthline Media LLC. Immunofixation: Reference Range, Interpretation, Collection and Panels The identification of a monoclonal gammopathy depends on serum and urine protein electrophoresis and immunoelectrophoresis (IFE) 1 and/or quantitative free light chain assays. Immunofixation to identify the M component as an IgM immunoglobulin with a quantitative IgM level greater than 3 g/dL. The serum immunofixation test is most often done with a blood sample. Rochester, Minn.: Mayo Foundation for Medical Education and Research; 2019. Br J Haematol. Gainesville (FL): University of Florida Health; c2021. 2016 Jan 27 [cited 2019 Dec 18]; 2016 (1):37-51. [10]. It should be noted that immunoglobulins often can be found throughout the electrophoretic spectrum. Malabsorption; [updated 2019 Nov 11; cited 2019 Dec 10]; [about 2 screens]. Tests are done to measure the levels of many different substances in the blood. [2] : Monoclonal gammopathy of undetermined significance (MGUS) Immunofixation "fixes" certain proteins into place with antibodies and then washes away the others before staining them. Dimopoulos M, Kyle R, Fermand JP, et al. Accessed April 18, 2019. [QxMD MEDLINE Link]. Your use of this website constitutes acceptance of Haymarket Medias Privacy Policy and Terms & Conditions. In most cases in which a monoclonal protein is present, it shows as a narrow band at the IgG lane in combination with a monoclonal band at the kappa or lambda lane. Monoclonal gammopathy of undetermined significance (MGUS) and smoldering (asymptomatic) multiple myeloma: IMWG consensus perspectives risk factors for progression and guidelines for monitoring and management. Murray DL, Puig N, Kristinsson S, et al. 11 (2):24. The gamma-globulin zone is decreased in hypogammaglobulinemia and agammaglobulinemia. Among these other causes are Waldenstrms macroglobulinemia, solitary plasmacytoma, smoldering multiple myeloma, monoclonal gammopathy of undetermined significance, plasma cell leukemia, heavy chain disease, and amyloidosis.4,7, The quantity of M protein can help differentiate multiple myeloma from monoclonal gammopathy of undetermined significance. The Leukemia & Lymphoma Society is a 501(c)(3) organization, and all monetary donations are tax deductible to the fullest extent allowed by tax laws. Serum protein electrophoresis is a laboratory examination that commonly is used to identify patients with multiple myeloma and other disorders of serum protein. Its not always obvious what high or low protein levels in the blood serum may mean. Ronald Hoffman, Leslie E. Silberstein, Sanford J. Shattil, Bruce Furie, Philip McGlave. Mayo Clinic does not endorse companies or products. MGUS usually causes no problems. An apparent monoclonal protein on serum protein electrophoresis may or may not be a true monoclonal protein. What is the clinical application of an immunofixation test? Bethesda (MD): U.S. Department of Health and Human Services; NCI Dictionary of Cancer Terms: multiple myeloma; [cited 2019 Dec 10]; [about 3 screens]. Chromosomal abnormalities play a crucial role in identifying cancerous cells and determining the risk of relapse. Plasma cell disorders. Instead, its used along with other laboratory tests to provide more information to help with diagnosis. document.getElementById( "ak_js_1" ).setAttribute( "value", ( new Date() ).getTime() ); Is there something going on we should know about? A small number of patients with myeloma have either oligosecretory disease, inwhich the detectable level of monoclonal protein is low, or nonsecretory disease,in which no monoclonal protein can be detected. correct number of peaks and protein values), the analyzer does a pretty good job of identifying each fraction. Evol Med Public Health. A doctor may use the results to make a diagnosis or decide on a course of treatment. Burns also may result in a low albumin level. Your doctor may also order more tests. That criteria is determined by a pathologist who reviews the bone marrow aspirate slides. Less than 10% plasma cells are present in bone marrow, and patients have no lytic bony lesions, anemia, hypercalcemia, or renal insufficiency. Blood Chemistry Tests. High protein levels may be caused by many conditions. If you log out, you will be required to enter your username and password the next time you visit. The alpha1-protein fraction is comprised of alpha1-antitrypsin, thyroid-binding globulin, and transcortin. If these examinations are normal, serum protein electrophoresis should be repeated in three to six months; if that examination is normal, serum protein electrophoresis should be repeated annually. [20]. Please confirm that you would like to log out of Medscape. 