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Trouble with tribbles: orexin, sleep and wakefulness, narcolepsy, autoantibodies

WillowJ

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http://www.medicalnewstoday.com/articles/290623.php

Following the [H1N1 flu] vaccination campaign [in Finland], the incidence of narcolepsy shot up to 16 times the average, says Prof. Shoenfeld.

The team had also become aware of a study reported by a group of sleep researchers in Japan who had discovered antibodies in the brain that appear to attack "tribbles" - small granules that contain brain cells that produce orexin, a brain chemical that helps maintain the delicate balance between sleep and wakefulness.

Prof. Shoenfeld says they have noticed how patients and animals with narcolepsy have less orexin in the brain, resulting in an imbalance between sleep and wakefulness, which leads to attacks of narcolepsy.

They think the antibodies are autoimmune.
 

WillowJ

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This might be the medical journal article:

http://www.journalsleep.org/ViewAbstract.aspx?pid=27838

Anti-Tribbles Homolog 2 (TRIB2) Autoantibodies in Narcolepsy are Associated with Recent Onset of Cataplexy
Minae Kawashima, PhD1; Ling Lin, MD, PhD1; Susumu Tanaka, PhD2; Poul Jennum MD, Dr. Med. Sci.3; Stine Knudsen, MD, PhD3; Sona Nevsimalova, MD4; Giuseppe Plazzi, MD5; Emmanuel Mignot, MD, PhD1


1Center for Narcolepsy, Stanford University School of Medicine, Palo Alto, CA; 2The Sleep Disorders Research Project, Tokyo Institute of Psychiatry, Tokyo Metropolitan Organization for Medical Research, Tokyo, Japan; 3Danish Center for Sleep Medicine, University of Copenhagen, Glostrup Hospital, Glostrup, Denmark; 4Department of Neurology, Charles University in Prague, 1st Faculty of Medicine and General Teaching Hospital, Prague, Czech Republic; 5Sleep Disorders Center, Department of Neurological Sciences, University of Bologna, Bologna, Italy

Study Objective: Recent studies have found increased autoantibodies against Tribbles homolog 2 (anti-TRIB2) and anti-streptolysin O (ASO) in narcolepsy. In this study, we replicated this finding with a primary focus on recent onset cases.

Participants and Methods: Participants included (1) 90 cases with cataplexy, (2) 57 cases without cataplexy, and (3) 156 age-sex matched controls, including 73 human leukocyte antigen (HLA)-DQB1*0602 allele carriers. A radioligand binding assay was used to detect anti-TRIB2 antibodies.

Results: Anti-TRIB2 antibodies were prevalent in HLA-DQB1*0602 positive cases with cataplexy (25.0% of 76) and rare in cases without cataplexy (3.5% of 57, OR = 9.2, 95% CI = 2.5 - 33.5, P = 6.0 x 10-4) or controls (4.5% of 156, OR = 7.1, 95% CI = 3.1 - 16.2, P = 9.3 x 10-6).

Anti-TRIB2 positivity in controls was not associated with DQB1*0602.

In DQB1*0602 narcolepsy-cataplexy cases, the presence of anti-TRIB2 was associated with short disease duration (2.3 years from cataplexy onset), with 41.0% positive in this group (OR = 7.4 versus cases with onset > 2.3 years, 95% CI = 1.9 - 28.5, P = 9.0 x 10-4).

Anti-TRIB2 positivity in 39 DQB1*0602 positive recent onset cases was associated with increased ASO antibody (> 200 IU) (OR = 6.2, 95% CI = 1.6 - 24.6, P = 0.01), but did not correlate with age, gender, or body mass index.

Conclusion: Anti-TRIB2 autoantibodies are strongly associated with narcolepsy close to cataplexy onset (≤ 2.3 years). Anti-TRIB2 was rarely found in cases without cataplexy or with distant onset.

Keywords: Human narcolepsy, Tribbles homolog 2 (TRIB2), autoantibody, anti-streptolysin O (ASO)

The full text appears to be free, but I cannot read it just now.

It relates to us because it's said that many PWME and PWfibro have narcolepsy.

It's also said that we have sleep wave intrusions during wake times, and wakeful wave intrusions during sleep. So maybe this sort of thing is going on?
 

