Skin sodium is increased in male patients with multiple sclerosis and related animal models

Abstract

Significance Our data add to the recently identified importance of the skin as a storage compartment of sodium. We found a higher sodium MRI (23Na-MRI) signal in the skin of male multiple sclerosis (MS) patients compared to matched healthy controls as well as in the animal model, experimental autoimmune encephalomyelitis. Considering the salt effects on macrophage and T-cell immunology during MS and the persisting challenge to accurately determine the actual sodium load via salt excretion, the noninvasive determination of sodium by 23Na-MRI analysis of the skin may represent an important method for further investigations on sodium and MS risk. Novel MRI techniques allow a noninvasive quantification of tissue sodium and reveal the skin as a prominent compartment of sodium storage in health and disease. Since multiple sclerosis (MS) immunopathology is initiated in the periphery and increased sodium concentrations induce proinflammatory immune cells, the skin represents a promising compartment linking high sodium concentrations and MS immunopathology. We used a 7-T sodium MRI (23Na-MRI) and inductively coupled plasma mass spectrometry to investigate the skin sodium content in two mouse models of MS. We additionally performed 3-T 23Na-MRI of calf skin and muscles in 29 male relapsing-remitting MS (RRMS) patients and 29 matched healthy controls. Demographic and clinical information was collected from interviews, and disease activity was assessed by expanded disability status scale scoring. 23Na-MRI and chemical analysis demonstrated a significantly increased sodium content in the skin during experimental autoimmune encephalomyelitis independent of active immunization. In male patients with RRMS, 23Na-MRI demonstrated a higher sodium signal in the area of the skin compared to age- and biological sex-matched healthy controls with higher sodium, predicting future disease activity in cranial MRI. In both studies, the sodium enrichment was specific to the skin, as we found no alterations of sodium signals in the muscle or other tissues. Our data add to the recently identified importance of the skin as a storage compartment of sodium and may further represent an important organ for future investigations on salt as a proinflammatory agent driving autoimmune neuroinflammation such as that in MS.