CASE REPORT a Case of Multiple Myeloma with Unusual Serum
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International Myeloma Working Group Guidelines for the Management Of
Leukemia (2009) 23, 1716–1730 & 2009 Macmillan Publishers Limited All rights reserved 0887-6924/09 $32.00 www.nature.com/leu REVIEW International Myeloma Working Group guidelines for the management of multiple myeloma patients ineligible for standard high-dose chemotherapy with autologous stem cell transplantation A Palumbo1, O Sezer2, R Kyle3, JS Miguel4, RZ Orlowski5, P Moreau6, R Niesvizky7, G Morgan8, R Comenzo9, P Sonneveld10, S Kumar3, R Hajek11, S Giralt5, S Bringhen1, KC Anderson12, PG Richardson12, M Cavo13, F Davies8, J Blade´14, H Einsele15, MA Dimopoulos16, A Spencer17, A Dispenzieri3, T Reiman18, K Shimizu19, JH Lee20, M Attal21,22, M Boccadoro1, M Mateos4, W Chen23,24, H Ludwig25, D Joshua26, J Chim27, V Hungria28, I Turesson29, BGM Durie30 and S Lonial31 on behalf of the IMWGn 1Divisione di Ematologia dell’Universita` di Torino, Azienda Ospedaliera S. Giovanni Battista, Ospedale Molinette, Torino, Italy; 2Department of Hematology/Oncology, Charite´–Universitaetsmedizin Berlin, Germany; 3Division of Hematology, Mayo Clinic, Rochester, Minnesota, USA; 4Servicio de Hematologı´a, Hospital Universitario de Salamanca. CIC, IBMCC (USAL-CSIC), Salamanca, Spain; 5Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA; 6Department of Clinical Hematology, University Hospital, Nantes, France; 7Center for Lymphoma and Myeloma, Weill Medical College of Cornell University, New York, New York, USA; 8Institute of Cancer Research, Royal Marsden Hospital, London, UK; 9Blood Bank and Stem Cell -
Defining Natural Antibodies
PERSPECTIVE published: 26 July 2017 doi: 10.3389/fimmu.2017.00872 Defining Natural Antibodies Nichol E. Holodick1*, Nely Rodríguez-Zhurbenko2 and Ana María Hernández2* 1 Department of Biomedical Sciences, Center for Immunobiology, Western Michigan University Homer Stryker M.D. School of Medicine, Kalamazoo, MI, United States, 2 Natural Antibodies Group, Tumor Immunology Division, Center of Molecular Immunology, Havana, Cuba The traditional definition of natural antibodies (NAbs) states that these antibodies are present prior to the body encountering cognate antigen, providing a first line of defense against infection thereby, allowing time for a specific antibody response to be mounted. The literature has a seemingly common definition of NAbs; however, as our knowledge of antibodies and B cells is refined, re-evaluation of the common definition of NAbs may be required. Defining NAbs becomes important as the function of NAb production is used to define B cell subsets (1) and as these important molecules are shown to play numerous roles in the immune system (Figure 1). Herein, we aim to briefly summarize our current knowledge of NAbs in the context of initiating a discussion within the field of how such an important and multifaceted group of molecules should be defined. Edited by: Keywords: natural antibody, antibodies, natural antibody repertoire, B-1 cells, B cell subsets, B cells Harry W. Schroeder, University of Alabama at Birmingham, United States NATURAL ANTIBODY (NAb) PRODUCING CELLS Reviewed by: Andre M. Vale, Both murine and human NAbs have been discussed in detail since the late 1960s (2, 3); however, Federal University of Rio cells producing NAbs were not identified until 1983 in the murine system (4, 5). -
Multiple Myeloma Baseline Immunoglobulin G Level and Pneumococcal Vaccination Antibody Response
Journal of Patient-Centered Research and Reviews Volume 4 Issue 3 Article 5 8-10-2017 Multiple Myeloma Baseline Immunoglobulin G Level and Pneumococcal Vaccination Antibody Response Michael A. Thompson Martin K. Oaks Maharaj Singh Karen M. Michel Michael P. Mullane Husam S. Tarawneh Angi Kraut Kayla J. Hamm Follow this and additional works at: https://aurora.org/jpcrr Part of the Immune System Diseases Commons, Medical Immunology Commons, Neoplasms Commons, Oncology Commons, Public Health Education and Promotion Commons, and the Respiratory Tract Diseases Commons Recommended Citation Thompson MA, Oaks MK, Singh M, Michel KM, Mullane MP, Tarawneh HS, Kraut A, Hamm KJ. Multiple myeloma baseline immunoglobulin G level and pneumococcal vaccination antibody response. J Patient Cent Res Rev. 2017;4:131-5. doi: 10.17294/2330-0698.1453 Published quarterly by Midwest-based health system Advocate Aurora Health and indexed in PubMed Central, the Journal of Patient-Centered Research and Reviews (JPCRR) is an open