Mouse Anti-Human Kappa Light Chain Hybridoma [252QG22]

Objective To investigate the hypothesis that free light chain (FLC) sera levels could serve as a biomarker for myasthenia gravis (MG), especially for the subgroups of seronegative MG and ocular MG. Methods Sera from 73 patients with MG (20 seronegative for antiacetylcholine receptor [AChR] and anti-muscle-specific kinase and 53 positive for anti-AChR, which were clinically divided into 24 patients with ocular type, 45 with generalized type, and 4 with unequivocal clinical manifestation) and 49 healthy controls were studied for kappa FLC and lambda FLC levels with the Freelite human FLC kits. Results The kappa but not the lambda levels of FLC were significantly increased in the patients with MG, including those with double seronegative MG and ocular MG, compared with the healthy controls. The specificity for double seronegative MG and ocular MG were both 98.0% when kappa FLC was >= 25.0 mg/L. Increased kappa FLC levels were not affected by the patient's sex, age at MG onset, the presence of thymic pathology, or different treatments. Conclusions Elevated serum kappa FLC may serve as a biomarker for MG in suspected patients who are double seronegative and in those with only ocular manifestations when serology is inconclusive. Classification of evidence This study provides Class III evidence that high kappa FLC levels distinguished patients with MG, including those who were double seronegative, from healthy controls.

Background: The analysis of serum free light chains (FLCs) is clinically relevant for the diagnosis and therapeutic management of clonal plasma cell disorders. This study compares the performance of monoclonal and polyclonal FLC kappa and lambda assays in clinical samples determined in a single academic center. Methods: Serum FLCs were analyzed from 102 patients using the Freelite (Binding Site) and N Latex (Siemens) assays on the BN ProSpec System (Siemens). When available, data for protein electrophoresis, immunofixation, C-reactive protein, and estimated glomerular filtration rate (eGFR) were combined with FLC results to evaluate performance. Results: Method evaluation showed acceptable imprecision and inaccuracy measures of <4.4% and 12.9%, respectively. Poor agreement between the methods was observed, including constant and proportional bias and poor correlation (Kendall tau, 0.671-0.901). The N Latex assay was not affected by the renal impairment estimated by eGFR, unlike the FLC kappa/lambda ratio results by the Freelite assay. With the Freelite assay, 98% of putative controls without monoclonal gammopathy (n = 42) showed a kappa/lambda ratio that was above the median of the standard diagnostic range or renal diagnostic range. A shift toward highe kappa/lambda ratios was also observed when retrospective data between 2011 and 2017 were compared. Conclusions: Unlike the Freelite assay, kappa/lambda ratios analyzed with the N Latex assay were not affected by renal failure. Both methods showed acceptable performances using nephelometry, but they were poorly correlated. A shift toward kappa/lambda ratios might impair the specificity of borderline increased kappa/lambda results. This should be considered when interpreting FLC kappa and lambda results.