Erythrocytes in multiple sclerosis - forgotten contributors to the pathophysiology?

Abstract

Multiple sclerosis (MS) is an autoimmune disease characterised by lymphocytic infiltration of the central nervous system and subsequent destruction of myelin and axons. On the background of a genetic predisposition to autoimmunity, environmental triggers are assumed to initiate the disease. The majority of MS research has focused on the pathological involvement of lymphocytes and other immune cells, yet a paucity of attention has been given to erythrocytes, which may play an important role in MS pathology. The following review briefly summarises how erythrocytes may contribute to MS pathology through impaired antioxidant capacity and altered haemorheological features. The effect of disease-modifying therapies on erythrocytes is also reviewed. It may be important to further investigate erythrocytes in MS, as this could broaden the understanding of the pathological mechanisms of the disease, as well as potentially lead to the discovery of novel and innovative targets for future therapies.

Keywords: Erythrocytes; antioxidant enzymes; haemorheology; multiple sclerosis.

Figure 1.

Erythrocyte antioxidant enzymes in multiple sclerosis. The figure shows (a) three of the erythrocyte antioxidant enzymes – superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase – and the reaction they catalyse to combat the effects of oxidative stress. Activities of erythrocyte SOD, GPx and catalase are altered in clinically isolated syndrome, relapsing–remitting MS, and secondary progressive MS compared to healthy controls. Nitric oxide synthase (NOS) catalyses the synthesis of nitric oxide, which may contribute to oxidative stress following the reaction with superoxide resulting in peroxynitrite. (b) Adrenocorticotropic hormone (ACTH) and (c) melatonin enhance and suppress various erythrocyte enzymes.