Putative predictive power of baseline cerebrospinal fluid dipeptidyl peptidase-4 on the conversion to secondary progressive multiple sclerosis

Background Dipeptidyl peptidase-4 (DPP4) has many inflammation-related functions such as T cell activation, and complement activation and is recognized as a putative pathogenic factor in multiple sclerosis (MS). Our aim was to analyze whether baseline cerebrospinal fluid (CSF) levels of DPP4 and DPP4-induced complement breakdown byproducts might predict MS progression.Methods Levels of DPP4, factor C3a (C3a), factor C4a (C4a), factor Ba (Ba) and soluble membrane attack complex (sMAC) were measured by ELISA in CSF obtained during the first clinical attack of 80 MS patients. The association between CSF markers and disability progression was assessed by regression analyses.Results Fourteen of 80 patients had converted to secondary progressive MS (SPMS) in a follow-up period of 9.4 ± 5.1 years. As compared to patients preserving relapsing-remitting MS (RRMS) status, SPMS-convertors showed significantly higher baseline CSF DPP4 (p = 0.035) and Ba (p = 0.013) levels. Receiver operating characteristic analysis indicated baseline CSF DPP4 level to be associated with increased risk of SPMS conversion (p = 0.026, AUC = 0.691, 95% CI = 0.6–0.8). Cox regression analysis showed that after adjustment for onset age and duration of disease, DPP4 levels were associated with increased risk for conversion to SPMS (p = 0.040), and baseline CSF Ba levels were associated with time to disability progression (EDSS 3.0) (p = 0.031).Conclusions Baseline CSF DPP4 levels may predict the emergence of SPMS at the early stage of disease, whereas baseline Ba levels appear to be associated with earlier progression of MS.