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Blood Oct 2018Monoclonal gammopathy is a common condition, particularly in the elderly. It can indicate symptomatic multiple myeloma or another overt malignant lymphoid disorder... (Review)
Review
Monoclonal gammopathy is a common condition, particularly in the elderly. It can indicate symptomatic multiple myeloma or another overt malignant lymphoid disorder requiring immediate chemotherapy. More frequently, it results from a small and/or quiescent secreting B-cell clone, is completely asymptomatic, and requires regular monitoring only, defining a monoclonal gammopathy of unknown significance (MGUS). Sometimes, although quiescent and not requiring any treatment per se, the clone is associated with potentially severe organ damage due to the toxicity of the monoclonal immunoglobulin or to other mechanisms. The latter situation is increasingly observed but still poorly recognized and frequently undertreated, although it often requires rapid specific intervention to preserve involved organ function. To improve early recognition and management of these small B-cell clone-related disorders, we propose to introduce the concept of monoclonal gammopathy of clinical significance (MGCS). This report identifies the spectrum of MGCSs that are classified according to mechanisms of tissue injury. It highlights the diversity of these disorders for which diagnosis and treatment are often challenging in clinical practice and require a multidisciplinary approach. Principles of management, including main diagnostic and therapeutic procedures, are also described. Importantly, efficient control of the underlying B-cell clone usually results in organ improvement. Currently, it relies mainly on chemotherapy and other anti-B-cell/plasma cell agents, which should aim at rapidly producing the best hematological response.
Topics: Animals; Autoantibodies; B-Lymphocytes; Cytokines; Humans; Immunoglobulins; Paraproteinemias
PubMed: 30012636
DOI: 10.1182/blood-2018-04-839480 -
Ugeskrift For Laeger Oct 2021Monoclonal gammopathies range from benign conditions to severe malignancies. A summary is given in this review. Overall, the prevalence is high; monoclonal gammopathies... (Review)
Review
Monoclonal gammopathies range from benign conditions to severe malignancies. A summary is given in this review. Overall, the prevalence is high; monoclonal gammopathies (MGUS) occur in > 3% of persons above 50 years of age. Approximately 400 new cases of multiple myeloma and 80 new cases of amyloid light-chain (AL) amyloidosis are diagnosed yearly in Denmark. MGUS is most often asymptomatic, but M-protein associated syndromes exist and should be considered when finding M-protein. Serum free light kappa and lambda chain analysis, CT, PET/CT and whole-body MRI have revolutionised diagnostics and monitoring of monoclonal gammopathies. New treatment modalities have improved outcome in multiple myeloma and AL amyloidosis.
Topics: Humans; Monoclonal Gammopathy of Undetermined Significance; Multiple Myeloma; Paraproteinemias; Positron Emission Tomography Computed Tomography
PubMed: 34709161
DOI: No ID Found -
Journal of the American Society of... Oct 2020Little is known about the rate and predictors of finding lesions of monoclonal gammopathy (MG) of renal significance (MGRS) on kidney biopsy specimens among patients...
BACKGROUND
Little is known about the rate and predictors of finding lesions of monoclonal gammopathy (MG) of renal significance (MGRS) on kidney biopsy specimens among patients with MG.
METHODS
We reviewed the medical records from 2013 to 2018 at the Mayo Clinic in Rochester, Minnesota, to identify patients with MG and whether they had undergone a kidney biopsy. In a more select group of patients with MG from 2017 to 2018, we conducted a review of records to determine how many had underlying CKD, which of those with CKD had undergone a kidney biopsy, and reasons for deferring a kidney biopsy.
RESULTS
Between 2013 and 2018, we identified 6300 patients who had MG, 160 (2.5%) of whom had undergone a kidney biopsy. Of the 160 patients, 64 (40%) had an MGRS lesion; amyloid light chain amyloidosis, the most common finding, accounted for nearly half of these lesions. In the non-MGRS group comprising 96 patients, 23 had arteriosclerosis, the most common finding. In multivariate analysis, strong predictors of finding an MGRS lesion included the presence of an elevated free light chain ratio, proteinuria, and hematuria. Among 596 patients with CKD and MG from 2017 to 2018, 62 (10.4%) underwent a kidney biopsy. Kidney biopsy was deferred for 70 patients (20%); for 62 of the 70, the diagnosis was already known, and eight were not candidates for therapy. Younger age and higher proteinuria and serum creatinine levels increased the likelihood that the patient would undergo a kidney biopsy.
