Prognostic Value of Kappa Free Light Chain Index in patients with Primary Progressive Multiple Sclerosis

Martin Schmidauer¹Klaus Berek²Michael Auer²Gabriel Bsteh³Paola Cavalla⁴Franziska Di Pauli²Massimiliano Di Filippo⁵Florian Deisenhammer²Andreja Emersic⁶Fabian Foettinger³Lorenzo Gaetani⁵Michaela Hassler⁷Nik Krajnc³Dejan Milosavljevic⁷Markus Ponleitner³Thor Petersen⁸Stefan Presslauer⁹Igal Rosenstein¹⁰Uros Rot⁶Caroline Winther Tørring¹¹Domizia Vecchio¹²Marco Vercellino¹³Tobias Zrzavy³Anne Zinganell²Janette Walde¹⁴Harald Hegen^2*

• ¹Innsbruck Medical University, Innsbruck, Austria
• ²Medizinische Universitat Innsbruck, Innsbruck, Austria
• ³Medizinische Universitat Wien, Vienna, Austria
• ⁴Azienda Ospedaliero Universitaria Citta della Salute e della Scienza di Torino Neurologia 3, Turin, Italy
• ⁵Universita degli Studi di Perugia, Perugia, Italy
• ⁶Univerza v Ljubljani, Ljubljana, Slovenia
• ⁷Fachhochschule Campus Wien, Vienna, Austria
• ⁸Syddansk Universitet, Odense, Denmark
• ⁹Wiener Gesundheitsverbund Klinik Ottakring, Vienna, Austria
• ¹⁰Goteborgs universitet, Gothenburg, Sweden
• ¹¹Aarhus Universitetshospital, Aarhus, Denmark
• ¹²Azienda Ospedaliero Universitaria Maggiore della Carita, Novara, Italy
• ¹³Universita degli Studi di Torino, Turin, Italy
• ¹⁴Universitat Innsbruck, Innsbruck, Austria

Background: Kappa free light chain (-FLC) index is a well-established biomarker in multiple sclerosis (MS). While the prognostic value of the -FLC index has been demonstrated in early relapsing-remitting MS, its prognostic value in primary progressive MS (PPMS) has not yet been investigated. Methods: In this multicenter, retrospective cohort study patients diagnosed with PPMS with diagnostic lumbar puncture and clinical follow-up of at least 12 months were recruited through nine MS centers across five countries. At baseline, age, sex, disease duration, number of T2 hyperintense (T2L) and contrast-enhancing T1 lesions (CEL) on MRI were determined. -FLC were measured by nephelometry/turbidimetry, and -FLC index calculated as [CSF -FLC/serum -FLC]/albumin quotient. At follow-up, the occurrence of disability progression as well as the administration of disease-modifying treatment (DMT) were registered. The primary endpoint was time to disability progression. Results: A total of 121 PPMS patients were included with a median age of 53 years (25th-75th percentile: 46–59) and a balanced sex distribution (48.8% females). Multivariable Cox regression analysis revealed no significant association between the -FLC index and disability progression (Hazard ratio (HR) 1.0, p = 0.950). Prior use of DMT (HR 0.60, p = 0.023) and brain T2L >9 at baseline (HR 2.22, p = 0.026) were significantly associated with disability progression. The remaining covariates including age, sex, disease duration and CEL showed no significant associations. Conclusion: The -FLC index does not predict disability progression in PPMS, contrasting its growing role as a prognostic biomarker in relapsing MS. This highlights phenotypic differences in MS pathophysiology and underscores the need for prognostic biomarkers in PPMS.