Chronic fatigue syndrome and complement activation, 2009, Geller, Giclas

[Hutan]

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3028106/
Chronic fatigue syndrome and complement activation
Robert Dennis Geller; Patricia C Giclas

Abstract

This report describes a case of chronic fatigue syndrome (CFS) that followed a well-documented episode of acute Epstein–Barr virus (EBV) mononucleosis. All aetiological tests for chronic fatigue were found to be negative or normal, as were immunological tests.

After 2 years of chronic fatigue following the acute illness, measurements of complement split products were performed to test for complement activation. These were positive and remained positive for 14 months, after which the patient then recovered from CFS.

 

[Hutan]

In May 1991, to further investigate immune activity, plasma was analysed at the National Jewish Medical and Research Center to determine whether evidence of complement activation could be detected. Since the activation of complement gives rise to split products, these were measured in her plasma. Samples of plasma were obtained in the resting state, generally in the morning soon after awakening. Elevated levels were initially found for C4a and SC5b-9. Further analyses were performed over the following 14 months and the results are shown in table 1. The patient had elevated levels of complement split products from May 1991 through to March 1992. Levels of C4a were elevated on each determination, but other split products were also elevated. In July 1992, all of the complement split products results became normal for the first time.

While the levels of complement split products were elevated, the patient remained chronically and severely fatigued with the symptoms described above. Notably, within 2 months of normalisation of split products levels, the patient had complete resolution of all symptoms of CFS and returned to work. The patient continues to be followed and has remained well to the present, being free of any symptoms of CFS for 16 years.

In 2003, B Sorensen and co-workers reported elevation of baseline complement split product C4a, but not C3a or C5a, in patients with CFS following exercise.1 Our patient had an established diagnosis of post EBV CFS, and after considerable negative laboratory testing was found to have activation of complement as determined by elevated levels of measured complement split products. To our knowledge, this is the first time that this determination was ever made. Moreover, these elevations were from samples taken at rest, whereas in the model of Sorensen and co-workers1 the elevated levels were after exercise.

 

[Hutan]

There has been a recent report of elevated complement product levels in Covid-19:

sC5b9 plasma levels are elevated in children with SARS-CoV-2 infection, even if they have minimal symptoms of COVID-19.

Maybe that's not so remarkable, as it sounds as though complement activation fragments are markers for ongoing immune reactions.

complement activation fragments C4a, Bb, C3a, iC3b, C5a and SC5b-9 can be useful markers for ongoing immune reactions of various types. Because each of these fragments is associated with a known pathway, or pathways, of complement activation, looking at the pattern of activation fragments in a blood specimen at a given point of time can offer clues as to what may be going on in vivo. In CFS, the underlying mechanism of complement activation is usually unknown, but often levels of C3a and/or C4a are elevated as in the case presented here. The likely suspects are classical pathway activation through immune complexes (eg, viral capsid binding). Direct tests for immune complexes in the circulation are often negative, but the presence of the high levels of C3a and C4a in the patient’s circulation suggests an ongoing activation process.

 

[Snow Leopard]

I'm not convinced this finding is generalisable to all CFS or ME patients, it may simply suggest that there are a range of underlying conditions in people with CFS diagnoses. The authors do not discuss it, but I wonder if the patient was suffering from some form of vasculitis.

There does seem to be a strong association with SLE:
https://pubmed.ncbi.nlm.nih.gov/9777539/
https://academic.oup.com/rheumatology/article/44/10/1227/1788289


Further reading: https://en.wikipedia.org/wiki/Complement_membrane_attack_complex

 

[wastwater]

I’m pinning my hopes on immune Factor I inherited immunodeficiency being the root of my condition it is connected to the eye but is mentioned in other conditions like Autism schizophrenia Parkinson MS and Alzheimer’s
Maybe anti C5 will stop the complement activation that EBV started