CONCLUSIONS
Proteinuria ≥1.5 g/d, hematuria, and an elevated free light chain ratio increase the likelihood of finding MGRS, and a kidney biopsy should be highly considered in such patients.
Topics: Aged; Aged, 80 and over; Biopsy; Female; Humans; Kidney Diseases; Male; Middle Aged; Paraproteinemias; Patient Selection; Practice Patterns, Physicians'; Referral and Consultation; Retrospective Studies; Risk Factors
PubMed: 32747354
DOI: 10.1681/ASN.2020010054 -
Clinical Medicine (London, England) May 2023The term monoclonal gammopathies of renal significance (MGRS) encompasses a group of renal histopathological lesions fulfilling two criteria: (a) they are caused by... (Review)
Review
The term monoclonal gammopathies of renal significance (MGRS) encompasses a group of renal histopathological lesions fulfilling two criteria: (a) they are caused by nephrotoxic monoclonal immunoglobulins and (b) the monoclonal immunoglobulins are produced by small B-cell or plasma cell clones which do not meet the criteria for multiple myeloma or malignant lymphoma. Here, we provide a review of the MGRS definition and related terminology and elaborate on the diagnostic approach and treatment principles from the general physician perspective.
Topics: Humans; Kidney Diseases; Paraproteinemias; Kidney; Multiple Myeloma; Immunoglobulins
PubMed: 37236803
DOI: 10.7861/clinmed.2023-RM3 -
Clinical Chemistry and Laboratory... Jun 2016
Topics: Blood Protein Electrophoresis; Humans; Immunoassay; Immunoelectrophoresis; Immunoglobulin Light Chains; Multiple Myeloma; Myeloma Proteins; Paraproteinemias; Practice Guidelines as Topic
PubMed: 27107838
DOI: 10.1515/cclm-2016-0268 -
Blood Apr 2020The TEMPI syndrome is a rare and acquired disorder characterized by 5 salient features, which compose its name: (1) telangiectasias; (2) elevated erythropoietin and...
The TEMPI syndrome is a rare and acquired disorder characterized by 5 salient features, which compose its name: (1) telangiectasias; (2) elevated erythropoietin and erythrocytosis; (3) monoclonal gammopathy; (4) perinephric fluid collections; and (5) intrapulmonary shunting. Complete resolution of symptoms following treatment with plasma cell-directed therapy supports the hypothesis that the monoclonal antibody is causal and pathogenic. Understanding the basis of the TEMPI syndrome will depend on the identification of additional patients and a coordinated international effort.
Topics: Erythropoietin; Humans; Lung Diseases; Paraproteinemias; Polycythemia; Syndrome; Telangiectasis
PubMed: 32108223
DOI: 10.1182/blood.2019004216 -
Revista Medica de Chile Aug 2019Hematological neoplasms are tumors of cells in different states of maturation and differentiation. Since monoclonal gammopathies (MG) refer to B mature lymphocyte... (Review)
Review
Hematological neoplasms are tumors of cells in different states of maturation and differentiation. Since monoclonal gammopathies (MG) refer to B mature lymphocyte neoplasms, lymphogenesis should be well known. We must keep in mind that the last stage of maturation of these lymphocytes is the plasma cell. This is how a MG could appear in the context of a plasma cell neoplasm, such as multiple myeloma or amyloidosis, but also in relation to a lymphoma. A monoclonal peak is produced by mature B lymphocytes or plasma cells that secrete a monoclonal protein (Immunoglobulin), and represents a MG. But it must be emphasized that, in the correct clinical context, a hypogammaglobulinemia can represent a MG as well. Another important point is the understanding and interpretation of requested tests, such as protein electrophoresis (PEP), immunofixation (IFx) or serum free light chains (sFLC). The current MG screening panel includes these three studies (PEF, IFx, sFLC), although a simpler panel measuring PEF and sFLC has also been proposed, but not yet formally validated. Therefore, screening done only with PEP is insufficient.
Topics: B-Lymphocytes; Blood Protein Electrophoresis; Humans; Neoplasms, Plasma Cell; Paraproteinemias; Paraproteins
PubMed: 31859969
DOI: 10.4067/S0034-98872019000801036 -
Veterinary Clinical Pathology Dec 2022Hyperglobulinemia is reported in 26% of canine chronic B-cell lymphocytic leukemia (B-CLL) cases. However, few cases have been characterized by protein electrophoresis...
