Assays And Clinical Applications Of Serum Free Light Chains

Object To ascertain normal range, reference intervals and diagnostic rangesfor freeκand freeλimmunoglobulin light chains(FLC) in Chineseapplying the automated immunoturbidimetric assay, and to evaluate its clinicalapplications in patients with B-cell malignant proliferative disorders.Methods Serum samples were tested using the automated immunoassay forFLCs from 63 healthy donors (age ranging from 26 to 83 ) and 85 patients withB-cell malignant proliferative disorders. Immunofixation(IFE), serum proteinelectrophoresis(SPE) and serum total light chain-assay were also applied in thepatients. Results of different methods were compared in their specificity andsensitivity.Results The lab 95% reference interval for kappa was 9.15—29.39mg/L, andfor lamda it was 15.57—33.89mg/L. The diagnostic interval for FLCκ/λwas0.96—2.38. Quantification ofκandλFLCs showed an increasing trend withaging (P 0.031＜0.05; P 0.01＜0.05). There was no correlation between FLCsand sex. The FLC value's increase was most apparent for those＞76 years ofage, while FLCκ/λdid not vary with age (P 0.803＞0.05).Compared to the healthy persons', there was no crossing and overlappingpart in the 95% reference interval forκ-FLC of the healthy people, which wasalso seen in the 95% reference interval forλ-FLC. At least in patients withB-cell malignant proliferative disorders, one of quantifications ofκandλFLCswas abnormal andκ/κratio was beyond the diagnostic interval in 97.3%patients who were identified but not treated yet. None responsers, partialresponsers and relapse patients had abnormal FLCκ/λratios. The standardserum IFE method showed an agreement of 86.4% but a sensitivity of only76.7% and was 97.4% specific when compared to the serumκ-FLCturbidimetric assay for detectingκ-type monoelonal proteins. It was provedthat the serumκ-FLC assay was more sensitive than the IFE method bychi-square test (P＜0.01). While in serumλ-FLC assay, agreement percentage,sensitivity, specificity for the IFE method were 74.1%, 62.5% and 100% respectively in detecting monoclonal proteins. It was proved that the serumturbidimetric assay was more sensitivity and positive rate than the IFE methodby chi-square test (P＜0.01). When a serum M protein existed, the patients'FLC value were all increased, while the patients with B-cell malignantproliferative disorders without M protein always had FLC values increased too.Conclusions 1. Serum FLCs increased with population age, but the ratio ofFLC did not exhibit an age-dependent trend. Detection and quantification ofmonoclonal FLCs by turbidimetry were more sensitive and specific andaccurate than IFE, SPE and serum total light chain-assay.2. The ratio of FLC was valuable in diagnostic criterion of multiple myelomaand was also an important aspect in assessing the effect of treatment.3. Based on the serum IFE method, combining the FLC turbidimetric assaywould improve the diagnostic positive rate and the accuracy of monitoringprogression of B-cell proliferative disorders. The FLC turbidimetric assayshould become a regular test in the course of diagnosis and treatment formultiple myeloma.