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

• Published in: Proceedings of the National Academy of Sciences - PNAS 2021-07, Vol.118 (28), p.1-7
• Main Authors: Huhn, Konstantin, Linz, Peter, Pemsel, Franziska, Michalke, Bernhard, Seyferth, Stefan, Kopp, Christoph, Chaudri, Mohammad Anwar, Rothhammer, Veit, Dörfler, Arnd, Uder, Michael, Nagel, Armin M., Müller, Dominik N., Waschbisch, Anne, Lee, De-Hyung, Bäuerle, Tobias, Linker, Ralf A., Haase, Stefanie
• Format: Article
• Language: English
• Subjects: Adult; Animal models; Animals; Biological Sciences; Chemical analysis; Disease Models, Animal; Experimental allergic encephalomyelitis; Humans; Immune system; Immunization; Inductively coupled plasma mass spectrometry; Inflammation; Inflammation - pathology; Magnetic Resonance Imaging; Male; Males; Mass spectrometry; Mass spectroscopy; Mice; Mice, Inbred C57BL; Multiple sclerosis; Multiple Sclerosis - diagnostic imaging; Multiple Sclerosis - metabolism; Multiple Sclerosis, Relapsing-Remitting - metabolism; Muscles; Patients; Signal Processing, Computer-Assisted; Skin - diagnostic imaging; Skin - metabolism; Sodium; Sodium - metabolism
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.2102549118

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.