Indicazioni per il corretto impiego delle indagini biochimiche nelle gammopatie monoclonali con particolare riferimento alla determinazione delle catene leggere libere delle immunoglobuline nel siero

Recommendations for use of biomarkers in monoclonal gammopathies with special reference to serum free light chain measurements. Monoclonal gammopathies (MG) are a group of disorders characterized by the proliferation of one plasma cell clone, which produces a monoclonal protein identified by serum proteins electrophoresis as a homogeneous band defined monoclonal component (MC). Multiple myeloma constitutes the prototype of malignant MG, but most frequently MCs refer to MG of undetermined significance (MGUS). Serum and urinary protein electrophoresis and immunofixation (IFE) are the only analytical techniques able to identify an immunoglobulin as monoclonal permitting to diagnose, quantify and type the MC with a sensitivity close to 100%. Serum free light chain (fLC) determination through kappa/lambda ratio calculation is a sensitive biomarker of clonal expansion recommended for diagnosis and follow-up of light chain and non-secretory myelomas. In the AL-amyloidosis diagnosis, the fLC assay shows ~85-90% sensitivity, increasing to 95% when associated to serum IFE and to 100% when both serum and urine IFE are added. Moreover, in the disease follow-up the decrease of circulating concentrations of amyloidogenic fLCs is associated with a prolongation of survival. An abnormal serum fLC kappa/lambda ratio has also been suggested as an independent risk factor for malignant progression in MGUS, but this application needs further validation. A diagnostic algorithm for MG by using only serum IFE and fLC assays has been evaluated showing that in 18% of myeloma patients with Bence Jones proteinuria the serum fLC kappa/lambda ratio is within the reference limits. Then, the serum fLC measurement can not replace 24 h urine protein estimation in patients with myeloma.