WillowJ

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I actually found the study the article was referring to and it's a different one. Which is actually cool. Here's that:

http://www.sciencedirect.com/science/article/pii/S1043661814001662


Is narcolepsy a classical autoimmune disease?
  • a Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, Affiliated to Sackler Faculty of Medicine, Tel Aviv University, Israel
  • b Center for Autoimmune Diseases Research – CREA, Universidad del Rosario, Bogota, Colombia
  • c Doctoral Program in Biomedical Sciences, Universidad del Rosario, Bogota, Colombia
  • d Rheumatic Disease Unit, Sheba Medical Center, Tel-Hashomer, Israel
  • e The Dr. Pinchas Borenstein Talpiot Medical Leadership Program 2013, Sheba Medical Center, Tel-Hashomer, Israel
  • f Sackler Faculty of Medicine, Tel-Aviv University, Israel
  • g Incumbent of the Laura Schwarz-Kip Chair for Research of Autoimmune Diseases, Tel Aviv University, Israel

Abstract
Narcolepsy is a neurological disorder characterized by excessive daytime sleepiness. It is caused by the loss of orexin producing neurons in the lateral hypothalamus.

Current evidences suggest an autoimmune mediated process causing the specific loss of orexin neurons.

The high association of the disease with the HLA DQB1*06:02, as well as the link with environmental factors and are important clues supporting this theory.

Recently, the association between the occurrence of the disease and vaccination campaign after the 2009 H1N1 pandemic highlighted the importance to increase the knowledge in the Pandora box of the vaccines.

This review discusses the last finding regarding the pathogenesis of the disease and its relationship with the H1N1 vaccines.

Abbreviations
  • ASIA, autoimmune/autoinflammatory syndrome induced by adjuvants;
  • REM, rapid eye movement;
  • ICSD-3, International Classification of Sleep Disorders version 3;
  • MSLT, Multiple Sleep Latency Test;
  • CSF, cerebrospinal fluid;
  • Trib2, tribbles homolog 2 protein;
  • NEI, neuropeptide glutamic acid-isoleucine;
  • αMSH, α-melanocyte-stimulating hormone;
  • MCH, melanin-concentrating hormone neurons;
  • SGA, streptococcal group A;
  • HLA, human leukocyte antigen;
  • PANDAS, pediatric autoimmune disorders associated with streptococcal infections;
  • SOREMPs, sleep onset REM periods
Keywords
  • Narcolepsy;
  • Autoimmune diseases;
  • ASIA syndrome;
  • Adjuvant;
  • Infections;
  • H1N1

This one costs $35.95
 

alex3619

Senior Member
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Logan, Queensland, Australia
I have something resembling narcolepsy from time to time. I can stay awake but the concentration of doing that means I am incapacitated. I cannot even read or watch a movie. So the only thing to do is go to bed. Its not like narcolepsy in movies, I don't just nod off, but there is serious compulsion to sleep.

There is more to this than just orexin. I am not sure there is only one type of narcolepsy.
 

August59

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Every neurologist and sleep specialist I've seen considers narcolepsy to be an autoimmune disease.

Antibodies destroy hypocretins (orexin??). If cataplexy accompanies the narcolepsy then there is high probability that HLA variant is present.

http://med.stanford.edu/news/all-ne...immune-disorder-stanford-researcher-says.html

I'm like Alex as I can have episodes of moderate to severe narcolepsy, then go 6 months without any problems at all. I just happen to be in an episode when i had the MSLT (nap test). On one "nap" I had sleep latency of 9 seconds and was in REM stage in 45 seconds.

Over the last 6 months I can't fall asleep if I'm outside of my circadian rhythm which has my sleep period from 5am till 10am. From 10am till 1pm I'm in a can't sleep, but can't wake up stage. This pretty much falls directly i line with my cortisol levels by way of 4x saliva test (on 2 separate occasions.)
 

WillowJ

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I have something resembling narcolepsy from time to time. I can stay awake but the concentration of doing that means I am incapacitated. I cannot even read or watch a movie. So the only thing to do is go to bed. Its not like narcolepsy in movies, I don't just nod off, but there is serious compulsion to sleep.

There is more to this than just orexin. I am not sure there is only one type of narcolepsy.

I have similar symptoms from time to time.

It looked like the Kawashima paper noted the existence of subgroups, but I was not able to properly read it.
 

WillowJ

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Interestingly enough, the Stanford group also found an association with some biomarker and recent onset:

In DQB1*0602 narcolepsy-cataplexy cases, the presence of anti-TRIB2 was associated with short disease duration
 

August59

Daughters High School Graduation
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Upstate SC, USA