Diagnosis of Leukemia, Lymphoma, and Myeloma
Tariq I Mughal, John M Goldman, Sabena T Mughal in Understanding Leukemias, Lymphomas, and Myelomas, 2017
Nearly all patients with myeloma have an abnormal protein, known as myeloma protein (M protein), in the blood or urine, or both. This is detected by a technique called protein electrophoresis (Fig. 5.25). Most laboratories use a technique called immunofixation to enhance the results of “standard” protein electrophoresis. Immunofixation gives more rapid results than standard protein electrophoresis, and is more sensitive. In most patients, this is of the subtype IgG, followed by IgA, with rare cases of IgM; IgD and IgE are very rare. It is important to note that many diseases are associated with M proteins. These include benign causes, such as monoclonal gammopathy, also known as monoclonal gammopathy of undetermined significance (MGUS). It is, however, important to monitor all patients with M proteins for a progressive rise, which may herald the emergence of myeloma. It is rarely associated with other cancers arising from the lymphatic system, such as CLL and lymphomas. Typically the levels of the M protein are the highest in patients with myeloma. The increased protein can cause a unique phenomenon in the blood, where the red cells appear to be stacked like coins (rouleaux) (Fig. 5.26).
Multiple Myeloma
Pat Price, Karol Sikora in Treatment of Cancer, 2020
Biochemical screening may show abnormalities of urea, creatinine, calcium, uric acid, total protein, and/or albumin. Serum ALP is usually normal but is commonly raised after a fracture. Electrophoresis of serum and serum free light-chain assay or urine testing in all patients to look for monoclonal light chain is important since patients with Bence Jones–only myeloma have no paraprotein in the serum and patients with a serum paraprotein are at greater risk of renal failure if they also produce Bence Jones protein (BJP). The paraprotein in the serum and/or urine is then confirmed and typed by immunofixation. The paraprotein is of IgG subtype in 55–60% of cases and IgA in 20–25%, of whom two-thirds also have BJP in the urine and 95% have a clonal serum free light chain. Rarely, the paraprotein may be of IgD, IgE, or IgM type. Overall two-thirds of paraproteins have kappa light chains and one-third lambda. Twenty percent of cases are Bence Jones–only myeloma. In less than 1% of patients, no paraprotein is detectable in either serum or urine (non-secretory myeloma).
Diagnostic applications of immunology
Gabriel Virella in Medical Immunology, 2019
Immunofixation (immunoblotting) is a multistep process (Figure 15.2). In the first step, several aliquots of the patient's serum are simultaneously separated by electrophoresis. One of the separation lanes is stained as reference for the position of the different serum proteins (extreme right lane in the figure), while paper strips embedded with different antibodies are laid over the remaining separation lanes. The antibodies diffuse into the agar and react with the corresponding immunoglobulins. After washing off unbound immunoglobulins and antibodies, the lanes where immunofixation take place are stained, revealing whether the antisera did or did not recognize the proteins they are directed against. In this example, a monoclonal protein reacting with anti-IgG and anti-λ antisera was revealed. This test is useful in diagnosing myeloma, macroglobulinemia of Waldenström, and other plasma cell dyscrasias where the detection and characterization of a monoclonal gammopathy are essential for the diagnosis.
A case report: anti-NMDA receptor encephalitis
Published in Journal of Community Hospital Internal Medicine Perspectives, 2018
Pavan Bhat, Ameer Ahmed, Preetam Jolepalem, Charmian Sittambalam
Current diagnosis is based upon finding anti-NMDAR antibodies in the CSF or serum. CSF studies show lymphocytic pleocytosis and normal to mild elevation of protein. Oligoclonal bands may be present in 60% of patients [6]. Although there is controversy between testing for serum or CSF antibody titers, CSF titers generally appear to correlate with disease activity [4,5]. The CSF antibody has been found to be more sensitive but there are still some explanations for why one might find a falsely negative result. This may include smaller quantities of antibodies produced, antigen denaturation during tissue-based immunofixation and variability between human and mouse epitopes used in analysis. In our patient, serum titers were negative as were CSF antibody titers, which is atypical, but given her characteristic neuropsychiatric dysfunction with rapid symptom resolution after ovarian teratoma removal, a presumptive diagnosis of anti-NMDAR encephalitis fit the bill.
Applications of MALDI-TOF mass spectrometry in clinical proteomics
Published in Expert Review of Proteomics, 2018
Viviana Greco, Cristian Piras, Luisa Pieroni, Maurizio Ronci, Lorenza Putignani, Paola Roncada, Andrea Urbani
The evaluation of the effectiveness of chemotherapy in hematological disorders, such as leukemia and multiple myeloma, is carried out by estimating the so-called MRD. This is generally based on an evaluation of the monoclonal components that circulate in patients’ blood using nephelometry and immunofixation. However, this historical technology is not able to discriminate circulating monoclonal immunoglobulins resulting from malignancy from recombinant biopharmaceutical products used for the therapeutic approach. Large efforts have been undertaken by numerous scientific groups in order to establish sensitive and effective assessment criteria, which are, above all, capable of providing acceptable and easily repeatable results worldwide. Serological values, such as serum‐free light chain, or immunophenotypic tools on bone marrow or peripheral blood, such as multi‐parameter flow cytometry and next‐generation/high‐throughput sequencing technologies (NGS) have been widely proposed. Each immunoglobulin is characterized by a unique sequence of amino acids whose unique mass can be used as marker to monitor patient disease overtime. The precise evaluation of their levels provides prognostic information and a detailed report of treatments outcome [129].
CD38-targeting antibodies in multiple myeloma: mechanisms of action and clinical experience
Published in Expert Review of Clinical Immunology, 2018
Kristine A. Frerichs, Noemi Anna Nagy, Pieter L. Lindenbergh, Patty Bosman, Jhon Marin Soto, Marloes Broekmans, Richard W. J. Groen, Maria Themeli, Louise Nieuwenhuis, Claudia Stege, Inger S. Nijhof, Tuna Mutis, Sonja Zweegman, Henk M. Lokhorst, Niels W. C. J. van de Donk
MM cells produce a monoclonal immunoglobulin (M-protein), which is monitored by using serum protein electrophoresis and immunofixation electrophoresis (IFE) to assess response to treatment. Therefore, all therapeutic antibodies may interfere with the detection and monitoring process of M-protein levels in the serum of patients [81]. Daratumumab (IgG1-κ isotype) interference with the IFE assay is most likely in patients with an IgG-κ M-protein as this protein may comigrate with daratumumab [82–84]. In that situation, the two bands cannot be differentiated from each other without extra tests such as the daratumumab-specific IFE reflex assay (DIRA). In the DIRA assay, an anti-daratumumab antibody binds to daratumumab which alters its migration pattern to distinguish endogenous M-protein from therapeutic antibody [82,84]. To avoid interference of the therapeutic antibody with laboratory results, it is also important to inform the laboratory staff that patients are receiving daratumumab treatment or other antibody therapy.
Related Knowledge Centers
- Antibody
- Monoclonal Antibody
- Protein
- Urine
- Waldenstrom Macroglobulinemia
- Multiple Myeloma
- Serum
- Antigen
- Electrophoresis
- Waldenström Macroglobulinemia
- Gel Electrophoresis of Proteins