A skewed ratio of free light chains is more common in patients with late-onset than early-onset myasthenia gravis.

Myasthenia gravis (MG) is an autoantibody-mediated neuromuscular disease with an unpredictable clinical course. Serum free light chains (FLCs) have risen as a promising biomarker for MG, but their role in different subtypes of MG and in predicting disease progression is still uncharted. We investigated plasma from 58 generalized MG patients during post-thymectomy follow-up to determine κ and λ FLC and κ/λ ratio. In a subcohort of 30 patients, we examined the expression of 92 proteins associated with immuno-oncology using Olink. We further studied the ability of FLCs or proteomic markers to differentiate disease severity. Patients with late-onset MG (LOMG) displayed significantly higher mean κ/λ ratio than patients with early-onset MG (P = 0.004). Inducible T-cell co-stimulator ligand (ICOSLG), matrix metalloproteinase 7 (MMP7), hepatocyte growth factor (HGF), and arginase 1 (ARG1) were differentially expressed in MG patients compared to healthy controls. There were no significant associations between clinical outcomes and FLCs or the assayed proteins. In conclusion, an elevated κ/λ ratio suggests long-lasting aberrant clonal plasma cell function in LOMG. Immuno-oncology-related proteomic analysis showed alterations in immunoregulatory pathways. Our findings pinpoint the FLC ratio as a biomarker for LOMG and call for further investigation of the immunoregulatory pathways in MG.