I understand the point you have made previously about inflammation being a specific thing with heat and swelling and white blood cells, and that not seeming to be part of ME/CFS. And about the importance of being specific about what is meant when inflammation is mentioned.2. The study is yet another powerful indicator that there is no inflammation or damage going on.
But, I'm not sure what you are seeing in this particular paper that supports the absence of inflammation. The authors seem quite convinced that they are in fact seeing evidence for inflammation. Perhaps it is just that different idea about what inflammation is?
Searching on 'inflammation' in the paper produces content like these quotes:
Conclusion - Our findings characterize a pathophysiology in ME/CFS composed of interrelated elements, including immune dysregulation, vascular dysfunction, metabolic stress, and chronic inflammation. The observed multiscale patterns of change converge on a mechanism involving coordinated immune, vascular, and metabolic disturbances.
In summary, the pattern of elevated secretory activity in the ME/CFS group is mechanistically consistent with immune dysregulation, inflammatory responses, and metabolic stress.
This clearly showed a skewed pattern of increase for affected secretome proteins involved in coagulation, complement pathways, and inflammation (chemokines, interleukins).
Immune dysregulation, as reported in multiple studies 15,16,55, may be mechanistically associated with an underlying autoimmune pathomechanism, the overall state of elevated secretory activity, and increased levels of factors involved in inflammation, coagulation, and complement activity. Similar observations have previously been highlighted in relation to ME/CFS and long COVID
For the next two quotes, I'm not really sure if they are saying the proteins increase or decrease inflammation:
To specifically address aspects of immune dysregulation, we used annotated protein panels (HPA) specific to B-cells, T-cells, NK-cells, dendritic cells, monocytes, and granulocytes (Figure 4D). The effects associated with these cell types pointed to possible impacts on immune cell interactions, coagulation, and inflammation. As previously mentioned, multiple proteins associated with granulocytes showed significantly lower levels in the ME/CFS group compared to the HC group, such as MPO and BPI. The reduced amount of granulocyte proteins was not associated with abnormally low neutrophil counts (the most abundant type of granulocytes) or other leukocyte types in the patients (DocumentS1, Table S1). Furthermore, comparing a list of proteins associated with neutrophil granules and stimulated neutrophil protein release 33 45, we found that about 40% or more of the proteins reported to be released by activated neutrophils showed lower serum concentrations in the ME/CFS group compared to the HC group, suggesting a suppressive effect on overall neutrophil activity.
We performed a ligand-receptor interaction analysis to elucidate possible patterns of regulation that could be related to the pathomechanism of ME/CFS (DocumentS1, Figure S1). Overall, we found an overweight of cell adhesion and cytokine-cytokine receptor type ligand-receptor interactions. Interestingly, four members of the Ephrin subfamily A receptors (EPHA) and their ligands (EFNA) displayed concordance, supporting the involvement of altered EPHA-EFNA signaling in ME/CFS, as previously suggested 29. Furthermore, there was a positive concordance between Fibroblast growth factor receptor 3 (FGFR3) and EPHA, IL6R with the CNTF and MPZ ligands, and FLRT3 with UNC5B and UNC5D. FAP and PAM had negative concordance, along with other interactions. Based on current knowledge, it seems likely that the identified ligand-receptor interactions may play a role in ME/CFS pathology through their impact on metabolic regulation, tissue development and repair, inflammation, and angiogenesis.