2019 Jun 20. 2018 Dec 3. A polyclonal immunoglobulin pattern in the serum or urine immunofixation is considered to be nonspecific. Available from: National Cancer Institute [Internet]. The test may also be performed again in the future. The examination also should be considered in other red flag situations (Table 1).24, If the examination is normal but multiple myeloma, Waldenstrms macroglobulinemia, primary amyloidosis, or a related disorder still is suspected, immunofixation also should be performed because this technique may be more sensitive in identifying a small monoclonal (M) protein.5. See permissionsforcopyrightquestions and/or permission requests. Waldenstrom macroglobulinemia always shows a serum IgM-type monoclonal band. Serum is placed on a specific medium, and a charge is applied. Immunofixation tests can also be done in urine. Immunofixationconsists of an electrophoresis phase and a fixation phase. Rajhumar SV. [Full Text]. The names of these subsets are based on the method that is used to separate and differentiate the various serum components. Then it says: "The SPE pattern appears essentially unremarkable. The IFX test can also be used to study changes in the structure of normal. 2009. Serum protein electrophoresis (SPEP) is a test that measures theantibodies in the blood and can find a monoclonal antibody. The precise cause of MGUS isn't known. Levels of albumin are increased in patients with a relative reduction in serum water (e.g., dehydration). A homogeneous immunoglobulin resulting from the proliferation of a single clone of plasma cells that; during electrophoresis of serum, appears as a narrow band or "spike"; it is characterized by heavy chains of a single class and subclass, and light chains of a single type. Serum Protein Electrophoresis (SPEP) Test; [cited 2021 Aug 9]; [about 3 screens]. Definitive diagnosis of multiple myeloma requires 10 to 15 percent plasma cell involvement as determined by bone marrow biopsy. The most common type of myeloma is IgG kappa, occurring in approximately 52 % of patients. Finally, the sample is washed to remove the proteins that do not precipitate and then stained, destained, and dried. Available from: Hinkle J, Cheever K. Brunner & Suddarth's Handbook of Laboratory and Diagnostic Tests. An immunofixation blood test, also known as protein electrophoresis, measures certain proteins in the blood. [QxMD MEDLINE Link]. The peaks for these components lie toward the negative electrode, with the gamma peak being closest to that electrode. Visual examination of electrophoretic patterns by a pathologist is the most sensitive method of detecting monoclonal proteins since small bands may be obscured in densitometric scans. 2021 Feb 1. All rights reserved. In these cases of light chain myeloma, serum test results may not show the characteristic increase of M protein (M spike), but there may be large amounts of monoclonal light chains in the urine. Health Encyclopedia - University of Rochester Medical Center A malignant plasma cell is called a . The article also provides a simple guide to result interpretation and suggestions on follow-up of abnormal results. What is the reference range of an immunofixation test? Eric B Staros, MD Associate Professor of Pathology, St Louis University School of Medicine; Director of Clinical Laboratories, Director of Cytopathology, Department of Pathology, St Louis University Hospital An immunofixation blood test, also known as protein electrophoresis, measures certain proteins in the blood. These include an elevated protein level, anemia and abnormalities in kidney function or calcium levels. Obtaining a precise diagnosis will help the doctor to: The results of blood tests that accompany periodic medical examinations may indicate the need for further evaluation for myeloma. The various proteins in the body perform different functions. Your doctor may recommend SPEP if you are experiencing symptoms of a condition affecting the proteins in your blood serum. When the whole immunoglobulin is present in the urine, it is usually at a low level. Immunofixation reveals the heavy chain as alpha, gamma, or mu. Bone marrow biopsy may be useful to show aggregates of plasma cells in focal or diffuse patterns. Pruthi RK (expert opinion). Given the dismal impact on prognosis in the latter scenario, To use the sharing features on this page, please enable JavaScript. Keep in mind that these are just clues. Copyright 2005 by the American Academy of Family Physicians. Monoclonal gammopathies are conditions in which abnormal proteins are found in the blood. Tax Identification Number: 13-5644916, Myeloma Guide: Information for Patients and