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Haematologica Jun 2023Monoclonal gammopathy (MG) is a frequently detected clonal B-cell or plasma-cell disorder. Importantly, every multiple myeloma (MM) case is preceded by MG. Although... (Review)
Review
Monoclonal gammopathy (MG) is a frequently detected clonal B-cell or plasma-cell disorder. Importantly, every multiple myeloma (MM) case is preceded by MG. Although clinical algorithms now allow earlier treatment of patients with biomarkers of malignancy before MM-induced tissue damage (CRAB) occurs, most patients are still diagnosed late. It is important to revisit how MG should be managed in clinical practice and whether screening is required. As the prevalence of MG and other medical co-morbidities both rise with increasing age, the degree of contribution of MG to disease states other than malignant progression is often unclear. This can lead to monitoring lapses and under recognition of the organ dysfunction that can occur with monoclonal gammopathy of clinical significance (MGCS). Therefore, models of progression to MM and/or MGCS require further refinement. While MG is currently detected incidentally, a case for screening has been made with ongoing studies in this area. Screening has the potential benefit of earlier detection and prevention of both MGCS and delayed MM presentations, but important drawbacks include the psychosocial impact on individuals and resource burden on healthcare services. MG terminology should transition alongside our increasing understanding of the condition and genomic characterization that have already begun to revise the MG nomenclature. The biology of MG has been poorly understood and is often inferred from the biology of MM, which is unhelpful. We review the literature and case for MG screening in this paper. In particular, we highlight areas that require focus to establish screening for MG.
Topics: Humans; Paraproteinemias; Monoclonal Gammopathy of Undetermined Significance; Multiple Myeloma; B-Lymphocytes; Disease Progression
PubMed: 36373250
DOI: 10.3324/haematol.2022.281802 -
Frontiers in Immunology 2022Multiple myeloma (MM) is the third most common malignant neoplasm of the hematological system. It often develops from monoclonal gammopathy of undetermined significance... (Review)
Review
Multiple myeloma (MM) is the third most common malignant neoplasm of the hematological system. It often develops from monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) precursor states. In this process, the immune microenvironment interacts with the MM cells to exert yin and yang effects, promoting tumor progression on the one hand and inhibiting it on the other. Despite significant therapeutic advances, MM remains incurable, and the main reason for this may be related to the complex and variable immune microenvironment. Therefore, it is crucial to investigate the dynamic relationship between the immune microenvironment and tumors, to elucidate the molecular mechanisms of different factors in the microenvironment, and to develop novel therapeutic agents targeting the immune microenvironment of MM. In this paper, we review the latest research progress and describe the dual influences of the immune microenvironment on the development and progression of MM from the perspective of immune cells and molecules.
Topics: Humans; Monoclonal Gammopathy of Undetermined Significance; Multiple Myeloma; Smoldering Multiple Myeloma; Tumor Microenvironment; Yin-Yang
PubMed: 35958625
DOI: 10.3389/fimmu.2022.925266 -
Revista Medica de Chile May 2021Monoclonal gammopathies of uncertain significance (MGUS) correspond to pre-malignant hematological disorders characterized by the production of a monoclonal protein and...
Monoclonal gammopathies of uncertain significance (MGUS) correspond to pre-malignant hematological disorders characterized by the production of a monoclonal protein and infiltration of less than 10% of the bone marrow by plasma cells. Its importance lies in the risk of progression to malignant disorders and in the association with different renal, neurological and skin manifestations. There are pathophysiological mechanisms that support a causal relationship between monoclonal gammopathies (MGs) and different skin diseases, such as type I cryoglobulinemia (CG), primary systemic amyloidosis (PSA) or necrobiotic xanthogranuloma (NXG). However, there is a group of skin diseases associated with MGs whose pathogenesis has not been elucidated. In this context, the role of the dermatologist is crucial in the suspicion of different haematological disorders based on skin manifestations and in the multidisciplinary treatment of these patients. In this article, we carry out an exhaustive review of the literature published in this area and propose a screening algorithm for MGs in patients with specific skin diseases.
Topics: Bone Marrow; Humans; Immunoglobulin Light-chain Amyloidosis; Monoclonal Gammopathy of Undetermined Significance; Paraproteinemias; Skin Diseases
PubMed: 34751328
DOI: 10.4067/s0034-98872021000500747 -
Haematologica Jun 2023
Topics: Humans; Paraproteinemias; Monoclonal Gammopathy of Undetermined Significance
PubMed: 36453107
DOI: 10.3324/haematol.2022.282271 -
Medicine Jun 2016To review the reported evidence on the therapeutic management of IgG4-related disease (IgG4-RD) in clinical practice.A systematic search of the literature was conducted.... (Review)
Review
To review the reported evidence on the therapeutic management of IgG4-related disease (IgG4-RD) in clinical practice.A systematic search of the literature was conducted. The primary outcome measured was the rate of efficacy of first-line therapeutic approaches. Secondary outcomes measured included the rate of disease relapse, the outcome of untreated patients, the rate of patients without drug therapy at the end of follow-up, the rate of side effects, and mortality. The MOOSE, AHRQ, STROBE, and GRACE recommendations/statements were followed.The results of the systematic search strategy yielded 62 studies that included a total of 3034 patients. Complete information about first-line therapeutic regimens was detailed in 1952 patients, including glucocorticoid-based regimens in 1437 (74%), drug-free regimens in 213 (11%), and other therapies in 38 (2%). No therapy (wait and see management) was reported in 264 (13%) patients. The efficacy of monotherapy with glucocorticoids was specified in 1220 patients, of whom 97% had a therapeutic response. Relapses, however, were reported in 464/1395 (33%) patients despite typically short follow-up periods. Therapeutic efficacy was reported in 219/231 (95%) of relapses treated with glucocorticoids, 56/69 (81%) of those treated with azathioprine, 16/22 (72%) of those treated with other immunosuppressive agents, and in the 9 cases treated with rituximab (100%). In 14 studies, the authors detailed the outcome of 159/246 patients with wait-and-see management; spontaneous improvement or resolution was reported in 68 (43%) cases. Wide heterogeneity was observed with respect to the first-line therapeutic approaches used for the different organ-specific disease subsets, including significant differences in the mean dose of glucocorticoids used.Nearly 70% of reported IgG4-RD patients are treated with oral glucocorticoids in monotherapy. However, the therapeutic management is heavily influenced by geographical, epidemiological, and clinical factors, especially with respect to the predominant organ affected. The frequency of glucocorticoid failure to induce sustained remissions both during and after treatment and the assessment of glucocorticoid toxicity in IgG4-RD require further study.
