-
Clinica Chimica Acta; International... Jan 2014Monoclonal free light chains (FLCs) are important disease biomarkers in patients with plasma cell-proliferative disorders. The increasing evidence for clonal diversity... (Review)
Review
Monoclonal free light chains (FLCs) are important disease biomarkers in patients with plasma cell-proliferative disorders. The increasing evidence for clonal diversity and evolution in multiple myeloma highlights the importance of laboratory algorithms that measure both intact immunoglobulins and monoclonal FLCs, at diagnosis and when monitoring response to treatment. A particular focus in the field has been on the utility of serum FLC (sFLC) assays to replace urine electrophoresis for monoclonal FLC measurement. Due to the limited sensitivity and practical constraints of urine analysis, a serum-based algorithm of SPE and sFLC has been adopted by many laboratories as a first line screen in patients with suspected monoclonal gammopathies. This review will discuss the data supporting the use of this simple serum-based algorithm at initial diagnosis, including its utility for the rapid identification of monoclonal FLC in the setting of unexplained acute kidney injury, and provide a comprehensive review of the diagnostic sensitivity of sFLC in patients with multiple myeloma, AL amyloidosis and light chain deposition disease.
Topics: Clinical Laboratory Techniques; Humans; Immunoglobulin Light Chains; Paraproteinemias
PubMed: 23999048
DOI: 10.1016/j.cca.2013.08.018 -
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 -
Frontiers in Endocrinology 2023
Topics: Humans; Paraproteinemias
PubMed: 36733528
DOI: 10.3389/fendo.2023.1107283 -
Blood Cancer Journal Oct 2017Multiparameter flow cytometry (MFC) has become standard in the management of patients with plasma cell (PC) dyscrasias, and could be considered mandatory in specific... (Review)
Review
Multiparameter flow cytometry (MFC) has become standard in the management of patients with plasma cell (PC) dyscrasias, and could be considered mandatory in specific areas of routine clinical practice. It plays a significant role during the differential diagnostic work-up because of its fast and conclusive readout of PC clonality, and simultaneously provides prognostic information in most monoclonal gammopathies. Recent advances in the treatment and outcomes of multiple myeloma led to the implementation of new response criteria, including minimal residual disease (MRD) status as one of the most relevant clinical endpoints with the potential to act as surrogate for survival. Recent technical progress led to the development of next-generation flow (NGF) cytometry that represents a validated, highly sensitive, cost-effective and widely available technique for standardized MRD evaluation, which also could be used for the detection of circulating tumor cells. Here we review current applications of MFC and NGF in most PC disorders including the less frequent solitary plasmocytoma, light-chain amyloidosis or Waldenström macroglobulinemia.
Topics: Flow Cytometry; Humans; Paraproteinemias
PubMed: 29053157
DOI: 10.1038/bcj.2017.90 -
Blood Sep 2010Plasma cell dyscrasias are frequently encountered malignancies often associated with kidney disease through the production of monoclonal immunoglobulin (Ig).... (Review)
Review
Plasma cell dyscrasias are frequently encountered malignancies often associated with kidney disease through the production of monoclonal immunoglobulin (Ig). Paraproteins can cause a remarkably diverse set of pathologic patterns in the kidney and recent progress has been made in explaining the molecular mechanisms of paraprotein-mediated kidney injury. Other recent advances in the field include the introduction of an assay for free light chains and the use of novel antiplasma cell agents that can reverse renal failure in some cases. The role of stem cell transplantation, plasma exchange, and kidney transplantation in the management of patients with paraprotein-related kidney disease continues to evolve.
Topics: Humans; Kidney Diseases; Paraproteinemias
PubMed: 20462963
DOI: 10.1182/blood-2010-03-258608 -
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 -
Clinics in Laboratory Medicine Dec 2017Plasma cell dyscrasia (PCD) is a heterogeneous disease that has seen a tremendous change in outcomes due to improved therapies. Over the past few decades,... (Review)
Review
Plasma cell dyscrasia (PCD) is a heterogeneous disease that has seen a tremendous change in outcomes due to improved therapies. Over the past few decades, multiparametric flow cytometry has played an important role in the detection and monitoring of PCDs. Flow cytometry is a high-sensitivity assay for early detection of minimal residual disease (MRD) that correlates well with progression-free survival and overall survival. Before flow cytometry can be effectively implemented in the clinical setting, sample preparation, panel configuration, analysis, and gating strategies must be optimized to ensure accurate results. Current consensus methods and reporting guidelines for MRD testing are discussed.
Topics: Flow Cytometry; Humans; Multiple Myeloma; Neoplasm, Residual; Paraproteinemias
PubMed: 29128071
DOI: 10.1016/j.cll.2017.08.001 -
Postgraduate Medical Journal Apr 2007A paraprotein is a monoclonal immunoglobulin or light chain present in the blood or urine; it is produced by a clonal population of mature B cells, most commonly plasma... (Review)
Review
A paraprotein is a monoclonal immunoglobulin or light chain present in the blood or urine; it is produced by a clonal population of mature B cells, most commonly plasma cells. In individuals aged >50 years the incidence of a paraprotein is 3.2%. Plasma cell disorders can be considered as a spectrum of conditions ranging from monoclonal gammopathy of undetermined significance (MGUS), through asymptomatic, to symptomatic myeloma. MGUS is defined by a low level of paraprotein <30 g/l, bone marrow plasma cells <10% and the absence of myeloma related organ or tissue damage (predominantly renal, skeletal or bone marrow impairment.) MGUS requires no therapy and the overall risk of progression to myeloma is 1% per year. Myeloma remains incurable with a median survival of 3-4 years; autologous stem cell transplant can prolong survival, if appropriate. Thalidomide in combination with dexamethasone has an emerging role in the treatment of myeloma.
Topics: Anemia; Diagnosis, Differential; Diphosphonates; Humans; Hypercalcemia; Infections; Kidney Diseases; Multiple Myeloma; Pain; Paraproteinemias; Prognosis; Referral and Consultation
PubMed: 17403946
DOI: 10.1136/pgmj.2006.054627 -
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 -
Turkish Journal of Haematology :... Dec 2017Multiple myeloma (MM) is one of the most important clonal malignant plasma cell disorders and renal involvement is associated with poor prognosis. Although there are... (Review)
Review
Multiple myeloma (MM) is one of the most important clonal malignant plasma cell disorders and renal involvement is associated with poor prognosis. Although there are several reasons for renal impairment in MM, the main cause is the toxic effects of monoclonal proteins. Although cast nephropathy is the best known and unchallenged diagnosis for hematologists and pathologists, the renal effects of monoclonal gammopathy can be various. Monoclonal gammopathy of renal significance was proposed by the International Kidney and Monoclonal Gammopathy Research Group for renal lesions in monoclonal gammopathy in recent years. Renal lesions in monoclonal gammopathy can be grouped as follows: light chain (cast) nephropathy, acute tubular injury/necrosis, tubulointerstitial nephritis, amyloidosis, monoclonal Ig deposition diseases, immunotactoid glomerulopathy, type I cryoglobulinemia, proliferative glomerulonephritis with monoclonal IgG deposits, C3 glomerulopathy with monoclonal gammopathy, and crystal-storing histiocytosis, considering the previous and new terminology. In this study, renal involvement of monoclonal gammopathies, in terms of previous and new terminology, was reviewed.
Topics: Amyloidosis; Animals; Humans; Kidney; Kidney Diseases; Multiple Myeloma; Paraproteinemias; Plasma Cells
PubMed: 28832010
DOI: 10.4274/tjh.2017.0197