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Heat shock proteins and chronic fatigue in primary Sjögren's syndrome.

MikeJackmin

Senior Member
Messages
132
Innate Immun. 2016 Feb 25. pii: 1753425916633236. [Epub ahead of print]
Bårdsen K1, Nilsen MM2, Kvaløy JT3, Norheim KB4, Jonsson G5, Omdal R6.

Abstract
Fatigue occurs frequently in patients with cancer, neurological diseases and chronic inflammatory diseases, but the biological mechanisms that lead to and regulate fatigue are largely unknown. When the innate immune system is activated, heat shock proteins (HSPs) are produced to protect cells. Some extracellular HSPs appear to recognize cellular targets in the brain, and we hypothesize that fatigue may be generated by specific HSPs signalling through neuronal or glial cells in the central nervous system. From a cohort of patients with primary Sjögren's syndrome, 20 patients with high and 20 patients with low fatigue were selected. Fatigue was evaluated with a fatigue visual analogue scale. Plasma concentrations of HSP32, HSP60, HSP72 and HSP90α were measured and analysed to determine if there were associations with the level of fatigue. Plasma concentrations of HSP90α were significantly higher in patients with high fatigue compared with those with low fatigue, and there was a tendency to higher concentrations of HSP72 in patients with high fatigue compared with patients with low fatigue. There were no differences in concentrations of HSP32 and HSP60 between the high- and low-fatigue groups. Thus, extracellular HSPs, particularly HSP90α, may signal fatigue in chronic inflammation. This supports the hypothesis that fatigue is generated by cellular defence mechanisms.

http://www.ncbi.nlm.nih.gov/pubmed/26921255
 

Marco

Grrrrrrr!
Messages
2,386
Location
Near Cognac, France
Interesting but somewhat unexpected as several studies have found reduced HSP levels in PWME following exercise.

ETA - I do like the idea though that HSPs are another physiological signal that is recognised by glial cells.
 
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Snow Leopard

Hibernating
Messages
5,902
Location
South Australia
The comparison between "high fatigue" and "low fatigue" patients is interesting, but I fear self-report questionnaires are not valid to judge this - I would rather divide patient groups based on actigraphy.

There was this hypothesis paper a few years ago:

"HSP70 expression: does it a novel fatigue signalling factor from immune system to the brain?"

http://www.ufrgs.br/fisiologiacelular/site/arqs/ENSINO/artigos em PDF/HSP70 expression - does it a novel fatigue signalling factor from immune system to the brain.pdf

HSP are unlikely to be the cellular signal for fatigue, yet they are obviously associated with cellular stress responses, some of which may indeed be involved with fatigue.

There have been three studies in CFS patients, all of which showed impaired HSP gene expression or levels of certain HSP after exercise.

http://www.ncbi.nlm.nih.gov/pubmed/19032901
http://www.ncbi.nlm.nih.gov/pubmed/19457057
http://www.ncbi.nlm.nih.gov/pubmed/22112145

Yves Jammes suggests the following hypothesis.
The lack of HSP response explains why CFS patients present an exacerbated ROS production after cycling exercise (please see {2} in which I am listed as an author), which might explain their altered muscle function. Because in a majority of CFS patients chronic muscle fatigue occurs after a prolonged period of physical hyperactivity, this raises the question of a reduced expression of HSP inductors after repetitive stimulation and thus of possible deleterious effects of repetitive strenuous exercise bouts.
http://f1000.com/prime/1162481

Related previous discussion:
http://forums.phoenixrising.me/inde...-impaired-response-to-oxidative-stress.15018/

There is also this study, but I don't know what to make of it:
"Epitopes of Microbial and Human Heat Shock Protein 60 and Their Recognition in Myalgic Encephalomyelitis"
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0081155

And before anyone gets too excited, there are training effects that can increase HSP expression, so....
http://www.ncbi.nlm.nih.gov/pubmed/15459833

This is an interesting study too (from Alan Light and colleagues)
Fatigue sensation and gene expression in trained cyclists following a 40 km time trial in the heat
http://link.springer.com/article/10.1007/s00421-015-3311-9
 
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