Diagnostic Utility of Kappa Free Light Chain Index in Adults With Inaugural Optic Neuritis

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BACKGROUND AND OBJECTIVES: A simple, quick, and reproducible procedure for distinguishing multiple sclerosis (MS), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), and neuromyelitis optica spectrum disorder (NMOSD) at inaugural optic neuritis (ION) could be highly valuable in guiding early management. METHODS: We included all adults admitted to the MS center of Marseille for ION between March 2016 and April 2024, with CSF analysis including the kappa free light chain (K-FLC) index. Receiver operating characteristic curves were used to measure the diagnostic ability of the K-FLC index. RESULTS: Two hundred twenty-seven adults were admitted for ION; 210 (93%) had a K-FLC index measurement. MS was diagnosed in 84 (40%); clinically isolated syndrome suggestive of MS in 77 (36.5%), including 20 with future conversion to MS (CISwc); MOGAD in 26 (12.5%); NMOSD in 13 (6%); and other inflammatory disorders in 10 (5%). A K-FLC index ≥6.7 differentiated MS/CISwc from other diagnoses with specificity 86% and sensitivity 95% (area under the curve [AUC] 0.94). A K-FLC index <4.9 differentiated MOGAD from other diagnoses with specificity 63% and sensitivity 92% (AUC 0.78) and MOGAD from MS/CISwc with specificity 96% and sensitivity 92% (AUC 0.97). Among all patients, 93 (44%) had a K-FLC index <4.9: 24 of these (26%) had MOGAD and 5 (5.5%) MS/CISwc. Among the remaining patients with a K-FLC index ≥4.9 (n = 117), 2 (1.7%) had MOGAD (K-FLC index of 7.9 and 16.2) and 99 (85%) MS/CISwc. Among patients with normal MRI (n = 96), 73 (76%) had a K-FLC index <4.9: 22 of these (30%) had MOGAD, and none showed conversion to MS. Among the remaining patients with a K-FLC index ≥4.9 (n = 23), 2 (8.5%) had MOGAD and 7 (30.5%) showed conversion to MS. The K-FLC index did not differentiate NMOSD from other diagnoses and only moderately differentiated NMO from MS/CISwc (AUC 0.80). DISCUSSION: The K-FLC index is an accessible biomarker to guide early diagnosis in patients with ION. The probability of MOGAD in patients with ION and a K-FLC index ≥4.9 is low even in case of normal brain/spinal cord MRI. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for patients with ION, the K-FLC index can distinguish between MS/CISwc and MOGAD.

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