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Serum assay of immunoglobulin (Ig) free light chains (FLC)

Pictogramme horloge Laurence Guis Pictogramme horloge May 2015

During the synthesis of immunoglobulins, light chains (LC) are produced the same time as heavy chains (HC), thus enabling the constitution of a functional immunoglobulin. Physiologically, there is a slight excess of free light chains (FLC), which is eliminated by the kidneys. In a disease situation, due to the proliferation of plasma sites, there will be an excess production of FLC.

  • If the proliferation is POLYCLONAL (autoimmune diseases, infections, cancers, etc.), the FLCs produced will be polyclonal.
  • If the proliferation is MONOCLONAL (myeloma, amyloidosis), a single type of LC will be producing excess and the FLCs will be monoclonal.

The FLCs can be assayed by nephelometry or turbidimetry. This assay allows better support for the diagnosis, follow-up and prognosis of certain plasma cell disorders. In AL amyloidosis, the essay will be useful for diagnosis, follow-up, and as a criterion of treatment response. In the context of myeloma (light-chain, non-secreting, poorly secreting), plasma site owners and light-chain to position diseases, it will be useful in monitoring the disease. The assay is intended as an early factor treatment response or relapse; the progress of FLC levels is associated with a five-year survival of 88% for patients with an FLC level reduced by more than 50% and of 39% for those with an FLC level reduced by less than 50%. The indications in the monitoring of whole-Ig plasma-cell disorders (myeloma, Waldenström’s macroglobulinemia, MGUS) are less clear.

NB: the assay measures total FLC, monoclonal AND polyclonal. It is therefore necessary to interpret the results in their overall context: electrophoresis, immunofixation of serum proteins (confirmation of monoclonal character), so as to best adapt the diagnostic process and to identify any analytical interferences:

  • Risk of underestimation by a zone effect linked to an excess of antigen
  • Risk of overestimation in case of polymerisation of the monoclonal FLCs or fixation of the proteins (alpha1-antitrypsin).

The recommendations indicate the parallel assay of both FLCs (? AND ?) so as to establish an FLC?/FLC? ratio that would be an indicator of monoclonality. In the case of an inflammatory syndrome or kidney disease associated with plasma-cell disorder, the level of FLCs would increase (monoclonal FLCs and also polyclonal FLCs) and so the ratio and the difference between the assays of the two FLCs would be informative for monitoring.

NB: On the other hand, it is NOT RECOMMENDED to carry out the assay of URINARY FLCs, which is never a good reflection of the tumour mass. Renal monitoring should be carried out by assay of 24h-urine albumin and protein levels, electrophoresis and immunofixation of urinary proteins.

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