Topics: Humans; Immunoglobulin G; Paraproteinemias
PubMed: 27368010
DOI: 10.1097/MD.0000000000004002 -
Indian Journal of Dermatology,... 2023
Topics: Humans; Pancytopenia; Paraproteinemias
PubMed: 35146977
DOI: 10.25259/IJDVL_425_2021 -
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 -
Clinical and Experimental Rheumatology Sep 2023
Topics: Humans; Lupus Nephritis; Paraproteinemias
PubMed: 37199177
DOI: 10.55563/clinexprheumatol/mqfpi4 -
Frontiers in Immunology 2023The adaptive immune system of jawed vertebrates generates a highly diverse repertoire of antibodies to meet the antigenic challenges of a constantly evolving biological... (Review)
Review
The adaptive immune system of jawed vertebrates generates a highly diverse repertoire of antibodies to meet the antigenic challenges of a constantly evolving biological ecosystem. Most of the diversity is generated by two mechanisms: V(D)J gene recombination and somatic hypermutation (SHM). SHM introduces changes in the variable domain of antibodies, mostly in the regions that form the paratope, yielding antibodies with higher antigen binding affinity. However, antigen recognition is only possible if the antibody folds into a stable functional conformation. Therefore, a key force determining the survival of B cell clones undergoing somatic hypermutation is the ability of the mutated heavy and light chains to efficiently fold and assemble into a functional antibody. The antibody is the structural context where the selection of the somatic mutations occurs, and where both the heavy and light chains benefit from protective mechanisms that counteract the potentially deleterious impact of the changes. However, in patients with monoclonal gammopathies, the proliferating plasma cell clone may overproduce the light chain, which is then secreted into the bloodstream. This places the light chain out of the protective context provided by the quaternary structure of the antibody, increasing the risk of misfolding and aggregation due to destabilizing somatic mutations. Light chain-derived (AL) amyloidosis, light chain deposition disease (LCDD), Fanconi syndrome, and myeloma (cast) nephropathy are a diverse group of diseases derived from the pathologic aggregation of light chains, in which somatic mutations are recognized to play a role. In this review, we address the mechanisms by which somatic mutations promote the misfolding and pathological aggregation of the light chains, with an emphasis on AL amyloidosis. We also analyze the contribution of the variable domain (V) gene segments and somatic mutations on light chain cytotoxicity, organ tropism, and structure of the AL fibrils. Finally, we analyze the most recent advances in the development of computational algorithms to predict the role of somatic mutations in the cardiotoxicity of amyloidogenic light chains and discuss the challenges and perspectives that this approach faces.
Topics: Animals; Humans; Multiple Myeloma; Friends; Ecosystem; B-Lymphocytes; Paraproteinemias
PubMed: 37520549
DOI: 10.3389/fimmu.2023.1203425 -
Acta Medica Portuguesa May 2021Monoclonal gammopathy of renal significance (MGRS) is described as a hematologic condition characterized by nephrotoxicmonoclonal proteins produced by a non-malignant... (Review)
Review
INTRODUCTION
Monoclonal gammopathy of renal significance (MGRS) is described as a hematologic condition characterized by nephrotoxicmonoclonal proteins produced by a non-malignant B-cell or plasma cell clone. Nevertheless, MGRS can cause serious renal lesions, leading to high morbidity. In C3 glomerulonephritis, a monoclonal protein can cause renal damage indirectly. Acting as an autoantibody, the protein cannot be detected in the kidney biopsy, promoting the dysregulation of the alternative pathway of the complement system.
MATERIAL AND METHODS
This non-systematic review was based on a comprehensive search in databases and scientific journals, such as PubMed, Nature Reviews Nephrology and Kidney International, including the terms 'C3 Glomerulonephritis' and 'Monoclonal gammopathy of renal significance'. We review the pathophysiology, presentation, diagnosis, differential diagnosis and treatment of C3 glomerulonephritis associated with MGRS.
DISCUSSION
With the increasing understanding of the complex interaction between monoclonal gammopathy and renal damage, such as C3 glomerulonephritis, it becomes clear that an early recognition is crucial, as Ig-directed therapy might improve outcomes. In this context, and in order to maximize the chance of a correct diagnosis, renal biopsy is mandatory to determine the exact nature of the lesion, and the severity of renal disease. Conclusion: It is important to make an early diagnosis of MGRS-associated C3 glomerulonephritis in order to prevent not only the progression to a hematological malignancy, but also end-stage renal disease.
Topics: Autoantibodies; Glomerulonephritis; Humans; Hypergammaglobulinemia; Kidney; Kidney Diseases; Monoclonal Gammopathy of Undetermined Significance; Paraproteinemias
PubMed: 33819437
DOI: 10.20344/amp.13823