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      Monoclonal Gammopathy of Undetermined Significance (MGUS)—Not So Asymptomatic after All

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          Abstract

          Monoclonal Gammopathy of Undetermined Significance (MGUS) is considered to be a benign precursor condition that may progress to a lymphoproliferative disease or multiple myeloma. Most patients do not progress to an overt condition, but nevertheless, MGUS is associated with a shortened life expectancy and, in a minority of cases, a number of co-morbid conditions that include an increased fracture risk, renal impairment, peripheral neuropathy, secondary immunodeficiency, and cardiovascular disease. This review aims to consolidate current evidence for the significance of these co-morbidities before considering how best to approach these symptoms and signs, which are often encountered in primary care or within a number of specialties in secondary care.

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          Single-cell RNA sequencing reveals compromised immune microenvironment in precursor stages of multiple myeloma

          Oksana Zavidij, Nicholas J Haradhvala, Tarek H. Mouhieddine … (2020)
          Precursor states of Multiple Myeloma (MM) and its native tumor microenvironment need in-depth molecular characterization to better stratify and treat patients at risk. Using single-cell RNA sequencing of bone marrow cells from precursor stages, MGUS and smoldering myeloma (SMM), to full-blown MM alongside healthy donors, we demonstrate early immune changes during patient progression. We find NK cell abundance is frequently increased in early stages, and associated with altered chemokine receptor expression. As early as SMM, we show loss of GrK + memory cytotoxic T-cells, and show their critical role in MM immunosurveillance in mouse models. Finally, we report MHC class II dysregulation in CD14 + monocytes, which results in T cell suppression in vitro . These results provide a comprehensive map of immune changes at play over the evolution of pre-malignant MM, which will help develop strategies for immune-based patient stratification.
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            Proliferative glomerulonephritis with monoclonal IgG deposits.

            G. Markowitz, D A Valeri, Anjali Satoskar … (2009)
            Dysproteinemias that result in monoclonal glomerular deposits of IgG are relatively uncommon. Here, we report the largest series of proliferative glomerulonephritis with monoclonal IgG deposits, a form of renal involvement by monoclonal gammopathy that mimics immune-complex glomerulonephritis. We retrospectively identified 37 patients, most of whom were white (81%), female (62%), or older than 50 yr (65%). At presentation, 49% had nephrotic syndrome, 68% had renal insufficiency, and 77% had hematuria. In 30% of the patients, we identified a monoclonal serum protein with the same heavy- and light-chain isotypes as the glomerular deposits (mostly IgG1 or IgG2), but only one patient had myeloma. Histologic patterns were predominantly membranoproliferative (57%) or endocapillary proliferative (35%) with membranous features. Electron microscopy revealed granular, nonorganized deposits, and immunofluorescence demonstrated glomerular deposits that stained for a single light-chain isotype and a single heavy-chain subtype, most commonly IgG3kappa (53%). During an average of 30.3 mo of follow-up for 32 patients with available data, 38% had complete or partial recovery, 38% had persistent renal dysfunction, and 22% progressed to ESRD. Correlates of ESRD on univariate analysis were higher creatinine at biopsy, percentage of glomerulosclerosis, and degree of interstitial fibrosis but not immunomodulatory treatment or presence of a monoclonal spike. On multivariate analysis, higher percentage of glomerulosclerosis was the only independent predictor of ESRD. Only one patient lacking a monoclonal spike at presentation subsequently developed a monoclonal spike and no patient with a monoclonal spike at presentation subsequently developed a hematologic malignancy. We conclude that proliferative glomerulonephritis with monoclonal IgG deposits does not seem to be a precursor of myeloma in the vast majority of patients.
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              How I treat monoclonal gammopathy of renal significance (MGRS).

              Jean-Paul Fermand, Frank Bridoux, Robert A Kyle … (2013)
              Recently, the term monoclonal gammopathy of renal significance (MGRS) was introduced to distinguish monoclonal gammopathies that result in the development of kidney disease from those that are benign. By definition, patients with MGRS have B-cell clones that do not meet the definition of multiple myeloma or lymphoma. Nevertheless, these clones produce monoclonal proteins that are capable of injuring the kidney resulting in permanent damage. Except for immunoglobulin light chain amyloidosis with heart involvement in which death can be rapid, treatment of MGRS is often indicated more to preserve kidney function and prevent recurrence after kidney transplantation rather than the prolongation of life. Clinical trials are rare for MGRS-related kidney diseases, except in immunoglobulin light chain amyloidosis. Treatment recommendations are therefore based on the clinical data obtained from treatment of the clonal disorder in its malignant state. The establishment of these treatment recommendations is important until data can be obtained by clinical trials of MGRS-related kidney diseases.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Cancers (Basel)
                Journal ID (iso-abbrev): Cancers (Basel)
                Journal ID (publisher-id): cancers
                Title: Cancers
                Publisher: MDPI
                ISSN (Electronic): 2072-6694
                Publication date (Electronic): 12 June 2020
                Publication date Collection: June 2020
                Volume: 12
                Issue: 6
                Electronic Location Identifier: 1554
                Affiliations
                [1 ]Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA; OliverC_Lomas@ 123456dfci.harvard.edu (O.C.L.); TarekH_Mouhieddine@ 123456DFCI.HARVARD.EDU (T.H.M.); Sabrin_tahri@ 123456dfci.harvard.edu (S.T.)
                [2 ]Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
                Author notes
                Author information
                https://orcid.org/0000-0003-4121-6468
                https://orcid.org/0000-0002-1190-5978
                Article
                Publisher ID: cancers-12-01554
                DOI: 10.3390/cancers12061554
                PMC ID: 7352603
                PubMed ID: 32545521
                SO-VID: 9ab6a2e6-0a18-47cd-8049-41f7cac523f5
                Copyright © © 2020 by the authors.
                License:

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 18 April 2020
                Date accepted : 10 June 2020
                Categories
                Subject: Review

                Keywords: mgus,multiple myeloma,paraprotein,neuropathy,fracture,mgrs,osteoporosis
                Data availability:
                Keywords: mgus, multiple myeloma, paraprotein, neuropathy, fracture, mgrs, osteoporosis

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