Kappa free light chains in cerebrospinal fluid to identify patients with oligoclonal bands

• Published in: European journal of neurology Vol. 25; no. 9; pp. 1134 - 1139
• Main Authors: Süße, M., Hannich, M., Petersmann, A., Zylla, S., Pietzner, M., Nauck, M., Dressel, A.
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.09.2018
• Subjects: Adult; Aged; Binding sites; Central nervous system; Cerebrospinal fluid; cerebrospinal fluid analysis; Chains; Cohort Studies; Diagnostic systems; Female; Health care; Humans; Immunoglobulin G; Immunoglobulin G - biosynthesis; Immunoglobulin kappa-Chains - cerebrospinal fluid; Immunoglobulins; Immunologic Factors - cerebrospinal fluid; intrathecal immunoglobulin synthesis; kappa free light chains; Latex; Light chains; Male; Middle Aged; Multiple sclerosis; Multiple Sclerosis - cerebrospinal fluid; Multiple Sclerosis - diagnosis; Multiple Sclerosis - immunology; Nephelometry; Nephelometry and Turbidimetry; oligoclonal bands; Oligoclonal Bands - cerebrospinal fluid; Patients; Predictive Value of Tests; Prospective Studies; Reproducibility of Results; ROC Curve; Sensitivity; Sensitivity and Specificity; Synthesis; intrathecal immunoglobulin synthesis; kappa free light chains; cerebrospinal fluid analysis; oligoclonal bands
• ISSN: 1351-5101; 1468-1331; 1468-1331
• DOI: 10.1111/ene.13667

Background and purpose The gold standard for detection of intrathecal immunoglobulin synthesis is the measurement of oligoclonal bands (OCB). In the diagnosis of multiple sclerosis, the kappa free light chains (KFLC) index has a similar sensitivity and specificity as OCB. This study investigated whether determination of the KFLC index could be used to predict the presence of OCB. Methods The KFLC index was determined prospectively from 295 paired serum and cerebrospinal fluid samples. KFLC were determined by nephelometry using the N Latex FLC kappa kit (Siemens Healthcare Diagnostics Products GmbH) on the BN Prospec analyzer (Siemens Healthcare Diagnostics Products GmbH) (cohort I). A cut‐off value was determined using receiver operating characteristic analysis in relation to OCB positivity. These results were validated prospectively in 96 samples (cohort II) as well as retrospectively in samples of 46 patients known to be OCB positive (cohort III). We also compared the agreement of two commercially available nephelometric KFLC assays. Results In cohort I, a KFLC index of 3.61 yielded 100% sensitivity and 88% specificity. Prospective validation of this cut‐off value in cohort II showed 92% sensitivity and 96% specificity. In cohort III, a sensitivity of 93% was achieved. Comparison of Siemens and Binding Site (Birmingham, UK) assays revealed good agreement (r2 = 0.86). Conclusions The KFLC index with a cut‐off value of 3.61 had high diagnostic accuracy to predict immunoglobulin G synthesis via OCB analysis. Determination of the KFLC index provided a quantitative parameter that could be used as an initial diagnostic step in inflammatory central nervous system disorders before measuring OCB.