From treatment to pathology: unravelling the effect of B cell depletion therapy and the role of IgD-CD27- double negative B cells in multiple sclerosis

Abstract

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS), characterized by demyelination, axonal degeneration and gliosis. MS is one of the most common non-traumatic neurological disorders in young adults, with symptoms typically appearing between the ages of 20 and 50 (1, 2). The mean age of diagnosis is 32 years, and MS is at least two times more common in females than in males. Currently, approximately 2.9 million people are living with MS worldwide, with Europe and North America showing the highest prevalence (2). Peripheral autoreactive immune cells infiltrate the CNS and damage the myelin sheet, axons and neurons. Consequently, demyelinating areas or lesions are formed and can be located around postcapillary venules in the white and grey matter of the brain, in the optic nerve and in the spinal cord (3). The resulting neuroinflammation and neurodegeneration lead to a disrupted conduction of electrical signals from the nerves to the periphery, causing a wide range of clinical symptoms. These clinical symptoms depend on the neuroanatomical region that is affected but mostly include fatigue, blurred vision, muscle weakness, muscle spasms, sensory loss, bowel and bladder dysfunction and cognitive disturbances (such as memory loss) (4, 5). While the clinical symptoms can vary widely among MS patients, they will eventually result in a sedentary lifestyle and adversely affect the quality of life. In addition, MS can directly or indirectly cause comorbidities, including depression, anxiety, arterial hypertension, diabetes mellitus and chronic lung disease (5-7). Both MS and its comorbidities place a burden on patients and the society due to the high healthcare costs and unemployment rates (8, 9).