Search for new biomarkers of pediatric multiple sclerosis: Application of immunoglobulin free light chain analysis

Identifying new biomarkers is needed to overcome the diagnostic difficulties of pediatric multiple sclerosis (MS). Recently, we developed a new technique including CSF analysis of free light chain (FLC) monomers and dimers, which can improve diagnosis of adult MS. The present study has been designed to evaluate the utility of our technique for MS diagnosis in children. Patients with MS (n=21) and non-MS demyelinating or inflammatory neurological disorders (n=35) participated in the study. MS diagnosis was based on clinical and magnetic resonance imaging (MRI) findings. Western blot analysis was applied to examine FLC in the patients' CSF and serum. FLC indices for FLC monomer and dimer levels and κ/λ ratios were estimated. The samples were also analyzed by oligoclonality test. The study revealed abnormally elevated levels of κ-FLC monomers and dimers in the CSF of 10 MS patients ("κ-type MS"). Increased amounts of λ dimers were found in six MS cases ("λ-type MS"), while high levels of both κ and λ FLC ("mixed type MS") were documented in three MS cases. MRI and clinical assessment showed a more aggressive disease form for the "mixed" and "λ-type" cases. Our method demonstrated higher sensitivity (90.5%) and specificity (91.4%) for discrimination between MS and non-MS patients, as compared to oligoclonality test (81% and 65.7%, respectively). The proposed method may significantly contribute to diagnosis and prognosis of pediatric MS.