Kappa Free Light Chains in Cerebrospinal Fluid of Patients with Identified Oligoclonal Immunoglobulin G.

BACKGROUND: Production of kappa free light chains (KFLC) represents a part of humoral immune response, along with the synthesis of intrathecal immunoglobulins. Increased concentrations of immunoglobulin G light chains, kappa and lambda chains, were identified through research of numerous diseases of central nervous system. The qualitative method of isoelectric focusing (IEF) followed by immunofixation currently represents the accepted standard in identifying oligoclonal bands (OCB), but establishing a sensitive immunonephelometric method for quantification of kappa free light chains (KFLC) in cerebrospinal fluid (CSF) has paved a way for new diagnostic possibilities. Andersson classified the pattern types of OCB, ranging from type 1 to type 5, wherein types 2 and 3 indicate intrathecal synthesis. Our aim was to determine KFLC in CSF of patients with clinically isolated syndrome (CIS) who had presented with type 2 and type 3 OCB, to determine if there is a difference in concentrations between those two groups and to establish a borderline value of KFLC which would enable differential diagnostics.

SUBJECTS AND METHODS: 70 patients, who underwent lumbar punction for CSF analysis and had their blood sampled through the cubital vein, participated in the study. Patients were classified according to Andersson as type 2 or type 3, which besides adulthood, represented the inclusion criteria. The average age of patients classified as type 2 was 36 years, and those classified as type 3 was 39 years, where it is evident that there was not a statistically significant difference (p=0.0685). We used a qualitative electrophoretic technique of IEF with agarose gel followed by immunofixation, and a quantitative immunonephelometric method. All results were interpreted on a level of statistic significance of p<0.05.

RESULTS: CSF KFLC concentrations in type 3 were statistically and significantly elevated with regard to type 2 (Mann-Whitney test, p=0.0430). The median for KFLC in type 2 was 0.9 mg/L, while the median for KFLC in type 3 was 2.71 mg/L, and the detection limit for both types was 0.18 mg/L. We used a statistical ROC curve to determine that KFLC concentration can be used for differential diagnostics, meaning it can discriminate type 2 from type 3 with clinical sensitivity of 61% and clinical specificity of 71% (AUC=0.641) (p=0.037).

CONCLUSION: Despite the obtained statistically significant differences in concentrations of KFLC between types of OCBs and ROC analysis results, determination of KFLC by a nephelometric method, insufficiently strong clinical sensitivity and specificity does not justify abandonment of IEF method followed by immunofixation.