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Serum protein electrophoresis is a laboratory test that examines specific proteins in the blood called globulins. The most common indications for a serum protein electrophoresis test are to diagnose or monitor multiple myeloma, a monoclonal gammopathy of uncertain significance (MGUS), or further investigate a discrepancy between a low albumin and a relatively high total protein. Unexplained bone pain, anemia, proteinuria, chronic kidney disease, and hypercalcemia are also signs of multiple myeloma, and indications for SPE. Blood must first be collected, usually into an airtight vial or syringe. Electrophoresis is a laboratory technique in which the blood serum is applied to either an acetate membrane soaked in a liquid buffer, or to a buffered agarose gel matrix, or into liquid in a capillary tube, and exposed to an electric current to separate the serum protein components into five major fractions by size and electrical charge: serum albumin, alpha-1 globulins, alpha-2 globulins, beta 1 and 2 globulins, and gamma globulins.
Multiple myeloma (MM), also known as plasma cell myeloma and simply myeloma, is a cancer of plasma cells, a type of white blood cell that normally produces antibodies. Often, no symptoms are noticed initially. As it progresses, bone pain, anemia, kidney dysfunction, and infections may occur. Complications may include hypercalcemia and amyloidosis.
Plasma cells, also called plasma B cells or effector B cells, are white blood cells that originate in the lymphoid organs as B cells and secrete large quantities of proteins called antibodies in response to being presented specific substances called antigens. These antibodies are transported from the plasma cells by the blood plasma and the lymphatic system to the site of the target antigen, where they initiate its neutralization or destruction. B cells differentiate into plasma cells that produce antibody molecules closely modeled after the receptors of the precursor B cell.
Hybridoma technology is a method for producing large numbers of identical antibodies. This process starts by injecting a mouse with an antigen that provokes an immune response. A type of white blood cell, the B cell, produces antibodies that bind to the injected antigen. These antibody producing B-cells are then harvested from the mouse and, in turn, fused with immortal myeloma cancer cells, to produce a hybrid cell line called a hybridoma, which has both the antibody-producing ability of the B-cell and the longevity and reproductivity of the myeloma. The hybridomas can be grown in culture, each culture starting with one viable hybridoma cell, producing cultures each of which consists of genetically identical hybridomas which produce one antibody per culture (monoclonal) rather than mixtures of different antibodies (polyclonal). The myeloma cell line that is used in this process is selected for its ability to grow in tissue culture and for an absence of antibody synthesis. In contrast to polyclonal antibodies, which are mixtures of many different antibody molecules, the monoclonal antibodies produced by each hybridoma line are all chemically identical.
POEMS syndrome is a rare paraneoplastic syndrome caused by a clone of aberrant plasma cells. The name POEMS is an acronym for some of the disease's major signs and symptoms, as is PEP.
Cryoglobulinemia is a medical condition in which the blood contains large amounts of pathological cold sensitive antibodies called cryoglobulins – proteins that become insoluble at reduced temperatures. This should be contrasted with cold agglutinins, which cause agglutination of red blood cells.
A precancerous condition is a condition, tumor or lesion involving abnormal cells which are associated with an increased risk of developing into cancer. Clinically, precancerous conditions encompass a variety of abnormal tissues with an increased risk of developing into cancer. Some of the most common precancerous conditions include certain colon polyps, which can progress into colon cancer, monoclonal gammopathy of undetermined significance, which can progress into multiple myeloma or myelodysplastic syndrome. and cervical dysplasia, which can progress into cervical cancer. Bronchial premalignant lesions can progress to squamous cell carcinoma of the lung.
Monoclonal gammopathy of undetermined significance (MGUS) is a plasma cell dyscrasia in which plasma cells or other types of antibody-producing cells secrete a myeloma protein, i.e. an abnormal antibody, into the blood; this abnormal protein is usually found during standard laboratory blood or urine tests. MGUS resembles multiple myeloma and similar diseases, but the levels of antibodies are lower, the number of plasma cells in the bone marrow is lower, and it rarely has symptoms or major problems. However, since MGUS can lead to multiple myeloma, which develops at the rate of about 1.5% a year, or other symptomatic conditions, yearly monitoring is recommended.
Waldenström macroglobulinemia is a type of cancer affecting two types of B cells: lymphoplasmacytoid cells and plasma cells. Both cell types are white blood cells. It is characterized by having high levels of a circulating antibody, immunoglobulin M (IgM), which is made and secreted by the cells involved in the disease. Waldenström macroglobulinemia is an "indolent lymphoma" and a type of lymphoproliferative disease which shares clinical characteristics with the indolent non-Hodgkin lymphomas. It is commonly classified as a form of plasma cell dyscrasia, similar to other plasma cell dyscrasias that, for example, lead to multiple myeloma. Waldenström macroglobulinemia is commonly preceded by two clinically asymptomatic but progressively more pre-malignant phases, IgM monoclonal gammopathy of undetermined significance and smoldering Waldenström macroglobulinemia. The Waldenström macroglobulinemia spectrum of dysplasias differs from other spectrums of plasma cell dyscrasias in that it involves not only aberrant plasma cells but also aberrant lymphoplasmacytoid cells and that it involves IgM while other plasma dyscrasias involve other antibody isoforms.
