Proteomics and cytokine analyses distinguish myalgic encephalomyelitis/chronic fatigue syndrome cases from controls, 2023, Giloteaux et al

[SNT Gatchaman]

@Hoopoe commented about this paper in a Covid-related thread. Noting that increased SERPINA5 levels positively correlated with higher SF-36 (ie better functioning / less disability) the authors had this comment in the discussion —

SERPINA5 is a secreted serine protease inhibitor whose functions are not completely understood. It was originally identified as an inhibitor of the anticoagulant protease-activated protein C. While this fact suggests that higher SERPINA5 might increase coagulation, an in vitro study demonstrated that SERPINA5 can serve as both an anti-coagulant and a pro-coagulant depending on the presence of thrombomodulin. Platelets contain SERPINA5 mRNA and can also take up the protein from the external milieu. Our finding of a correlation of ME/CFS health status with a protein involved in hemostasis may be relevant to the recent findings of activated platelets and microclots in ME/CFS, as well as altered platelet gene expression profiles. Furthermore, variants in the SERPINA5 gene have previously been associated with ME/CFS [70].

Ref 70 is Pathway-focused genetic evaluation of immune and inflammation related genes with chronic fatigue syndrome (2015, Human Immunology) which @dreampop noted up-thread in comment #14. I don't think we have a thread for that paper as it's from 2015, but it also used Fukudu/CDC 1994. It may be worth re-looking at it, given some of the coagulation pathologies more recently suggested in LC.

In brief though, that paper said —

rs6112 [C/T] in SERPINA5 was also associated with the number of CFS symptoms (p = 8.1 x 10-4 ).

Some of the microRNAs impacted by CFS associated SNPs include [...] and hsa-miR-1258 by rs9113 [C/T] in SERPINA5. A missense variant in SERPINA5 (rs6115 [A/G]) was also associated with CFS. Since these SERPINA5 variants are not in LD, they may confer independent risk for CFS. SERPINA5, an inhibitor of activated protein C, is located in chromosome 4

 

[Dolphin]

https://neuroimmune.cornell.edu/news/

New insights into ME/CFS using a multiomic approach


A new open access publication in the Journal of Translational Medicine describes the work by Giloteaux et al. to uncover ways to detect the disease ME/CFS. Ludovic Giloteaux and Jiayin Li, joint first authors, took a collaborative approach to improve our understanding of ME/CFS. Giloteaux isolated extracellular vesicles from the plasma of 98 Chronic Fatigue Initiative individuals (49 ME/CFS and 49 controls) to study their signaling molecules (i.e., cytokines). Then he worked with Jiayin Li and David Ruppert, statisticians at Cornell, and using data generated by Columbia University investigators, the group combined plasma cytokine, EV cytokine, plasma proteomic, and demographic datasets to explore new ways to approach ME/CFS.

Ludovic Giloteaux
One of the key findings from the publication is the 86% accuracy in differentiating between people with ME/CFS and health controls. Giloteaux et al. leveraged multiple datasets to achieve this goal. The paper also outlines interesting correlations between various biological molecules and clinical surveys that measure disease severity. For example, higher levels of pro-inflammatory molecules (e.g., CSF2 & TNFa) were correlated with greater physical and fatigue symptoms in people with ME/CFS.

The publication is open access so see the website for more information. Additionally, the EV cytokine data is available on mapMECFS.

By Ludovic Giloteaux