access, peer-reviewed medical journal focused on disseminating scholarly works devoted to improving patient-centered care practices, health outcomes, and the patient experience. BRIEF REPORT Multiple Myeloma Baseline Immunoglobulin G Level and Pneumococcal Vaccination Antibody Response Michael A. Thompson, MD, PhD,1,3 Martin K. Oaks, PhD,2 Maharaj Singh, PhD,1 Karen M. Michel, BS,1 Michael P. Mullane,3 MD, Husam S. Tarawneh, MD,3 Angi Kraut, RN, BSN, OCN,1 Kayla J. Hamm, BSN3 1Aurora Research Institute, Aurora Health Care, Milwaukee, WI; 2Transplant Research Laboratory, Aurora St. Luke’s Medical Center, Aurora Health Care, Milwaukee, WI; 3Aurora Cancer Care, Aurora Health Care, Milwaukee, WI Abstract Infections are a major cause of morbidity and mortality in multiple myeloma (MM), a cancer of the immune system. -
A Case of Aggressive Multiple Myeloma with Cleaved, Multilobated, and Monocytoid Nuclei, and No Serum Monoclonal Gammopathy
Annals o f Clinical & Laboratory Science, vol. 30, no. 3, 2000 283 A Case of Aggressive Multiple Myeloma with Cleaved, Multilobated, and Monocytoid Nuclei, and No Serum Monoclonal Gammopathy Y. Albert Yeh, Alex A. Pappas, James T. Flick, and Anthony W. Butch* Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, Arkansas (^Current address: Department of Pathology and Laboratory Medicine, UCLA Medical Center, Los Angeles, CA) Abstract Multiple myeloma is a B-cell malignancy characterized by proliferation of neoplastic plasma cells. A few cases have been reported identifying variant forms of neoplastic plasma cells with atypical nuclei that secrete myeloma protein. We report a highly unusual case of plasma cell myeloma that presented with cleaved, multilobated, and monocytoid nuclei, without detectable myeloma protein in the serum or urine. The bone marrow contained sheets of plasma cells exhibiting pleomorphic nuclei with cleaved, multilobated, and monocytoid features that were negative for myeloperoxidase and dual esterase. Flow cytometric analysis revealed CD38hlgh/CD45low cells expressing cytoplasmic kappa light chain, without evidence of myeloid or lymphoid differentiation. Following chemotherapy, the patient developed secondary plasma cell leukemia. A high plasma cell labeling index was obtained from bone marrow and peripheral blood, indicating a poor prognosis. In addition to quantitative immunoglobulins, serum protein electrophoresis, and immunofixation electrophoresis of serum and urine, we recommend cytochemical and flow cytometric studies for evaluation of suspected plasma cell myeloma with atypical cellular features. Keywords: multiple myeloma, plasma cell, cleaved, mutilobated, monocytoid, non-secretory Introduction 11% of all myeloma cases. The other groups individually account for <10% of the remaining cases, Plasma cell myeloma constitutes approximately 1 % of with the plasmablastic type being a high-grade all malignancies and 10% of all hematologic malig malignancy (2% of all cases) associated with a poor nancies. -
Immunoglobulin M Memory B Cell Decrease in Inflammatory Bowel Disease
European Review for Medical and Pharmacological Sciences 2004; 8: 199-203 Immunoglobulin M memory B cell decrease in inflammatory bowel disease A. DI SABATINO, R. CARSETTI**, M.M. ROSADO**, R. CICCOCIOPPO, P. CAZZOLA, R. MORERA, F.P. TINOZZI*, S. TINOZZI*, G.R. CORAZZA Gastroenterology Unit and *Department of Surgery, IRCCS Policlinico S. Matteo, University of Pavia – Pavia (Italy) **Research Center Ospedale Bambino Gesù – Rome (Italy) Abstract. – Background & Objectives: Abbreviation list Memory B cells represent 30-60% of the B cell pool and can be subdivided in IgM memory and CAI = Clinical activity index switched memory. IgM memory B cells differ from CDAI = Crohn’s disease activity index switched because they express IgM and their fre- quency may vary from 20-50% of the total memo- Ig = Immunoglobulin ry pool. Switched memory express IgG, IgA or IgE and lack surface expression of IgM and IgD. Switched memory B cells derive from the germi- nal centres, whereas IgM memory B cells, which require the spleen for their survival and/or gener- Introduction ation, are involved in the immune response to en- capsulated bacteria. Since infections are one of the most frequent comorbid conditions in inflam- Several studies have focused on the mecha- matory bowel disease, we aimed to verify whether nisms that regulate T cell survival, differenti- IgM memory B cell pool was decreased in ation and activation in inflammatory bowel Crohn’s disease and ulcerative colitis patients. disease1,2, but very little is known about B Patients & Methods: Peripheral blood sam- ples were obtained from 22 Crohn’s disease pa- cells and their function. -
