{"id":938,"date":"2019-06-21T11:31:33","date_gmt":"2019-06-21T15:31:33","guid":{"rendered":"http:\/\/www.dysautonomiainternational.org\/blog\/wordpress\/?p=938"},"modified":"2019-06-24T09:31:45","modified_gmt":"2019-06-24T13:31:45","slug":"research-update-low-furin-levels-in-pots","status":"publish","type":"post","link":"https:\/\/dysautonomiainternational.org\/blog\/wordpress\/research-update-low-furin-levels-in-pots\/","title":{"rendered":"Research Update: Low Furin Levels in POTS"},"content":{"rendered":"

“If we want an answer from nature, we must put our questions in acts, not words, and the acts may take us to curious places. Some questions were answered in the laboratory, others in mines, others in a hospital where a surgeon pushed tubes in my arteries to get blood samples, others on top of Pike\u2019s Peak in the Rocky Mountains, or in a diving dress on the bottom of the sea. That is one of the things I like about scientific research. You never know where it will take you next.”\u00a0 \u2014 J.B.S. Haldane<\/em>
\n From essay ‘Some Adventures of a Biologist’, as quoted in Ruth Moore, Man, Time, And Fossils (1953), 174<\/em><\/p>\n

While not dressed as suggested by Dr. Haldane, I recently joined a massive expedition
\nintent on making new scientific discoveries. Working with an international group of
\ncolleagues, I screened blood samples from 113 Swedish individuals with POTS and 283
\npeople who don\u2019t have POTS (controls) in search of one or more biomarkers.
\nBiomarkers are molecules present in a biological sample at concentrations that are
\nclearly different between patients and healthy people. Ideally, a biomarker would also
\nbe more abnormal in more severe disease states, and closer to normal as a patient\u2019s
\nsymptoms improved or went in remission. In this particular case, we were hoping to
\nidentify a biomarker that is as reliable and specific as the tilt test for identifying POTS,
\nso that someday, perhaps, POTS can be diagnosed by a blood test rather than the tilt
\ntest. We used a new testing approach called Proximity Extension Assay, which allows
\nus to measure concentrations of 57 human protein biomarkers in a single sample
\nthanks to new DNA technology.<\/p>\n

So, did we catch anything? The answer is yes, although we are still trying to puzzle out
\nthe implications. We found one protein that was significantly less common in the blood
\nof POTS patients than in the blood of controls \u2013 furin. This protein was found in much
\nlower concentrations in POTS patients than in controls, but was also less abundant in
\nthe blood of POTS patients with more severe POTS on tilt testing than in those with
\nmilder POTS.<\/p>\n

\"Furin\"<\/a><\/p>\n

Furin promotes the maturation of secreted chemical messengers at the cell surface.
\nFurin is found throughout the body and has been reported to process a large number of
\ncytokines and chemokines, including anti-inflammatory transforming growth factor
\n(TGF)-\u03b21 and pro-inflammatory secreted TNF-family members. Cytokines and
\nchemokines play important roles in the immune system.<\/p>\n

Interestingly, previous evidence has suggested that inhibition of furin may result in a
\nbreakdown of peripheral immune tolerance (Pesu et al., 2008) and development of
\nsystemic autoimmune disease (Lisi et al., 2010). Recent findings report low furin levels
\ncorrelate to worsening systemic disease activity in Sj\u00f6gren\u2019s syndrome (Ranta et al.,
\n2018). It is important to note that only one POTS patient in our series had a confirmed
\nautoimmune disease, so there is much we still have to learn about the immune system
\nin POTS.<\/p>\n

So how does this help us diagnose and treat POTS? Well, if our findings are replicated
\nin other populations, a furin blood test may assist in diagnosing POTS in the future. It
\nmay also be that POTS patients with a very low furin may respond in a different way to
\ncertain treatments than do those with more normal levels of furin. There is much
\nresearch to be done exploring why POTS patients have low furin levels, and how this
\nimpacts their immune system.<\/p>\n

As said so well by Dr. Haldane, \u201cIf we want an answer from nature, we must put our
\nquestions in acts, not words\u2026\u201d! This is what I intend to do, continuing now from the
\nbottom of the sea to the next curious place. Stay tuned!<\/p>\n

\"Screen<\/a>Guest blogger Jonas Axelsson, MD, PhD is the Director of the Center for Apheresis and Stem Cell Handling and an Associate Professor of Renal Medicine at the Karolinska Institutet in Sweden. He is interested in studying the immune system in POTS, ME\/CFS and other conditions. He will be a guest speaker at the Dysautonomia International 7th Annual Conference this summer, where he will also be conducting a research study exploring even more immune and genetic biomarkers in POTS. When he\u2019s not trying to figure out complicated diseases in the lab, he enjoys sailing, diving and photography.<\/em><\/p>\n

