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The immune signatures of multiple sclerosis: Lessons from twin studies [Commentaries]
Proceedings of the National Academy of Sciences of the United States of America ( IF 9.412 ) Pub Date : 2020-09-14 , DOI: 10.1073/pnas.2016711117
Pablo Villoslada, Scott S. Zamvil

The advances of immunology in the last decades have been spectacular, both at the basic and the translational level. This progress has led to the discovery of many immunotherapies for autoimmune diseases and cancer. Besides, whole-genome sequencing studies have confirmed that the genetic susceptibility for autoimmune diseases such as multiple sclerosis (MS) is mainly driven by the HLA and other immune genes regulating the adaptive and innate immune response (1). However, the same level of advances has not materialized for understanding how autoimmune responses are generated and damage the central nervous system (CNS) in patients with MS (2). Decades of efforts searching for the antigen targeted in autoimmune CNS diseases have provided some successes, such as the identification of aquaporin-4 in the case of neuromyelitis optica (3) or myelin oligodendrocyte glycoprotein (MOG) in MOG antibody-associated encephalomyelitis (4). However, antigens responsible for the autoimmune response in MS have remained elusive (5, 6), even though new candidate antigens have been recently discovered (7, 8) which may involve cross-reactivity or epitope spreading processes (9). Identification of target antigens is critical for the development of antigen-specific tolerization as a path for restoring the homeostasis of the immune system and preventing tissue damage (10). Similarly, the search for the cells and molecules responsible for CNS damage in MS has been intensive. Still, it has failed to provide definite evidence for the involvement of one or several encephalitogenic immune cells that drives the autoimmune response against the CNS or orchestrates the chronic compartmentalized inflammation inside the CNS (11). However, the high efficacy of anti-CD20 therapies in MS has placed B cells in the spotlight (12).
更新日期:2020-09-15

 

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