Plasmacytoma is a plasma cell dyscrasia in which a plasma cell tumour grows within soft tissue or within the axial skeleton.
Monoclonal gammopathy, also known as paraproteinemia, is the presence of excessive amounts of myeloma protein or monoclonal gamma globulin in the blood. It is usually due to an underlying immunoproliferative disorder or hematologic neoplasms, especially multiple myeloma. It is sometimes considered equivalent to plasma cell dyscrasia. The most common form of the disease is monoclonal gammopathy of undetermined significance.
A myeloma protein is an abnormal antibody (immunoglobulin) or a fragment thereof, such as an immunoglobulin light chain, that is produced in excess by an abnormal monoclonal proliferation of plasma cells, typically in multiple myeloma or Monoclonal gammopathy of undetermined significance. Other terms for such a protein are monoclonal protein, M protein, M component, M spike, spike protein, or paraprotein. This proliferation of the myeloma protein has several deleterious effects on the body, including impaired immune function, abnormally high blood viscosity, and kidney damage.
In hematology, plasma cell dyscrasias are a spectrum of progressively more severe monoclonal gammopathies in which a clone or multiple clones of pre-malignant or malignant plasma cells over-produce and secrete into the blood stream a myeloma protein, i.e. an abnormal monoclonal antibody or portion thereof. The exception to this rule is the disorder termed non-secretory multiple myeloma; this disorder is a form of plasma cell dyscrasia in which no myeloma protein is detected in serum or urine of individuals who have clear evidence of an increase in clonal bone marrow plasma cells and/or evidence of clonal plasma cell-mediated tissue injury. Here, a clone of plasma cells refers to group of plasma cells that are abnormal in that they have an identical genetic identity and therefore are descendants of a single genetically distinct ancestor cell.
Plasma cell leukemia (PCL) is a plasma cell dyscrasia, i.e. a disease involving the malignant degeneration of a subtype of white blood cells called plasma cells. It is the terminal stage and most aggressive form of these dyscrasias, constituting 2% to 4% of all cases of plasma cell malignancies. PCL may present as primary plasma cell leukemia, i.e. in patients without prior history of a plasma cell dyscrasia or as secondary plasma cell dyscrasia, i.e. in patients previously diagnosed with a history of its predecessor dyscrasia, multiple myeloma. The two forms of PCL appear to be at least partially distinct from each other. In all cases, however, PCL is an extremely serious, life-threatening, and therapeutically challenging disease.
Monoclonal B-cell lymphocytosis (MBL) is an asymptomatic condition in which individuals have increased blood levels of particular subtypes of monoclonal lymphocytes. This increase must persist for at least 3 months. The lymphocyte subtypes are B-cells that share certain features with the abnormal clones of lymphocytes that circulate in chronic lymphocytic leukemia/small lymphocyte lymphoma (CLL/SLL) or, less frequently, other types of B-cell malignancies. Some individuals with these circulating B-cells develop CLL/SLL or the lymphoma types indicated by their circulating monoclonal B-cells. Hence, MBL is a premalignant disorder
Free light chains (FLCs) are immunoglobulin light chains that are found in the serum (blood) in an unbound (free) state. In recent decades, measuring the amount of free light chains (FLCs) in the blood has become a practical clinical test. FLC tests can be used to diagnose and monitor diseases like multiple myeloma and amyloidosis.
Serum B-cell maturation antigen (sBCMA) is the cleaved form of B-cell maturation antigen (BCMA), found at low levels in the serum of normal patients and generally elevated in patients with multiple myeloma (MM). Changes in sBCMA levels have been found to correlate with a MM patient’s clinical status in response to treatment.
Monoclonal immunoglobulin deposition disease, or MIDD, is a disease characterised by the deposition of monoclonal immunoglobulins on the basement membrane of the kidney. Monoclonal immunoglobulins are produced by monoclonal plasma cells, which are found in a variety of plasma cell dyscrasias. The deposition of monoclonal immunoglobulins on the basement membrane of the kidney causes renal impairment. As well as the kidney, MIDD may also affect the liver, heart, peripheral nerves, lung and skin.
