The significance of free light-chain ratio in light-chain monoclonal gammopathy of undetermined significance: a flow cytometry sub-study of the iStopMM screening study.

Light-chain (LC) monoclonal gammopathy of undetermined significance (MGUS) is a precursor of multiple myeloma (MM) and related conditions. LC-MGUS is characterized by free light-chain (FLC) levels outside defined reference intervals, indirectly indicating underlying plasma cell (PC) monoclonality. Next-generation flow cytometry (NGF) was used to evaluate clonal PC presence in bone marrow (BM) samples from individuals with LC-MGUS in the iStopMM study, aiming to assess the predictive value of the FLC ratio for clonal PC presence and its prognostic implications.

Parameter Identification for a Model of Neonatal Fc Receptor-Mediated Recycling of Endogenous Immunoglobulin G in Humans.

Salvage of endogenous immunoglobulin G (IgG) by the neonatal Fc receptor (FcRn) is implicated in many clinical areas, including therapeutic monoclonal antibody kinetics, patient monitoring in IgG multiple myeloma, and antibody-mediated transplant rejection. There is a clear clinical need for a fully parameterized model of FcRn-mediated recycling of endogenous IgG to allow for predictive modeling, with the potential for optimizing therapeutic regimens for better patient outcomes. In this paper we study a mechanism-based model incorporating nonlinear FcRn-IgG binding kinetics.

Association between urinary free light chains and progression to end stage renal disease in chronic kidney disease.

Background: Patients with chronic kidney disease (CKD) are at an increased risk of developing end-stage renal disease (ESRD). We assessed for the first time whether urinary free light chains (FLC) are independently associated with risk of ESRD in patients with CKD, and whether they offer incremental value in risk stratification.

Materials And Methods: We measured urinary FLCs in 556 patients with CKD from a prospective cohort study.

Serum IgG4 Concentration in IgG4-Related Disease.

Background: IgG4-related disease (IgG4-RD) is an immune-mediated and chronic fibroinflammatory condition that affects almost any organ and often involves multiple organs in the same patient. In this review article, we address the clinical utility of measuring serum immunoglobulin G subclass 4 concentration ([IgG4]) in IgG4-RD diagnosis and in disease monitoring.

Methods: We discuss the latest literature on the relevance of [IgG4] to the investigation and management of IgG4RDs.

Serum Free Light Chain (FLC) Analysis: A Guiding Light in Monoclonal Gammopathy Management.

Background: Monoclonal free light chains (FLCs) were first reported by Dr. Henry Bence Jones over 150 years ago in the urine of patients with multiple myeloma. Now established as important tumor markers, they aid not only in the diagnosis of monoclonal gammopathies but also in their clinical management by indicating the response to treatment and persistence of residual disease.

Serum tryptase concentration and progression to end-stage renal disease.

Background: Mast cell activation can lead to nonclassical activation of the Renin-Angiotensin-Aldosterone System. However, the relevance of this to human chronic kidney disease is unknown. We assessed the association between serum tryptase, a product of mast cell activation, and progression to end-stage renal disease or mortality in patients with advanced chronic kidney disease.

Analytical issues of serum free light chain assays and the relative performance of polyclonal and monoclonal based reagents.

Serum free light chain (FLC) assays have been incorporated into routine clinical practice and their use is recommended in international guidelines for the management of monoclonal gammopathies. Given that FLCs are not simple analytes, laboratories should be aware of potential analytical issues when using FLC assays, including antigen excess, lot-to-lot variation and non-linearity. Whilst manufacturers of monoclonal antibody-based assays claim that they overcome such issues, the evidence available to date does not support this.

Quantification of β-region IgA monoclonal proteins - should we include immunochemical Hevylite® measurements? Point.

Accurate measurement of IgA monoclonal proteins presents a significant challenge to laboratory staff. IgA heavy/light chain (Hevylite, HLC) analysis is an alternative methodology for monoclonal protein assessment, giving an independent measure of IgAκ and IgAλ concentrations. Clonality is assessed by calculating the ratio of involved immunoglobulin to background uninvolved immunoglobulin concentrations (e.

IgA kappa/IgA lambda heavy/light chain assessment in the management of patients with IgA myeloma.

Background: Accurate quantification of immunoglobulin A (IgA) monoclonal immunoglobulins by serum protein electrophoresis (SPEP) can be difficult and can impact the assessment of response among patients with multiple myeloma (MM). Therefore, there is a need to identify new assays that better reflect disease burden and response to treatment, and correlate with patient outcome. IgA Hevylite (HLC) measures IgA kappa and IgA lambda separately and provides precise quantitative measurements of the monoclonal IgA expression and polyclonal-isotype matched suppression.