REFERENCES<\/strong>
\nSpahic, J., Ricci, F., Aung, N., Axelsson, J., Melander, O., Sutton, R., Hamrefors, V., and Fedorowski, A. Proconvertase Furin Is Downregulated in Postural Orthostatic Tachycardia Syndrome. Front. Neurosci<\/em>., 29 March 2019. doi.org\/10.3389\/fnins.2019.00301
\nPubMed Abstract<\/a>\u00a0|\u00a0CrossRef Full Text<\/a>\u00a0|\u00a0Google Scholar<\/a><\/p>\n

Pesu, M., Watford, W. T., Wei, L., Xu, L., Fuss, I., Strober, W., et al. (2008). T-cell-expressed proprotein convertase furin is essential for maintenance of peripheral immune tolerance.\u00a0Nature<\/em>\u00a0455, 246\u2013250. doi: 10.1038\/nature07210
\nPubMed Abstract<\/a>\u00a0|\u00a0CrossRef Full Text<\/a>\u00a0|\u00a0Google Scholar<\/a><\/p>\n

Lisi, S., Sisto, M., Lofrumento, D. D., Cucci, L., Frassanito, M. A., Mitolo, V., et al. (2010). Pro-inflammatory role of Anti-Ro\/SSA autoantibodies through the activation of Furin-TACE-amphiregulin axis.\u00a0J. Autoimmun.<\/em>\u00a035, 160\u2013170. doi: 10.1016\/j.jaut.2010.06.020
\nPubMed Abstract<\/a>\u00a0|\u00a0CrossRef Full Text<\/a>\u00a0|\u00a0Google Scholar<\/a><\/p>\n

Ranta, N., Valli, A., Gronholm, A., Silvennoinen, O., Isomaki, P., Pesu, M., et al.\u00a0(2018). Proprotein convertase enzyme FURIN is upregulated in primary Sjogren\u2019s syndrome.Clin. Exp. Rheumatol.<\/em>\u00a036(Suppl. 112), 47\u201350.
\nGoogle Scholar<\/a><\/p>\n

Piguet, V., Wan, L., Borel, C., Mangasarian, A., Demaurex, N., Thomas, G., et al. (2000). HIV-1 Nef protein binds to the cellular protein PACS-1 to downregulate class I major histocompatibility complexes.\u00a0Nat. Cell. Biol.<\/em>\u00a02, 163\u2013167. doi: 10.1038\/35004038
\nPubMed Abstract<\/a>\u00a0|\u00a0CrossRef Full Text<\/a>\u00a0|\u00a0Google Scholar<\/a><\/p>\n

Guimont, P., Grondin, F., and Dubois, C. M. (2007). Sox9-dependent transcriptional regulation of the proprotein convertase furin.\u00a0Am. J. Physiol. Cell Physiol.<\/em>\u00a0293, C172\u2013C183. doi: 10.1152\/ajpcell.00349.2006
\nPubMed Abstract<\/a>\u00a0|\u00a0CrossRef Full Text<\/a>\u00a0|\u00a0Google Scholar<\/a><\/p>\n\"Facebook\"<\/a>\"twitter\"<\/a>\"linkedin\"<\/a>\"youtube\"<\/a>\"vimeo\"<\/a>\"instagram\"<\/a>\"mail\"<\/a>by <\/span>\"feather\"<\/a>\"Facebook\"<\/a>\"twitter\"<\/a>\"reddit\"<\/a>\"linkedin\"<\/a>\"tumblr\"<\/a>\"mail\"<\/a>by <\/span>\"feather\"<\/a>","protected":false},"excerpt":{"rendered":"

“If we want an answer from nature, we must put our questions in acts, not words, and the acts may take us to curious places. Some questions were answered in the laboratory, others in mines, others in a hospital where a surgeon pushed tubes in my arteries to get blood samples, others on top of … Continue reading Research Update: Low Furin Levels in POTS<\/span> →<\/span><\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[1],"tags":[],"class_list":["post-938","post","type-post","status-publish","format-standard","hentry","category-uncategorized"],"_links":{"self":[{"href":"https:\/\/dysautonomiainternational.org\/blog\/wordpress\/wp-json\/wp\/v2\/posts\/938","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/dysautonomiainternational.org\/blog\/wordpress\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/dysautonomiainternational.org\/blog\/wordpress\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/dysautonomiainternational.org\/blog\/wordpress\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/dysautonomiainternational.org\/blog\/wordpress\/wp-json\/wp\/v2\/comments?post=938"}],"version-history":[{"count":9,"href":"https:\/\/dysautonomiainternational.org\/blog\/wordpress\/wp-json\/wp\/v2\/posts\/938\/revisions"}],"predecessor-version":[{"id":952,"href":"https:\/\/dysautonomiainternational.org\/blog\/wordpress\/wp-json\/wp\/v2\/posts\/938\/revisions\/952"}],"wp:attachment":[{"href":"https:\/\/dysautonomiainternational.org\/blog\/wordpress\/wp-json\/wp\/v2\/media?parent=938"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/dysautonomiainternational.org\/blog\/wordpress\/wp-json\/wp\/v2\/categories?post=938"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/dysautonomiainternational.org\/blog\/wordpress\/wp-json\/wp\/v2\/tags?post=938"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}