BACKGROUND
Hyperglobulinemia is reported in 26% of canine chronic B-cell lymphocytic leukemia (B-CLL) cases. However, few cases have been characterized by protein electrophoresis and immunofixation (IF), and the incidence of a monoclonal protein (M-protein) is unknown using these techniques.
OBJECTIVE
To characterize and determine the proportion of canine B-CLL cases with an M-protein using plasma protein electrophoresis (PPE), routine and free light chain (fLC) IF, and to assess if productive B-CLL cases express MUM1/IRF4 by cell tube block (CTB).
METHODS
PPE, routine (targeting IgG, IgA, IgM, IgG4, and light chain) and fLC IF were performed using 48 dog B-CLL plasma samples from patients diagnosed via peripheral blood flow cytometry. CTB was performed on a separate cohort of 15 patients.
RESULTS
Hyperproteinemia (>7.5 g/dL) was present in 17/48 cases (35%). An M-protein was detected in 32/48 cases (67%). Of these, 19/32 cases (59%) had only complete (monoclonal heavy and light chain) M-proteins detected, 10/32 cases (31%) had both complete and fLC M-proteins detected, and 3/32 cases (9%) had only an fLC M-protein detected. IgM was the most common clonal immunoglobulin isotype detected (23 cases). CD21 cell counts were higher in cases with detectable M-protein. Plasma fLC IF suggested β-γ region interference, likely caused by clotting proteins. All B-CLL cases consistently expressed PAX5 and did not express MUM1/IRF4.
CONCLUSIONS
Most B-CLL cases had an M-protein and were not hyperproteinemic. Most cases with paraproteins had a complete IgM monoclonal gammopathy; a subset had documented fLCs. The prognostic significance of heavy and fLC presence should be evaluated.
Topics: Dogs; Animals; Leukemia, Lymphocytic, Chronic, B-Cell; Immunoglobulin Light Chains; Immunoelectrophoresis; Paraproteinemias; Immunoglobulin M; Dog Diseases
PubMed: 35883213
DOI: 10.1111/vcp.13156 -
Blood Apr 2023
Topics: Humans; Monoclonal Gammopathy of Undetermined Significance; Paraproteinemias; Thrombosis
PubMed: 36626584
DOI: 10.1182/blood.2022018797 -
Clinical Journal of the American... Jan 2018Dysproteinemia is characterized by the overproduction of an Ig by clonal expansion of cells from the B cell lineage. The resultant monoclonal protein can be composed of... (Review)
Review
Dysproteinemia is characterized by the overproduction of an Ig by clonal expansion of cells from the B cell lineage. The resultant monoclonal protein can be composed of the entire Ig or its components. Monoclonal proteins are increasingly recognized as a contributor to kidney disease. They can cause injury in all areas of the kidney, including the glomerular, tubular, and vascular compartments. In the glomerulus, the major mechanism of injury is deposition. Examples of this include Ig amyloidosis, monoclonal Ig deposition disease, immunotactoid glomerulopathy, and cryoglobulinemic GN specifically from types 1 and 2 cryoglobulins. Mechanisms that do not involve Ig deposition include the activation of the complement system, which causes complement deposition in C3 glomerulopathy, and cytokines/growth factors as seen in thrombotic microangiopathy and precipitation, which is involved with cryoglobulinemia. It is important to recognize that nephrotoxic monoclonal proteins can be produced by clones from any of the B cell lineages and that a malignant state is not required for the development of kidney disease. The nephrotoxic clones that do not meet requirement for a malignant condition are now called monoclonal gammopathy of renal significance. Whether it is a malignancy or monoclonal gammopathy of renal significance, preservation of renal function requires substantial reduction of the monoclonal protein. With better understanding of the pathogenesis, clone-directed strategies, such as rituximab against CD20 expressing B cell and bortezomib against plasma cell clones, have been used in the treatment of these diseases. These clone-directed therapies been found to be more effective than immunosuppressive regimens used in nonmonoclonal protein-related kidney diseases.
Topics: Animals; Autoimmunity; B-Lymphocytes; Cell Lineage; Complement Activation; Cytotoxicity, Immunologic; Humans; Immunoglobulin G; Kidney Diseases; Kidney Glomerulus; Paraproteinemias; Prognosis; Risk Factors
PubMed: 29114004
DOI: 10.2215/CJN.00560117