CSF Kappa Free Light Chains: Cutoff Validation for Diagnosing Multiple Sclerosis

Ruba S. Saadeh, Sandra C. Bryant, Andrew McKeon, Brian Weinshenker, David L. Murray, Sean J. Pittock, Maria Alice V. Willrich

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: To determine and validate a cerebrospinal fluid (CSF) κ (KCSF) value statistically comparable to detection of CSF-specific oligoclonal bands (OCB) to support the diagnosis of multiple sclerosis (MS). Patients and Methods: A total of 702 retrospective and 657 prospective paired CSF/serum samples from residual waste samples of physician-ordered OCB tests were obtained and tested for KCSF at Mayo Clinic. Charts were reviewed by a neurologist blinded to KCSF results. Specificity and sensitivity for MS diagnosis were evaluated to establish a diagnostic cutoff value for KCSF in the retrospective cohort and then validated in the prospective cohort. Results: Retrospective and prospective subgroups, respectively, included MS (n=85, 70), non-MS (n=615, 585), and undetermined diagnosis (excluded, n=2, 2). The retrospective data established a KCSF cutoff value of 0.1 mg/dL to be comparable to OCB testing. In the retrospective subgroup, KCSF vs OCB sensitivities for diagnosis of MS were 68.2% vs 75.0% (P=.08) and specificities were 86.1% vs 87.6% (P=.27). The KCSF area under the receiver operating characteristic curve was 0.772 (95% CI, 0.720 to 0.824), and for OCB was 0.813 (95% CI, 0.764 to 0.861). The prospective cohort was then used to validate the diagnostic KCSF value of 0.1 mg/dL; KCSF vs OCB sensitivities were 78.6% for both (P>.99) and specificities were 87.1% vs 89.4% (P=.09). Conclusion: The KCSF value of 0.1 mg/dL is a valid alternative to OCB testing, offering a standardized quantitative measure, eliminating human error, reducing cost and turnaround time, with no significant difference in sensitivity and specificity. This study provides class I evidence that a KCSF value of 0.1 mg/dL can be used in place of OCB testing to support the diagnosis of MS.

Original languageEnglish (US)
Pages (from-to)738-751
Number of pages14
JournalMayo Clinic proceedings
Volume97
Issue number4
DOIs
StatePublished - Apr 2022

ASJC Scopus subject areas

  • Medicine(all)

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