Optimized Kappa-Index Test Protocol to Detect Intrathecal Immunoglobulin Synthesis in Multiple Sclerosis

Area of Science:

• Neurology
• Immunology
• Clinical Chemistry

Background:

• Kappa free light chain (KFLC)-based Kappa-index (K-index) shows promise in detecting intrathecal immunoglobulin synthesis, potentially serving as an alternative to oligoclonal banding (OCB).
• Current diagnostic protocols exhibit variability in K-index cutoffs, necessitating further research to optimize its diagnostic utility.

Purpose of the Study:

• To compare different approaches for optimizing the K-index assay for diagnostic utilization in neuroinflammatory diseases.
• To evaluate the K-index's effectiveness in detecting intrathecal immunoglobulin synthesis compared to OCB.

Main Methods:

• Analysis of 432 paired cerebrospinal fluid (CSF)/serum samples from patients with multiple sclerosis (MS), clinically isolated syndrome (CIS), and other neuroinflammatory diseases (non-MS).
• Measurement of K-index using the Optilite platform and OCB via isoelectric focusing on the Hydrasys platform.
• Comparison of K-index values between OCB-positive and OCB-negative groups, and across different disease cohorts (MS, CIS, non-MS).

Main Results:

• OCB-positive cases demonstrated significantly higher K-index values compared to OCB-negative cases.
• The MS group exhibited a higher K-index than CIS (p=0.0066) and non-MS (p<0.0001) groups.
• Established K-index cutoffs for differentiating MS from CIS (80.9) and non-MS (61.4). Optimized cutoffs using the limit of detection (LOD) with 95% sensitivity and specificity were <4.45 (negative) and >12.92 (positive).

Conclusions:

• Published K-index cutoffs vary due to inconsistent handling of CSF KFLC results below the LOD.
• A reflex approach, considering samples within a K-index gray area for OCB verification and classifying CSF KFLC below LOD as negative, represents the most efficient laboratory algorithm.
• The K-index may hold prognostic value in MS, warranting further investigation.