Solitary Plasmacytoma: a Review of Diagnosis and Management
Current Hematologic Malignancy Reports (2019) 14:63–69 https://doi.org/10.1007/s11899-019-00499-8 MULTIPLE MYELOMA (P KAPOOR, SECTION EDITOR) Solitary Plasmacytoma: a Review of Diagnosis and Management Andrew Pham1 & Anuj Mahindra1 Published online: 20 February 2019 # Springer Science+Business Media, LLC, part of Springer Nature 2019 Abstract Purpose of Review Solitary plasmacytoma is a rare plasma cell dyscrasia, classified as solitary bone plasmacytoma or solitary extramedullary plasmacytoma. These entities are diagnosed by demonstrating infiltration of a monoclonal plasma cell population in a single bone lesion or presence of plasma cells involving a soft tissue mass, respectively. Both diseases represent a single localized process without significant plasma cell infiltration into the bone marrow or evidence of end organ damage. Clinically, it is important to classify plasmacytoma as having completely undetectable bone marrow involvement versus minimal marrow involvement. Here, we discuss the diagnosis, management, and prognosis of solitary plasmacytoma. Recent Findings There have been numerous therapeutic advances in the treatment of multiple myeloma over the last few years. While the treatment paradigm for solitary plasmacytoma has not changed significantly over the years, progress has been made with regard to diagnostic tools available that can risk stratify disease, offer prognostic value, and discern solitary plasmacytoma from quiescent or asymptomatic myeloma at the time of diagnosis. Summary Despite various studies investigating the use of systemic therapy or combined modality therapy for the treatment of plasmacytoma, radiation therapy remains the mainstay of therapy. Much of the recent advancement in the management of solitary plasmacytoma has been through the development of improved diagnostic techniques. -
Selective Igm Immunodeficiency: Retrospective Analysis of 36 Adult Patients with Review of the Literature Marc F
Review Selective IgM immunodeficiency: retrospective analysis of 36 adult patients with review of the literature Marc F. Goldstein, MD*; Alex L. Goldstein, BS†; Eliot H. Dunsky, MD*; Donald J. Dvorin, MD*; George A. Belecanech, MD*; and Kfir Shamir, MD‡ Objective: To review and compare previously reported cases of selective IgM immunodeficiency (SIgMID) with the largest adult cohort obtained from a retrospective analysis of an allergy and immunology practice. Data Sources: Publications were selected from the English-only PubMed database (1966–2005) using the following keywords: IgM immunodeficiency alone and in combination with celiac disease, autoimmune disease, malignancy, and infection. Bibliographic references of relevant articles were used. Study Selection: Reported adult SIgMID cases were reviewed and included in a comparative database against our cohort. Results: Previously described patients with SIgMID include 155 adults and 157 patients of unspecified age. Thirty-six adult patients were identified with SIgMID from a database of 13,700 active adult patients (0.26%, 1:385). The mean Ϯ SD serum IgM level was 29.74 Ϯ 8.68 mg/dL (1 SD). The mean Ϯ SD age at the time of diagnosis of SIgMID was 55 Ϯ 13.5 years. Frequency of presenting symptoms included the following: recurrent upper respiratory tract infections, 77%; asthma, 47%; allergic rhinitis, 36%; vasomotor rhinitis, 19%; angioedema, 14%; and anaphylaxis, 11%. Serologically, 13% of patients had positive antinuclear antibodies (ANAs), 5% had serologic evidence of celiac disease, and nearly all had non-AB blood type. Patients also had low levels of IgM isohemagglutinins. No patients developed lymphoproliferative disease or panhypogammaglobulinemia, and none died of life-threat- ening infections, malignancy, or fulminant autoimmune-mediated diseases during a mean follow-up period of 3.7 years. -
Laboratory Testing Requirements for Diagnosis and Follow-Up of Multiple Myeloma and Related Plasma Cell Dyscrasias
