Immune System Fingerprint in POTS found (proconvertase furin)

[Belbyr]

https://www.frontiersin.org/article...WEQ4Ga11svDwipyTuBzQuVCxHKBhF00zUeVvCTY7usHos

In this study, we explored the inflammatory proteomic signature of POTS in order to elucidate pathophysiological mechanisms underlying this particular phenotype of cardiovascular autonomic dysfunction. We demonstrated that POTS is associated with lower circulating levels of proprotein convertases subtilisin/kexin type (PCSK)-3, i.e., proconvertase furin. Interestingly, the earlier the disease starts, the lower the proconvertase furin level.
Our findings confirm and further expand the growing body of evidence pointing to an immune dysregulation as the primary pathophysiological mechanism underlying POTS. However, it is noteworthy that pro-inflammatory cytokines and chemokines, i.e., interleukin-7, interleukin-12 and CXC motif chemokine 13, associated with systemic inflammatory diseases such as systemic lupus erythromatosus or rheumatoid arthritis were not increased among POTS-positive patients.

Proteomic profiling by proximity extension technique revealed an inflammation-specific biomarker fingerprint in POTS patients. Circulating levels of proconvertase furin are downregulated in POTS suggesting a complex and intriguing interplay between autoimmune activity and cardiovascular autonomic dysfunction.

 

[andyguitar]

Thanks for posting that @Belbyr ,lots of auto-immune stuff coming up now. I expect we are getting nearer to the truth. About bleeding time!

 

[Belbyr]

Might as well pass this along since it (POTS) is so rampant in CFS.

@Ben H @Janet Dafoe (Rose49)

 

[Belbyr]

Missed this part on the side but this guy is probably top 3 researchers in the world on autonomic disorders, he signed off on it.

 

[andyguitar]

So gold plated research then. Nice one.

 

[Belbyr]

Some more clips after detail reading it several times:

In experimental models of rheumatoid arthritis, exogenous proconvertase furin has been successfully used to harness autoimmunity (Lin et al., 2012). This is consistent also with recent findings reporting the association between high proconvertase furin levels and lower systemic activity disease in primary Sjögren’s syndrome (Ranta et al., 2018).

While the exact source of circulating levels of this protein in POTS patients remains unclear, we speculate that they may reflect a so far undetected viral activity. Indeed, cleavage of the human papilloma virus capsid protein L2 by proconvertase furin is necessary for infection (Richards et al., 2006), while the HIV-1 protein Nef is known to bind furin in order to sequester human leukocyte antigen-family receptors in the trans-Golgi network (Piguet et al., 2000). Presumably as a countermeasure, proconvertase furin is down-regulated during inflammation in a suppressor of cytokine signaling (Sox)-dependent manner (Guimont et al., 2007).

 

[hixxy]

I wonder if this is unique to POTS or if it will turn out to also be meaningful to people with ME but no POTS.

 

[Mel9]

So low serum furin might be another marker for POTS?

 

[Belbyr]

So low serum furin might be another marker for POTS?

It looks like it has some potential, I think it would be a better one than the adrenergic antibodies which don't seem to capture all POTS patients like myself and some others on a facebook group I'm in.