Rapid detection of serum free light chains by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

Introduction: Serum free light chain (FLC) measurements are increasingly prominent for patients with plasma cell disorders (PCDs) in screening, prognostic stratification, and monitoring therapy responses. Objectives: We aimed to develop a sensitive, reliable, and accurate method for diagnosing PCDs that can notably decrease the time and cost of current methods. Methods: Here, we present a novel approach for FLC measurement using immunoenrichment on micro-affinity chromatography in combination with matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) detection. In this study, serum free kappa (κ) and free lambda (λ) light chain (LC) levels in the serum of 105 patients were compared between the nephelometric serum FLC quantification and MALDI-TOF MS detection. Results: Cohen's kappa coefficient between the MALDI-TOF MS-based method and the FLC assay revealed an almost perfect agreement in the case of normal (negative) results (κ = 0.92; 95% confidence interval (CI): 0.837 to 0.968) and a good agreement in the case of increased (positive) results (κ = 0.76; 95% CI: 0.608 to 0.870). In Spearman's correlation analysis, the best correlation was found between serum free κ/λ ratios (r = 0.628, 0.496 to 0.732; p <0.0001). Our method showed sensitivity (92.5%) and specificity (76.3%) for discrimination between the κ/λ FLC ratio compared to the serum FLC assay. Conclusion: The proposed method can significantly contribute to diagnosing and monitoring PCDs as it can significantly be time-saving, cost-effective in FLC measurement.

Kappa/Lambda light-chain typing in Alzheimer's Disease.

BACKGROUND: Alzheimer's disease is a progressive neurodegenerative disorder characterized by memory loss and cognitive impairment. The diagnosis of Alzheimer's disease according to symptomatic events is still a puzzling task. Developing a biomarker-based, low-cost, and high-throughput test, readily applicable in clinical laboratories, dramatically impacts the rapid and reliable detection of the disease. OBJECTIVE: This study aimed to develop an accurate, sensitive, and reliable screening tool for diagnosing Alzheimer's disease, which can significantly reduce the cost and time of existing methods. METHODS: We have employed a MALDI-TOF-MS-based methodology combined with a microaffinity chromatography enrichment approach using affinity capture resins to determine serum kappa (κ) and lambda (λ) light chain levels in control and patients with AD. RESULTS: We observed a statistically significant difference in the kappa light chain over lambda light chain (κLC/λLC) ratios between patients with AD and controls (mean difference -0,409; % 95 CI:- 0.547 to -0.269; p<0.001). Our method demonstrated higher sensitivity (100.00%) and specificity (71.43%) for discrimination between AD and controls. CONCLUSION: We have developed a high-throughput screening test with a novel sample enrichment method for determining κLC/λLC ratios associated with AD diagnosis. Following further validation, we believe our test has the potential for clinical laboratories.