Diagnostic Value of the Kappa Free Light Chain Index to Distinguish MOGAD, NMOSD, and MS.

BACKGROUND AND OBJECTIVES: The differential diagnosis between aquaporin-4-immunoglobulin G-positive neuromyelitis optica spectrum disorder (AQP4-NMOSD), myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD), and multiple sclerosis (MS) can be complex. Kappa free light chain index (KFLC-Index) emerged as an effective biomarker for distinguishing patients with MS from patients with other conditions. The main aim of this study was to assess the diagnostic performance of KFLC-Index in differentiating MOGAD, AQP4-NMOSD, and MS and to compare it with CSF-restricted oligoclonal bands (OCB) performance. METHODS: We conducted a retrospective case-control study involving 18 French centers through our national NOMADMUS database. Patients were eligible if they received MOGAD or AQP4-NMOSD diagnosis and if OCB status and KFLC-Index levels were available or could be measured retrospectively. As a comparator, we included a group of patients with MS from the Lyon center. RESULTS: We included 303 patients with 140 MOGAD, 37 AQP4-NMOSD, and 126 MS. The sex ratio F/M was 1/1 in the MOGAD group, 5/1 in the NMOSD group, and 4/1 in the MS group. The median age was 38 years in the MOGAD group, 52 in the NMOSD group, and 32 in the MS group. The median KFLC-Index (interquartile range) was the lowest in the MOGAD group (0.60 [0.33-2.09]) with 71% of undetectable CSF-KFLC, intermediate in the NMOSD group (8.85 [3.04-16.78]), and the highest in the MS group (49.90 [16.31-113.39]). KFLC-Index had very good diagnostic performance in differentiating MOGAD from MS (area under the curve [AUC] 0.93, 95% CI 0.9-0.96) with an optimal threshold of 5.7 (95% CI 4.74-6.85), a sensitivity of 0.89 (0.83-0.94), and a specificity of 0.89 (0.83-0.94). KFLC-Index had good performance in differentiating NMOSD from MS (AUC 0.82, 95% CI 0.74-0.88) and MOGAD from NMOSD (AUC 0.77, 95% CI 0.69-0.86). KFLC-Index did not significantly outperformed OCB in separating MOGAD from MS and NMOSD from MS; however, the combination of the 2 tests was more performant than used separately. DISCUSSION: KFLC-Index is a valuable tool in distinguishing MS from AQP4-NMOSD and MOGAD and provides additional information to that given by OCB. We suggest that KFLC-Index as an additional supporting criterion for the differential diagnosis between MOGAD and MS.