Serum Metabolic Profile in Multiple Sclerosis Patients

Abstract

Multiple sclerosis (MS) is a progressive demyelinating process considered as an autoimmune disease, although the causes of this pathology have not been yet fully established. Similarly to other neurodegenerations, MS is characterized by a series of biochemical changes affecting to different extent neuronal functions; great attention has been given to oxidative/nitrosative stress and to alterations in mitochondrial functions. According to previous data, MS patients show significant changes in the circulating concentrations of different metabolites, although it is still unclear whether uric acid undergoes to decrease, increase, or no change under this pathological condition. In this study, we report the serum metabolic profile in terms of purines, pyrimidines, creatinine, malondialdehyde, ascorbic acid, nitrite, and nitrate in a group of 170 MS patients. The results show increase in circulating uric acid and other oxypurines (hypoxanthine and xanthine), as well as in uridine and β-pseudouridine. The concomitant increase in circulating creatinine, malondialdehyde, nitrite, and nitrate, and decrease in ascorbic acid, demonstrates that MS induces alteration in energy metabolism and in oxidants/antioxidants balance that can be monitored in serum of MS patients.

Lactate at the crossroads of metabolism, inflammation, and autoimmunity

“…A mitochondrial dysfunction with defects of mitochondrial respiratory chain complex IV (cytochrome c oxidase) has been found in some active lesions of relapsing remitting MS patients [71]. Furthermore, a metabolomic study has revealed changes in MS patient serum levels of different metabolites and oxidants/antioxidants unbalance compared to healthy controls [72]. Moreover, increased levels of both glutamine and glutamate have been described.…”

“…Moreover, increased levels of both glutamine and glutamate have been described. Glutamate concentration correlates with disease severity, and glutamine is critically required for naive CD4 + T-cell differentiation toward Th1 and Th17 proinflammatory T cells [72].…”

“…Moreover, increased levels of both glutamine and glutamate have been described. Glutamate concentration correlates with disease severity, and glutamine is critically required for naive CD4 + T-cell differentiation toward Th1 and Th17 proinflammatory T cells [72].De Rosa et al [73] recently found that glycolysis is required for the expression of FOXP3 (forkhead box P3), a master regulator in the development and suppressive function of Treg cells. MS subjects display impaired rates of glycolysis, which in turn determines altered peripheral Treg-cell generation and functions [73].…”

Oxidative Stress-Related Biomarkers in Multiple Sclerosis: A Review

“…Most studies reported significantly higher mean tNOx in RRMS compared to control groups, in acute relapse and in remission [16][17][18][19][20][21][22][23]. Most noteworthy is Tavazzi et al's study [16] of a large cohort of 113 RRMS patients in whom serum tNOx levels were significantly higher (p<0.001) in RRMS patients than in health controls. Three studies described no significant difference but were heterogeneous as to the MS disease phenotype, and none considered patients following an acute relapse [24][25][26].…”

“…A single study [27] found the opposite: significantly lower mean tNOx in RRMS patients compared to control groups; no significant study characteristics were identified to explain this disparity. tNOx has been considered across RRMS and SPMS groups with mixed resultsone study reported significantly higher mean tNOx in RRMS than SPMS [22] whereas others reported no significant difference [16,17,23].…”