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Haematologica Jun 2023
Topics: Humans; Paraproteinemias; Monoclonal Gammopathy of Undetermined Significance
PubMed: 36453107
DOI: 10.3324/haematol.2022.282271 -
Blood Cells, Molecules & Diseases Sep 2016
Topics: Aged; Anemia, Hemolytic, Autoimmune; Bone Marrow Cells; Female; Humans; Paraproteinemias
PubMed: 27519938
DOI: 10.1016/j.bcmd.2016.06.003 -
Annals of Clinical and Laboratory... Sep 2019Monoclonal gammopathy of renal significance (MGRS) is a state of circulating monoclonal immunoglobulin (Ig) and light chains that cause kidney injury without definite... (Review)
Review
Monoclonal gammopathy of renal significance (MGRS) is a state of circulating monoclonal immunoglobulin (Ig) and light chains that cause kidney injury without definite evidence of multiple myeloma (MM). Although chemotherapy is used to treat many variants of MGRS and has been recently recommended, relatively limited clinical validation studies are available. A few transgenic models of MM reveal renal deposition of monoclonal Ig and light chains. We have demonstrated that the XBP1s-transgenic mouse model from early plasma cell dyscrasia to MM reveals monoclonal IgG/kappa deposition at the subendothelial spaces of the glomeruli, mimicking proliferative glomerulonephritis with monoclonal immunoglobulin deposits. Inhibition of a key immune-modulator, gp96/grp94, genetically or pharmacologically results in a significant reduction of plasma cells within the bone marrow and reduced renal deposition of monoclonal IgG and kappa light chain. This article will review the emerging role of and animal models from plasma cell dyscrasia to MM in understanding the renal deposition of monoclonal Ig and light chains, along with its potential treatment strategies.
Topics: Animals; Creatinine; Disease Models, Animal; Humans; Immunoglobulin Light Chains; Kidney Tubules; Paraproteinemias
PubMed: 31471332
DOI: No ID Found -
Cardiology Clinics Nov 2019Light chain amyloidosis is a deadly disease in which a monoclonal plasma cell dyscrasia produces misfolded immunoglobulin light chains (AL) that aggregate and form rigid... (Review)
Review
Light chain amyloidosis is a deadly disease in which a monoclonal plasma cell dyscrasia produces misfolded immunoglobulin light chains (AL) that aggregate and form rigid amyloid fibrils. The amyloid deposits infiltrate one or more organs, leading to injury and severe dysfunction. The degree of cardiac involvement is a major driver of morbidity and mortality. Early diagnosis and treatment are crucial to prevent irreversible end-organ damage and improve overall survival. Treatment of AL cardiac amyloidosis involves eliminating the underlying plasma cell dyscrasia with chemotherapy and pursuing supportive heart failure management.
Topics: Amyloidosis; Cardiomyopathies; Disease Management; Early Diagnosis; Humans; Paraproteinemias
PubMed: 31587789
DOI: 10.1016/j.ccl.2019.07.013 -
Continuum (Minneapolis, Minn.) Jun 2017This article reviews the spectrum of neurologic complications associated with lymphoma, leukemia, and paraproteinemic disorders. While leptomeningeal metastasis is the... (Review)
Review
PURPOSE OF REVIEW
This article reviews the spectrum of neurologic complications associated with lymphoma, leukemia, and paraproteinemic disorders. While leptomeningeal metastasis is the most common complication of lymphoma and leukemia and peripheral neuropathy is the most common complication of paraproteinemic disorders, clinicians need to be familiar with the diverse neurologic complications of these disorders.
RECENT FINDINGS
Lymphomatous nervous system involvement can be difficult to diagnose, especially when it is the presenting symptom. CSF cytology and flow cytometry, as well as the imaging pattern, assist in diagnosis. Neurologic complications are less common in Hodgkin lymphoma; however, some unique paraneoplastic syndromes are associated with Hodgkin lymphoma, including primary central nervous system angiitis, limbic encephalitis, and cerebellar degeneration. Recent reports suggest that anti-metabotropic glutamate receptor 5 (mGluR5) antibodies are associated with limbic encephalitis and that anti-Tr antibodies are associated with cerebellar degeneration in Hodgkin lymphoma. Polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma cell disorder, and skin changes (POEMS) syndrome is often misdiagnosed as chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). A lambda protein, thrombocytosis, and elevated vascular endothelial growth factor (VEGF) can all be helpful clues in diagnosis. Early recognition is important, as the neuropathy responds to radiation therapy or chemotherapy.
SUMMARY
Neurologic involvement can occur throughout the disease course in lymphoma and leukemia, including at presentation, with systemic progression, and at relapse. In paraproteinemias, the peripheral neuropathy phenotype, monoclonal protein type, and associated autonomic and systemic features aid in identification of an underlying plasma cell disorder.
