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Post-exertional malaise
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==== Complement C4a ==== In 2003 Sorensen et al. found that the [[Complement C4a|complement split product C4a]] was increased after exercise in the 20 ME/CFS patients, but not in controls. Furthermore a significant correlation was found between the increase in C4a and total symptom score.<ref>{{Cite journal | last = Sorensen | first=Bristol | last2 = Streib | first2 = Joanne E. | last3 = Strand | first3 = Matthew | last4 = Make | first4 = Barry | last5 = Giclas | first5 = Patricia C. | last6 = Fleshner | first6 = Monika | last7 = Jones | first7 = James F. | date = Aug 2003 | title = Complement activation in a model of chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/12897748|journal=The Journal of Allergy and Clinical Immunology|volume=112|issue=2|pages=397–403|issn=0091-6749|pmid=12897748}}</ref> C4a is generated from the cleavage of the native complement protein C4 via the classical and lectin pathways. A follow up study, published in 2009, found that other elements of the lectin pathway also responded differently to an exercise challenge in ME/CFS patients compared to controls. Both C4 and mannan-binding lectin serine protease 2 (MASP2) were observed at higher levels in ME/CFS subjects 1 hour post-exercise.<ref>{{Cite journal | last = Sorensen | first=Bristol | author-link = | last2 = Jones | first2 = James F | authorlink2 = | last3 = Vernon | first3 = Suzanne D | authorlink3 = Suzanne Vernon | last4 = Rajeevan | first4 = Mangalathu S | authorlink4 = Mangalathu Rajeevan | author-link5 = | date = Jan 2009 | title = Transcriptional Control of Complement Activation in an Exercise Model of Chronic Fatigue Syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2583111/|journal=Molecular Medicine|volume=15|issue=1-2|pages=34–42|doi=10.2119/molmed.2008.00098|pmc=2583111|pmid=19015737|quote=|via=}}</ref> The authors speculated this to contribute to the increased C4a split product 6 hours after the exercise challenge. In a 2010 study by Nijs et al. there was no increase in C4a after exercise in ME/CFS patients, though a significant correlation with post-exertional pain and fatigue was found.<ref>{{Cite journal | last = Nijs | first = J. | last2 = Van Oosterwijck | first2 = J. | last3 = Meeus | first3 = M. | last4 = Lambrecht | first4 = L. | last5 = Metzger | first5 = K. | last6 = Frémont | first6 = M. | last7 = Paul | first7 = L. | date = Apr 2010 | title = Unravelling the nature of postexertional malaise in myalgic encephalomyelitis/chronic fatigue syndrome: the role of elastase, complement C4a and interleukin-1β|url=https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1365-2796.2009.02178.x|journal=Journal of Internal Medicine|volume=267|issue=4 | pages = 418–435|doi=10.1111/j.1365-2796.2009.02178.x|issn=0954-6820}}</ref>
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