TY - JOUR
T1 - Activating autoantibodies against G protein-coupled receptors in narcolepsy type 1
AU - Orjatsalo, Maija
AU - Partinen, Eemil
AU - Wallukat, Gerd
AU - Alakuijala, Anniina
AU - Partinen, Markku
PY - 2021/1
Y1 - 2021/1
N2 - Study objectives: Narcolepsy type 1 is a rare hypersomnia of central origin, which is caused by loss of hypothalamic neurons that produce the neuropeptides hypocretin-1 and -2. Hypocretin-containing nerve terminals are found in areas known to play a central role in autonomic control and in pain signaling. Cholinergic M2 receptors are found in brain areas involved with the occurrence of hallucinations and cataplexy. In addition to classical symptoms of narcolepsy, the patients suffer frequently from autonomic dysfunction, chronic pain, and hypnagogic/hypnopompic hallucinations. We aimed to test whether narcolepsy type 1 patients have autoantibodies against autonomic beta 2 adrenergic receptor, M2 muscarinic receptors, or nociception receptors.Methods: We tested the serum of ten narcolepsy type 1 patients (five female) for activating beta 2 adrenergic receptor autoantibodies, M2 muscarinic receptor autoantibodies, and nociception receptor autoantibodies.Results: Ten of ten patients were positive for muscarinic M2 receptor autoantibodies (P <0.001), 9/10 were positive for autoantibodies against nociception receptors (P <0.001), and 5/10 were positive for beta 2 adrenergic receptor autoantibodies (P <0.001).Conclusions: Narcolepsy type 1 patients harbored activating autoantibodies against M2 muscarinic receptors, nociception receptors, and beta 2 adrenergic receptors. M2 receptor autoantibodies may be related to the occurrence of cataplexy and, moreover, hallucinations in narcolepsy since they are found in the same brain areas that are involved with these symptoms. The occurrence of nociception receptor autoantibodies strengthens the association between narcolepsy type 1 and pain. The connection between narcolepsy type 1, autonomic complaints, and the presumed cardiovascular morbidity might be associated with the occurrence of beta 2 adrenergic receptor autoantibodies. On the other hand, the presence of the autoantibodies may be secondary to the destruction of the hypocretin pathways. (C) 2020 Elsevier B.V. All rights reserved.
AB - Study objectives: Narcolepsy type 1 is a rare hypersomnia of central origin, which is caused by loss of hypothalamic neurons that produce the neuropeptides hypocretin-1 and -2. Hypocretin-containing nerve terminals are found in areas known to play a central role in autonomic control and in pain signaling. Cholinergic M2 receptors are found in brain areas involved with the occurrence of hallucinations and cataplexy. In addition to classical symptoms of narcolepsy, the patients suffer frequently from autonomic dysfunction, chronic pain, and hypnagogic/hypnopompic hallucinations. We aimed to test whether narcolepsy type 1 patients have autoantibodies against autonomic beta 2 adrenergic receptor, M2 muscarinic receptors, or nociception receptors.Methods: We tested the serum of ten narcolepsy type 1 patients (five female) for activating beta 2 adrenergic receptor autoantibodies, M2 muscarinic receptor autoantibodies, and nociception receptor autoantibodies.Results: Ten of ten patients were positive for muscarinic M2 receptor autoantibodies (P <0.001), 9/10 were positive for autoantibodies against nociception receptors (P <0.001), and 5/10 were positive for beta 2 adrenergic receptor autoantibodies (P <0.001).Conclusions: Narcolepsy type 1 patients harbored activating autoantibodies against M2 muscarinic receptors, nociception receptors, and beta 2 adrenergic receptors. M2 receptor autoantibodies may be related to the occurrence of cataplexy and, moreover, hallucinations in narcolepsy since they are found in the same brain areas that are involved with these symptoms. The occurrence of nociception receptor autoantibodies strengthens the association between narcolepsy type 1 and pain. The connection between narcolepsy type 1, autonomic complaints, and the presumed cardiovascular morbidity might be associated with the occurrence of beta 2 adrenergic receptor autoantibodies. On the other hand, the presence of the autoantibodies may be secondary to the destruction of the hypocretin pathways. (C) 2020 Elsevier B.V. All rights reserved.
KW - AUTONOMIC CONTROL
KW - CARDIOMYOPATHY
KW - CATAPLEXY
KW - HEART-RATE-VARIABILITY
KW - Hypocretin
KW - M2 muscarinic receptor autoantibodies
KW - MUSCARINIC RECEPTORS
KW - Narcolepsy type 1
KW - Nociception receptor autoantibodies
KW - Orexin
KW - SCHIZOPHRENIA
KW - SLEEP
KW - STRIATUM
KW - beta 2 adrenergic receptor autoantibodies
KW - 3124 Neurology and psychiatry
U2 - 10.1016/j.sleep.2020.11.038
DO - 10.1016/j.sleep.2020.11.038
M3 - Article
SN - 1389-9457
VL - 77
SP - 82
EP - 87
JO - Sleep Medicine
JF - Sleep Medicine
ER -