Caregivers, A bone marrow aspirationto remove a liquid marrow sample, A bone marrow biopsyto remove a small amount of bone filled with marrow, Malignant plasma cells: Plasma cell level of >10% in a bone marrow biopsy sample, Unusually large amounts of monoclonal protein (called an M spike). If the monoclonal protein level decreases or is undetectable after chemotherapy, it might indicate a response to treatment. Next-generation sequencing is being done now on a research basis but may soon be used in routine clinical practice. Copyright 2017, 2013 Decision Support in Medicine, LLC. [Internet]. The speed of movement is dictated by their charge. Alexandria (VA): American Society of Clinical Oncology; 20052019. Healthline has strict sourcing guidelines and relies on peer-reviewed studies, academic research institutions, and medical associations. Urine immunoelectrophoresis is a lab test that measures immunoglobulins in a urine sample. Efficacy and outcome of autologous transplantation in rare myelomas. No abstract available. Immunofixation is clearly indicated upon clinical or laboratory evidence of a plasma cell dyscrasia for the diagnosis of multiple myeloma, Waldenstrom macroglobulinemia, or amyloid light-chain (AL) amyloidosis. A decreased alpha1-protein band may occur because of alpha1-antitrypsin deficiency or decreased production of the globulin as a result of liver disease. Polyclonal Gammopathy: Definition & Causes - Cleveland Clinic In many myeloma patients, the coordinated process of making and attaching light chains and heavy chains fails in the malignant plasma cells. Immune Thrombocytopenia Purpura (ITP): What helps? The output of monoclonal protein can vary from patient to patient. A serum free light chain ratio is indicated in the case of a negative immunofixation result when the suspicion for multiple myeloma is still high. The released hemoglobin can also bind to haptoglobin, a protein in the 2 fraction, forming a hemoglobin-haptoglobin complex that blurs the 2 and separation and may resemble a malignant peak. In zone electrophoresis, for example, different protein subtypes are placed in separate physical locations on a gel made from agar, cellulose, or other plant material.2,3 The proteins are stained, and their densities are calculated electronically to provide graphical data on the absolute and relative amounts of the various proteins. This is a broad term encompassing a number of modern technologies that increase the speed and reduce the cost of DNA sequencing to look for mutations. Please check with your financial advisor if you have more questions. Monoclonal gammopathy of undetermined significance (MGUS) is a condition in which an abnormal protein known as monoclonal protein or M protein is in your blood. Role of urine immunofixation in the complete response assessment of MM patients other than light-chain-only disease. Much of the clinical interest is focused on the gamma region of the serum protein spectrum because immunoglobulins migrate to this region. Immunoglobulins are secreted by plasma cells, a type of white blood cell in the bone marrow, in response to infection and disease. 24:1121-7. Anemia, pancytopenia, hypercalcemia, and renal disease may be present. PDF Multiple Myeloma Early Detection, Diagnosis, and Staging This article provides a comprehensive review of serum protein electrophoresis, including a discussion of how the examination is performed, what it measures, and when it is indicated. [10], Primary screening for plasma cell dyscrasias, No studies have addressed the role of serum or urine immunofixation in screening of the general population for multiple myeloma and related disorders. This process is known as electrophoresis. [ 1] Serum or urine immunofixation negative for a monoclonal protein or a polyclonal pattern is. 2015 Oct. 47 (6):564-9. Continuing Medical Education (CME/CE) Courses. Fluorescence in situ hybridization (FISH) is a type of laboratory test that uses special dyes to identify mutations of specific chromosomes in cells. Peripheral blood smear often shows RBC aggregates in a rouleaux formation. Monoclonal Protein on Serum Protein Electrophoresis (M Component) Finally, isolated light chain bands, either kappa or lambda, represent more commonly pure kappa or lambda light chain gammopathies or, less commonly, immunoglobulin D (IgD) or immunoglobulin E (IgE) gammopathies. The identification of a monoclonal immunoglobulin is helpful in the diagnosis of the following conditions If the sample is hemolyzed in vitro (red blood cells are ruptured outside the body such as during traumatic blood draw), there will be free hemoglobin, which migrates to the 1 fraction.