Disease modifying drugs modulate endogenous secretory receptor for advanced glycation end-products, a new biomarker of clinical relapse in multiple sclerosis

Objectives: This study is one in a series measuring RAGE axis (receptor for advanced glycation end products, its isoforms, and ligands) and its potential as a biomarker in multiple sclerosis (MS) We evaluated serum levels of the endogenous secretory RAGE (esRAGE) in MS patients and assessed the relationship between esRAGE levels and the use of disease modifying drugs (DMDs), and between esRAGE levels and indicators of MS disease severity Method: esRAGE serum levels were compared between 98 MS patients and 34 healthy controls (HCs) using ELISA Results: esRAGE serum levels were similar between MS and HCs DMD-treated patients had higher esRAGE serum levels than DMD-naïve patients (395.7 ± 38.6 pg/ml vs 299.2 ± 20.1 pg/ml, P = 0.02) DMD-naïve, primary progressive (PP) patients had higher esRAGE serum levels, than relapsing remitting (RR) (P = 0.02) and secondary progressive (SP) (P = 0.04) patients; RRMS patients in clinical relapse had lower esRAGE serum levels than clinically stable patients (219.7 ± 30.0 pg/ml vs 338.2 ± 31.6 pg/ml, P = 0.02) In a univariate regression analysis of DMD-naïve MS patients, esRAGE serum levels inversely correlated with the rate of clinical relapse ( r= - 0.44, P = 0.006), MS severity scale (MSSS) ( r= - 0.32, P = 0.03), and expanded disability status scale (EDSS) ( r= - 0.251, P = 0.07) Conclusion: esRAGE serum levels are modulated by DMDs The serum levels may be a useful biomarker of MS clinical relapse.