What is Hevylite?
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 ie 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. Immunisation 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 analysers.
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-tumour 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.
| Description | Pack | Code |
|---|---|---|
| Hevylite IgA Kappa BN™II kit Hevylite IgA Lambda BN™II kit |
50 test 50 test |
NK623.T** NK624.T** |
| NEW Hevylite IgG Kappa BN™II kit NEW Hevylite IgG Lambda BN™II kit |
50 test 50 test |
NK621.T** NK622.T** |
| NEW Hevylite IgA Kappa SPAPLUS™ kit NEW Hevylite IgA Lambda SPAPLUS™ kit |
50 test 50 test |
NK623.S** NK624.S** |
* More kits in the range will become available late 2010.
** Please enquire regarding the current FDA status
BN™II is a trademark of Siemens Healthcare Diagnostics Inc.
SPAPLUS™ is a trademark of The Binding Site Group Ltd, Birmingham, UK.