Clin Chem Lab Med 2016; 54(6): 907–919 Review Maria A.V. Willrich* and Jerry A. Katzmann Laboratory testing requirements for diagnosis and follow-up of multiple myeloma and related plasma cell dyscrasias DOI 10.1515/cclm-2015-0580 Received June 19, 2015; accepted September 15, 2015; previously Monoclonal gammopathies published online October 28, 2015 overview and categorization Abstract: Monoclonal immunoglobulins are markers of Immunoglobulins are produced by plasma cells, and plasma cell proliferative diseases and have been described clonal plasma cell proliferative diseases usually secrete as the first (and perhaps best) serological tumor marker. a monoclonal immunoglobulin (M-protein) that can The unique structure of each monoclonal protein makes be used as a serologic “tumor” marker. Because of this them highly specific for each plasma cell clone. The dif- secreted monoclonal immunoglobulin, these diseases are ficulties of using monoclonal proteins for diagnosing and also called monoclonal gammopathies. The secreted pro- monitoring multiple myeloma, however, stem from the teins can be used as a diagnostic tool for the identifica- diverse disease presentations and broad range of serum tion of the clone of plasma cells as well as a quantitative protein concentrations and molecular weights. Because of marker to follow the course of the disease and response to these challenges, no single test can confidently diagnose therapy. Unlike most serologic tumor markers, M-proteins or monitor all patients. Panels of tests have been recom- are extremely diverse. The M-proteins each have unique mended for sensitivity and efficiency. In this review we variable region sequences and the molecules may range discuss the various disease presentations and the use of from pentameric IgM (~900,000 Daltons) to monomeric various tests such as protein electrophoresis and immuno- free light chains (~24,000 Daltons). -
Structure, Function, and Therapeutic Use of Igm Antibodies
antibodies Review Structure, Function, and Therapeutic Use of IgM Antibodies Bruce A. Keyt *, Ramesh Baliga, Angus M. Sinclair, Stephen F. Carroll and Marvin S. Peterson IGM Biosciences Inc, 325 East Middlefield Road, Mountain View, CA 94043, USA; [email protected] (R.B.); [email protected] (A.M.S.); [email protected] (S.F.C.); [email protected] (M.S.P.) * Correspondence: [email protected]; Tel.: +1-650-265-6458 Received: 16 September 2020; Accepted: 9 October 2020; Published: 13 October 2020 Abstract: Natural immunoglobulin M (IgM) antibodies are pentameric or hexameric macro- immunoglobulins and have been highly conserved during evolution. IgMs are initially expressed during B cell ontogeny and are the first antibodies secreted following exposure to foreign antigens. The IgM multimer has either 10 (pentamer) or 12 (hexamer) antigen binding domains consisting of paired µ heavy chains with four constant domains, each with a single variable domain, paired with a corresponding light chain. Although the antigen binding affinities of natural IgM antibodies are typically lower than IgG, their polyvalency allows for high avidity binding and efficient engagement of complement to induce complement-dependent cell lysis. The high avidity of IgM antibodies renders them particularly efficient at binding antigens present at low levels, and non-protein antigens, for example, carbohydrates or lipids present on microbial surfaces. Pentameric IgM antibodies also contain a joining (J) chain that stabilizes the pentameric structure and enables binding to several receptors. One such receptor, the polymeric immunoglobulin receptor (pIgR), is responsible for transcytosis from the vasculature to the mucosal surfaces of the lung and gastrointestinal tract. -
Selective Igm Deficiency—An Underestimated Primary Immunodeficiency
UC Irvine UC Irvine Previously Published Works Title Selective IgM Deficiency-An Underestimated Primary Immunodeficiency. Permalink https://escholarship.org/uc/item/6wg240n5 Journal Frontiers in immunology, 8(SEP) ISSN 1664-3224 Authors Gupta, Sudhir Gupta, Ankmalika Publication Date 2017 DOI 10.3389/fimmu.2017.01056 License https://creativecommons.org/licenses/by/4.0/ 4.0 Peer reviewed eScholarship.org Powered by the California Digital Library University of California REVIEW published: 05 September 2017 doi: 10.3389/fimmu.2017.01056 Selective IgM Deficiency—An Underestimated Primary Immunodeficiency Sudhir Gupta* and Ankmalika Gupta† Program in Primary Immunodeficiency and Aging, Division of Basic and Clinical Immunology, University of California at Irvine, Irvine, CA, United States Although selective IgM deficiency (SIGMD) was described almost five decades ago, it was largely ignored as a primary immunodeficiency. SIGMD is defined as serum IgM levels below two SD of mean with normal serum IgG and IgA. It appears to be more common than originally realized. SIGMD is observed in both children and adults. Patients with SIGMD may be