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Quantification of immunoglobulin heavy and light chain pairs

Pictogramme horloge Nicole Couprie Pictogramme horloge April 2016

Patients, who are carriers of a monoclonal gammopathy, have often been seen in our laboratories with a test request for serum IgG Kappa or IgA lambda quantification. This has left some of us baffled thinking that the analytical standpoint was to integrate the monoclonal peak onto a serum electrophoresis pattern!

It can certainly be said that it’s on the serum electrophoresis pattern that we can follow-up existing monoclonal components, however, since 2010, an alternative quantification assay for immunoglobulin heavy and light chain pairs has been made available (also known as heavy/light chains (HLC)).

The Hevylite reagents, which are made up of polyclonal antibodies, recognise the epitopes which are only found at the whole immunoglobulin heavy and light chain junction. These antibodies allow us to quantify the immunoglobulin pairs (IgG kappa/IgG lambda, IgA kappa/IgA lambda, IgM kappa/IgM lambda) by using nephelometry or turbidimetry and a ratio calculation between the monoclonal component and the residual immunoglobulins of the same class.

Within our laboratories, we have been struck by the difficulty of highlighting the migrating monoclonal peak within the beta-globulin zone (usually IgA); H. Ludwig (1) confirmed the superiority of the HLC test for the exact quantification of this type of monoclonal component when compared to electrophoresis.

Recent studies have brought to light the scientific significance of HLC assays on several planes:

  • The follow-up of myeloma cases and the evaluation of residual disease (1): the Ig kappa/Ig lambda ratio remains abnormal in 8 patients with a full response within a set of 31; the relapse could have been also identified in 3 patients before even the immunofixation positive result reappeared.
  •  Myeloma prognosis (2): by combining the HLC assay and beta-2-microglobulin assay we can constitute a stratification model for patient prognosis that is more discriminatory than the International Staging System classification.
  • Assessment of the risk of progression of an monoclonal gammopathy of undetermined significance (MGUS) in cases of myeloma (3): within the scope of MGUS for IgG lambda for example, the deletion of IgG kappa indicates an independent risk factor for pathological disease development.
  • A rapid diagnostic tool for a heavy chain disease (4): up until now, the proof of this low-frequency monoclonal gammopathy could only be determined through the use of a time-consuming manual technique known as immunoselection.

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