Topics: Diagnosis, Differential; Female; Humans; Leukemia; Lymphoma; Lymphoma, Large B-Cell, Diffuse; Middle Aged; Nervous System Diseases; Paraproteinemias
PubMed: 28570324
DOI: 10.1212/CON.0000000000000468 -
Indian Journal of Dermatology,... 2023
Topics: Humans; Pancytopenia; Paraproteinemias
PubMed: 35146977
DOI: 10.25259/IJDVL_425_2021 -
Annals of Clinical and Laboratory... 2016
Topics: Aged, 80 and over; Humans; Iron; Magnetic Resonance Imaging; Male; Paraproteinemias
PubMed: 27098634
DOI: No ID Found -
Clinical Chemistry Mar 2020Monoclonal gammopathies (MGs) are plasma cell disorders defined by the clonal expansion of plasma cells, resulting in the characteristic excretion of a monoclonal... (Review)
Review
BACKGROUND
Monoclonal gammopathies (MGs) are plasma cell disorders defined by the clonal expansion of plasma cells, resulting in the characteristic excretion of a monoclonal immunoglobulin (M-protein). M-protein detection and quantification are integral parts of the diagnosis and monitoring of MGs. Novel treatment modalities impose new challenges on the traditional electrophoretic and immunochemical methods that are routinely used for M-protein diagnostics, such as interferences from therapeutic monoclonal antibodies and the need for increased analytical sensitivity to measure minimal residual disease.
CONTENT
Mass spectrometry (MS) is ideally suited to accurate mass measurements or targeted measurement of unique clonotypic peptide fragments. Based on these features, MS-based methods allow for the analytically sensitive measurement of the patient-specific M-protein.
SUMMARY
This review provides a comprehensive overview of the MS methods that have been developed recently to detect, characterize, and quantify M-proteins. The advantages and disadvantages of using these techniques in clinical practice and the impact they will have on the management of patients with MGs are discussed.
Topics: Antibodies, Monoclonal; Biomarkers; Chromatography, High Pressure Liquid; Humans; Immunoglobulin Light Chains; Mass Spectrometry; Paraproteinemias; Peptides
PubMed: 32031591
DOI: 10.1093/clinchem/hvz041 -
Clinical Journal of the American... Dec 2018
Topics: Disease Progression; Humans; Kidney Diseases; Monoclonal Gammopathy of Undetermined Significance; Paraproteinemias; Veterans
PubMed: 30442863
DOI: 10.2215/CJN.12401018 -
Haematologica Dec 2023Monoclonal gammopathy of undetermined significance (MGUS) is an asymptomatic precursor condition that precedes multiple myeloma and related disorders but has also been...
Disease associations with monoclonal gammopathy of undetermined significance can only be evaluated using screened cohorts: results from the population-based iStopMM study.
Monoclonal gammopathy of undetermined significance (MGUS) is an asymptomatic precursor condition that precedes multiple myeloma and related disorders but has also been associated with other medical conditions. Since systematic screening is not recommended, MGUS is typically diagnosed due to underlying diseases and most cases are not diagnosed. Most previous studies on MGUS disease associations have been based on clinical cohorts, possibly resulting in selection bias. Here we estimate this selection bias by comparing clinically diagnosed and screened individuals with MGUS with regards to demographics, laboratory features, and comorbidities. A total of 75,422 participants in the Iceland Screens, Treats, or Prevents Multiple Myeloma (iStopMM) study were screened for MGUS by serum protein electrophoresis, immunofixation and free light chain assay (clinicaltrials gov. Identifier: NCT03327597). We identified 3,352 individuals with MGUS, whereof 240 had previously been clinically diagnosed (clinical MGUS), and crosslinked our data with large, nationwide registries for information on comorbidities. Those with clinical MGUS were more likely to have at least one comorbidity (odds ratio=2.24; 95% confidence interval: 1.30-4.19), and on average had more comorbidities than the screened MGUS group (3.23 vs. 2.36, mean difference 0.68; 95% confidence interval: 0.46-0.90). They were also more likely to have rheumatological disease, neurological disease, chronic kidney disease, liver disease, heart failure, or endocrine disorders. These findings indicate that individuals with clinical MGUS have more comorbidities than the general MGUS population and that previous studies have been affected by significant selection bias. Our findings highlight the importance of screening data when studying biological and epidemiological implications of MGUS.
Topics: Humans; Multiple Myeloma; Monoclonal Gammopathy of Undetermined Significance; Iceland; Paraproteinemias; Comorbidity; Disease Progression
PubMed: 37439374
DOI: 10.3324/haematol.2023.283191