Narcolepsy type 1: what have we learned from immunology?

Author:

Kornum Birgitte R1

Affiliation:

1. Department of Neuroscience, University of Copenhagen, Copenhagen, Denmark

Abstract

Abstract Narcolepsy type 1 is hypothesized to be an autoimmune disease targeting the hypocretin/orexin neurons in the hypothalamus. Ample genetic and epidemiological evidence points in the direction of a pathogenesis involving the immune system, but this is not considered proof of autoimmunity. In fact, it remains a matter of debate how to prove that a given disease is indeed an autoimmune disease. In this review, a set of commonly used criteria for autoimmunity is described and applied to narcolepsy type 1. In favor of the autoimmune hypothesis are data showing that in narcolepsy type 1 a specific adaptive immune response is directed to hypocretin/orexin neurons. Autoreactive T cells and autoantibodies have been detected in blood samples from patients, but it remains to be seen if these T cells or antibodies are in fact present in the hypothalamus. It is also unclear if the autoreactive T cells and/or autoantibodies can transfer the disease to healthy individuals or animals or if immunization with the proposed autoantigens can induce the disease in animal models. Most importantly, it is still controversial whether suppression of the autoimmune response can prevent disease progression. In conclusion, narcolepsy type 1 does still not fully meet the criteria for being classified as a genuine autoimmune disease, but more and more results are pointing in that direction.

Publisher

Oxford University Press (OUP)

Subject

Physiology (medical),Neurology (clinical)

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