Monoclonal gammopathy of renal significance (MGRS) are a group of kidney disorders that present with kidney damage due to nephrotoxic monoclonal immunoglobulins secreted by clonal plasma cells or B cells. By definition, people with MGRS do not meet criteria for multiple myeloma or other hematologic malignancies. The term MGRS was introduced in 2012 by the International Kidney and Monoclonal Gammopathy Research Group (IKMG). MGRS is associated with monoclonal gammopathy of undetermined significance (MGUS). People with MGUS have a monoclonal gammopathy but does not meet the criteria for the clonal burden nor the presence of end organ damage seen in hematologic malignancies. In a population based study based on the NHANES III health survey; 6% of patients with MGUS were subsequently classified as having MGRS. The prevalence and incidence of MGRS in the general population or in specific populations is not known but it is more prevalent in those over the age of 50 as there is a monoclonal protein (M-protein) present in 3% of those 50 and years older and 5% of those 70 years and older, placing those 50 and older at increased risk of MGRS.
Irene Ghobrial is an American-Egyptian physician who is a professor at the Dana–Farber Cancer Institute and Harvard Medical School, where her research investigates the progression of multiple myeloma. She is interested in why certain patients with monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma develop B cell malignancies. She leads the Stand Up To Cancer multiple myeloma dream team.
References
- ↑ Agarwal, Amit; Ghobrial, Irene M. (1 March 2013). "Monoclonal Gammopathy of Undetermined Significance and Smoldering Multiple Myeloma: A Review of the Current Understanding of Epidemiology, Biology, Risk Stratification, and Management of Myeloma Precursor Disease". Clinical Cancer Research. 19 (5): 985–994. doi:10.1158/1078-0432.ccr-12-2922. PMC 3593941 . PMID 23224402.
- 1 2 Dutta, Ankit K.; Hewett, Duncan R.; Fink, J. Lynn; Grady, John P.; Zannettino, Andrew C. W. (July 2017). "Cutting edge genomics reveal new insights into tumour development, disease progression and therapeutic impacts in multiple myeloma". British Journal of Haematology. 178 (2): 196–208. doi: 10.1111/bjh.14649 . PMID 28466550.
- ↑ van de Donk, Niels W. C. J.; Palumbo, Antonio; Johnsen, Hans Erik; Engelhardt, Monika; Gay, Francesca; Gregersen, Henrik; Hajek, Roman; Kleber, Martina; Ludwig, Heinz; Morgan, Gareth; Musto, Pellegrino; Plesner, Torben; Sezer, Orhan; Terpos, Evangelos; Waage, Anders; Zweegman, Sonja; Einsele, Hermann; Sonneveld, Pieter; Lokhorst, Henk M. (1 June 2014). "The clinical relevance and management of monoclonal gammopathy of undetermined significance and related disorders: recommendations from the European Myeloma Network". Haematologica. 99 (6): 984–996. doi:10.3324/haematol.2013.100552. PMC 4040895 . PMID 24658815.
- ↑ Rajkumar, S Vincent; Dimopoulos, Meletios A; Palumbo, Antonio; Blade, Joan; Merlini, Giampaolo; Mateos, María-Victoria; Kumar, Shaji; Hillengass, Jens; Kastritis, Efstathios; Richardson, Paul; Landgren, Ola; Paiva, Bruno; Dispenzieri, Angela; Weiss, Brendan; LeLeu, Xavier; Zweegman, Sonja; Lonial, Sagar; Rosinol, Laura; Zamagni, Elena; Jagannath, Sundar; Sezer, Orhan; Kristinsson, Sigurdur Y; Caers, Jo; Usmani, Saad Z; Lahuerta, Juan José; Johnsen, Hans Erik; Beksac, Meral; Cavo, Michele; Goldschmidt, Hartmut; Terpos, Evangelos; Kyle, Robert A; Anderson, Kenneth C; Durie, Brian G M; Miguel, Jesus F San (November 2014). "International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma". The Lancet Oncology. 15 (12): e538–e548. doi:10.1016/S1470-2045(14)70442-5. hdl: 2268/174646 . PMID 25439696. S2CID 36384542.
- ↑ Korde, Neha; Kristinsson, Sigurdur Y.; Landgren, Ola (26 May 2011). "Monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM): novel biological insights and development of early treatment strategies". Blood. 117 (21): 5573–5581. doi:10.1182/blood-2011-01-270140. PMC 3316455 . PMID 21441462.
- ↑ Dinarello, Charles A. (7 April 2011). "Interleukin-1 in the pathogenesis and treatment of inflammatory diseases". Blood. 117 (14): 3720–3732. doi:10.1182/blood-2010-07-273417. PMC 3083294 . PMID 21304099.
- ↑ Ballew, Carol; Liu, Kiang; Savage, Peter; Oberman, Albert; Smoak, Carey (January 1990). "The utility of indirect measures of obesity in racial comparisons of blood pressure". Journal of Clinical Epidemiology. 43 (8): 799–804. doi:10.1016/0895-4356(90)90240-p. PMID 2200851.