No abstract

Development of multiple sclerosis (MS) is more prevalent in females than in males, but the underlying mechanisms are not clear. Microbial infections have been suspected as triggers of MS and it is not known whether gender differences in reactivity to environmental antigens contribute to the disease pathogenesis. We demonstrated that ACA 83-95, a mimicry epitope from Acanthamoeba castellanii for proteolipid protein (PLP) 139-151, induces clinical signs of encephalomyelitis in both male and female SJL mice. Conversely ACA 83-95-induced effector cells from males fail to induce disease in female mice. Although we found no gender differences in the frequencies of antigen-specific cells including cytokine production, PLP-specific cells induced with ACA 83-95 differed in T cell receptor vβ usage from those induced with PLP 139-151. The data suggest that cross-reactive T cell expansion occurs similarly in both males and females, but their disease-inducing ability is influenced by gender.

A definitive diagnostic test for multiple sclerosis (MS) does not exist; instead physicians use a combination of medical history, magnetic resonance imaging, and cerebrospinal fluid analysis (CSF). Significant effort has been employed to identify biomarkers from CSF to facilitate MS diagnosis; however none of the proposed biomarkers have been successful to date. Urine is a proven source of metabolite biomarkers and has the potential to be a rapid, non-invasive, inexpensive, and efficient diagnostic tool for various human diseases. Nevertheless, urinary metabolites have not been extensively explored as a source of biomarkers for MS. Instead, we demonstrate that urinary metabolites have significant promise for monitoring disease-progression, and response to treatment in MS patients. NMR analysis of urine permitted the identification of metabolites that differentiate experimental autoimmune encephalomyelitis (EAE)-mice (prototypic disease model for MS) from healthy and MS drug-treated EAE mice.