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Freelite® is a major breakthrough for the detection and monitoring of Multiple Myeloma (MM) and other B-cell dyscrasias. Freelite® assays were developed by Binding Site to measure free kappa and free lambda immunoglobulin light chains. Our expertise in the manufacturing of antibodies has enabled us to provide a quantitative, highly specific, automated free light chain assay for serum. |
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Significant clinical evidence indicates the benefit of Freelite® serum free light chain assays in the initial screening for monoclonal gammopathies, identifying AL amyloidosis and Nonsecretory MM patients missed by conventional electrophoretic methods. Freelite® is a sensitive, specific marker of kappa and lambda free light chains (FLC) in serum and provides quantitative measurement of:
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The serum free light chain ratio is a strong indicator of monoclonality and is valuable for distinguishing monoclonal from polyclonal diseases. International Myeloma Working Group guidelines recommend the use of serum free light chain assays (Freelite®) in the initial screening algorithm of suspected multiple myeloma and related disorders.1 In a clinical chemistry publication, Katzmann et al recommends a simplification of the plasma cell dyscrasia diagnostic algorithm mentioned in current International Myeloma Working Group guidelines indicating that only serum protein electrophoresis (SPE) and Freelite®, free light chain (FLC) tests, may be needed in many cases.2 "...because of the small incremental sensitivity provided by urine studies and serum IFE, the use of PEL [SPE] plus FLC provides a simple and efficient initial diagnostic screen for the high-tumor-burden monoclonal gammopathies such as MM [multiple myeloma], WM and SMM [smoldering multiple myeloma]. Urine studies and serum IFE can be ordered more selectively." |
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Hevylite® (HLC), a new assay now available from Binding Site outside of USA. |
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Target epitopes (in black) for Hevylite® antibodies are on the constant regions between the heavy and light chains of immunoglobulin molecules.
Intact immunoglobulin molecules contain unique junctional epitopes between the heavy chain and light chain constant regions. These are the target of the Hevylite® antibodies. They can identify separately the different light chain types of each immunoglobulin class, i.e. IgGκ, IgGλ, IgAκ, IgAλ, IgMκ, IgMλ. The molecules are then measured in pairs e.g. IgGκ/IgGλ to produce ratios of involved monoclonal immunoglobulin/background uninvolved immunoglobulin concentrations, in the same manner as serum free light chain κ and λ ratios when using Freelite®.
High Specificity Hevylite® Antibodies
As with Freelite® assays, the reagents used to make the Hevylite® tests are polyclonal antibodies produced in sheep. Immunization and adsorption techniques are designed to ensure no cross-reactivity. So, for example, IgGκ reagents do not react with free κ or IgGλ, or any other immunoglobulins.
There are 4 Hevylite® epitope regions per immunoglobulin molecule - one on each side of the heavy chain / light chain contact regions and the same on the other arm of the molecule. Because there are 4 epitope regions per molecule, immune complexes readily form with immunoglobulins in the patient's serum. This is needed to produce good homogeneous immunoassays that are suitable for nephelometric and turbidimetric automated laboratory analyzers.
Heavy chain / light chain pairs of IgG, IgA and IgM molecules showing the target epitopes for Hevylite® immunoassays in black
Limitations of Immunoglobulin Measurements
Typical analytical tests for monoclonal gammopathies are serum protein electrophoresis (SPE or SPEP) with scanning densitometry and/or immunofixation electrophoresis (IFE) together with serum free light chain immunoassays. While SPE is a simple, low cost test, it is not very sensitive and quantification of proteins at low concentrations (1-3g/L) is inaccurate.
This is particularly apparent for monoclonal IgA since its anodal electrophoretic migration positions it over other bands such as transferrin. Improved sensitivity is achieved with IFE but IFE is a non-quantitative assay. Nephelometry is also used for immunoglobulin measurements and is analytically accurate down to low concentrations. However, patients' samples also contain non-tumor polyclonal immunoglobulins of both κ and λ types that are included in the analysis. This means results are clinically inaccurate at normal serum concentrations.
Furthermore, assessments of monoclonal IgG are unreliable because of variable catabolism as FcRn recycling receptors that bind albumin and IgG become saturated or reduced by chemotherapy.
- Dispenzieri A, et al. International Myeloma Working Group guidelines for serum-free light chain analysis in multiple myeloma and related disorders. Leukemia 2009; 23:215-224
- Katzmann J, et al. Screening Panels for Detection of Monoclonal Gammopathies.
Clin Chem 2009; 55:1517-1522
 Bradwell AR. Serum Free Light Chain Analysis (Plus Hevylite®) 5th Edition 2008, Chapter 32, 275-285
Available to order for $75. Please contact your local office or distributor. |