asymptomatic; however, approximately 80% of patients with SIGMD present with infections with bacteria, viruses, fungi, and protozoa. There is an increased frequency of allergic and autoimmune diseases in SIGMD. A number Edited by: of B cell subset abnormalities have been reported and impaired specific antibodies Guzide Aksu, to Streptococcus pneumoniae responses are observed in more than 45% of cases. Ege University, Turkey Innate immunity, T cells, T cell subsets, and T cell functions are essentially normal. Reviewed by: Amos Etzioni, The pathogenesis of SIGMD remains unclear. Mice selectively deficient in secreted IgM University of Haifa, Israel are also unable to control infections from bacterial, viral, and fungal pathogens, and Isabelle Meyts, develop autoimmunity. -
Understanding MGUS and Smoldering Multiple Myeloma
Multiple Myeloma | Cancer of the Bone Marrow Understanding MGUS and Smoldering Multiple Myeloma 12650 Riverside Drive, Suite 206 North Hollywood, CA 91607 USA Telephone: 800.452.CURE (USA & Canada) 818.487.7455 (worldwide) Fax: 818.487.7454 [email protected] myeloma.org u-mgus+smm_en_2018_j4 International© 2018, Myeloma Foundation. All rights reserved. A publication of the International Myeloma Foundation Table of contents What you will learn from this booklet 4 Founded in 1990, the International Myeloma Foundation (IMF) is the first and largest organization focusing specifically on multiple myeloma. The IMF’s reach extends to more than 525,000 members in 140 countries Monoclonal gammopathy of undetermined significance 5 worldwide. The IMF is dedicated to improving the quality of life of myeloma patients while working toward prevention and a cure through our four founding principles: Research, Education, Support, and Advocacy. Smoldering multiple myeloma 10 RESEARCH The signature project of the IMF’s Research division is the Black Swan Research Initiative®, a groundbreaking and collaborative effort to develop the In closing 14 first definitive cure for myeloma. Each year, the IMF also awards Brian D. Novis Grants, which promote research for better myeloma treatments, management, and practices in the field. In addition, more than 200 leading myeloma researchers comprise Terms and definitions 14 the IMF’s International Myeloma Working Group (IMWG), a research body that has developed myeloma guidelines that are followed around the world. Finally, the IMF’s Nurse Leadership Board (NLB), comprised of nurses from leading myeloma treatment centers, develops recommendations for the nursing care of myeloma patients. EDUCATION The IMF Patient & Family Seminars and Regional Community Workshops are held around the world to provide up-to-date information presented by leading myeloma specialists and researchers directly to patients and their families. -
Immunoglobulin M 1E01-20 30-3962/R3
IMMUNOGLOBULIN M 1E01-20 30-3962/R3 IMMUNOGLOBULIN M This package insert contains information to run the Immunoglobulin M assay on the ARCHITECT c Systems and the AEROSET System. NOTE: Changes Highlighted NOTE: This package insert must be read carefully prior to product use. Package insert instructions must be followed accordingly. Reliability of assay results cannot be guaranteed if there are any deviations from the instructions in this package insert. Customer Support United States: 1-877-4ABBOTT Canada: 1-800-387-8378 (English speaking customers) 1-800-465-2675 (French speaking customers) International: Call your local Abbott representative Symbols in Product Labeling Calibrators 1 through 5 Catalog number/List number Concentration Serial number Authorized Representative in the Consult instructions for use European Community Ingredients Manufacturer In vitro diagnostic medical device Temperature limitation Batch code/Lot number Use by/Expiration date Reagent 1 Reagent 2 December 2009 ©2004, 2009 Abbott Laboratories 1 NAME REAGENT HANDLING AND STORAGE (Continued) IMMUNOGLOBULIN M Reagent Storage Unopened reagents are stable until the expiration date when stored INTENDED USE at 2 to 8°C. The Immunoglobulin M (IgM) assay is used for the quantitation of IgM in Reagent onboard stability is approximately 57 days if quality control human serum or plasma. results meet acceptance criteria. If quality control results do not meet acceptance criteria, refer to the QUALITY CONTROL section of this SUMMARY AND EXPLANATION OF TEST package insert. IgM, primarily present as a pentamer, is the first immunoglobulin class produced during an initial immune response and antigen-IgM complexes WARNINGS AND PRECAUTIONS actively fix complement.