Quantification of polyclonal free light chains in clinical samples using a single turbidimetric immunoassay.

Background: Elevated polyclonal serum free light chain (FLC) levels have been associated with increased mortality and disease activity in many conditions. Currently, polyclonal FLC quantification requires summation of individual FLCκ and FLCλ assays. Here we present a single assay for combined FLC (cFLC, Combylite) which reduces assay time and eliminates potential imprecision errors incurred by summating FLC assays (ΣFLC).

Serum polyclonal immunoglobulin free light chain levels predict mortality in people with chronic kidney disease.

Objective: To determine whether elevated serum polyclonal free light chain (FLC) levels predict mortality in a population of individuals with chronic kidney disease (CKD).

Patients And Methods: From January 2, 2006, through July 31, 2007, we recruited a cohort of 848 people with CKD who were not receiving renal replacement therapy and did not have monoclonal gammopathy. We measured serum kappa FLC and lambda FLC isotype levels to determine combined FLC (cFLC) levels.

Elevated serum free light chains predict cardiovascular events in type 2 diabetes.

Objective: Elevated polyclonal serum immunoglobulin free light chains (FLCs; combined FLCκ+FLCλ [cFLC]) are associated with adverse clinical outcomes and increased mortality; we investigated cFLC and cardiovascular disease (CVD) events in type 2 diabetes.

Research Design And Methods: In a cohort study of 352 south Asian patients with type 2 diabetes, serum cFLC, high-sensitivity C-reactive protein (hsCRP), and standard biochemistry were measured. CVD events over 2 years were recorded and assessed using multiple logistic regression.

Ratio of involved/uninvolved immunoglobulin quantification by Hevylite™ assay: clinical and prognostic impact in multiple myeloma.

Background: HevyLite™ is a new, recently developed method that facilitates separate quantification of the kappa- and lambda-bounded amounts of a given immunoglobulin (Ig). Using this method, we measured intact immunoglobulin (heavy/light chain; HLC) IgG-kappa, IgG-lambda, IgA-kappa, IgA-lambda individually, as well as their deriving ratios (HLCR) in a series of IgG or IgA multiple myeloma (MM) patients, to investigate and assess the contribution of these tests to disease evaluation.

Patients And Methods: HevyLite™ assays were used in sera from 130 healthy individuals (HI) and 103 MM patients, at time of diagnosis.

Activation of ASK1, downstream MAPKK and MAPK isoforms during cardiac ischaemia.

p38 MAPK is activated potently during cardiac ischaemia, although the precise mechanism by which it is activated is unclear. We used the isolated perfused rat heart to investigate the signalling pathways activated upstream of p38 during global cardiac ischaemia. Ischaemia strongly activated p38alpha but not the JNK pathway.

Serum free light chain immunoassay as an adjunct to serum protein electrophoresis and immunofixation electrophoresis in the detection of multiple myeloma and other B-cell malignancies.

Background: Protein and immunofixation electrophoresis of serum and urine are established as diagnostic aids for identifying monoclonal gammopathies. However, many patient sera sent to laboratories are not accompanied by urine samples and recent reports suggest the use of serum free light chain (sFLC) analysis in combination with serum protein electrophoresis (SPE) and immunofixation electrophoresis (lFE) could eliminate the need for urinalysis. The aim of the study was to assess the utility of sFLC measurement in addition to serum protein electrophoresis in the identification of patients with B-cell malignancies.

Assessment of monoclonal gammopathies by nephelometric measurement of individual immunoglobulin kappa/lambda ratios.

Background: Currently, monoclonal immunoglobulins are identified and quantified from bands on electrophoretic gels. As an alternative, clonality might be determined by measuring the separate light chain types of each Ig class to allow numerical assessment of Ig'kappa/Ig'lambda ratios, analogous to free light chain kappa/lambda ratios.

Methods: Using immunization, tolerization, and adsorption procedures, we prepared sheep antibodies against each of the 6 separate molecules, IgGkappa, IgGlambda, IgAkappa, IgAlambda, IgMkappa, and IgMlambda.

A new anticancer glycolipid monoclonal antibody, SC104, which directly induces tumor cell apoptosis.

A novel monoclonal antibody was raised by immunization of mice with colorectal tumor cell lines. The fusion was screened by immunohistochemistry for binding to primary colorectal tumors. Subsequent analysis on primary disaggregated colorectal tumors show that the antibody recognizes a cell surface antigen expressed by the majority of colorectal tumors.