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 & kappa; and & lambda; FLC and & kappa;/& lambda; 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 & kappa;/& lambda; ratio than patients with earlyonset 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 & kappa;/& lambda; 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.

Automated summary

In this study, elevated FLC ratio was found in LOMG patients, suggesting aberrant clonal plasma cell function. Immunoregulatory pathways were found to be altered in MG. Further investigation on the immunoregulatory pathways in MG is needed.