Lymphopenia in multiple Sclerosis patients treated with dimethyl fumarate: the role of IL-2 in proliferative response of lymphocytes

• Grant number: 20/03558-6
• Support type: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): July 01, 2020
• Effective date (End): June 30, 2021
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal researcher: Leonilda Maria Barbosa dos Santos
• Grantee: Rodrigo Miranda de Carvalho
• Home Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 14/26431-0 - Multiple sclerosis, clinical study, neuropsychological, immunological, biomarkers and modifying-disease new drugs, AP.TEM

Abstract

A significant advance in the treatment of multiple sclerosis (MS) has marked the last two decades. The arrival of chimeric, humanized and currently fully human monoclonal antibodies has contributed to the attempt to decrease the progress of MS. However, due to a number of problems, not all patients adhere to injectable or infusible treatments. Therefore, in recent years there has been an investment in the treatment of MS orally. Dimethyl fumarate (Tecfidera) is an oral drug, approved for the treatment of the relapsing/remitting form of MS, used as a first-line treatment in several countries, and which is being introduced in Brazil. In addition to the beneficial effects described by treatment with DMF, some adverse effects such as gastrointestinal disorder and lymphopenia have also been observed. Lymphopenia is an important aspect, since infection with the JC virus has been described for patients with MS who had this side effect. Some mechanisms may explain lymphopenia after treatment with DMF, such as induction of lymphocyte apoptosis and defect in the proliferative response of these cells. Interleukin 2 (IL-2), among other functions, is important in the proliferative response of lymphocytes. Deficient production of this cytokine or IL-2 receptor expression may explain, at least in part, the reduced proliferative response of lymphocytes. In this study, we aim to study whether the lymphopenia observed in some patients after treatment with DMF is due to the deficient function of IL-2.