Complement Component C1q as a Potential Diagnostic Tool for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Subtyping, 2021, Castro-Marrero et al

There was a recent Austrian study (Lutz et al. 2021) that had a similar design (report the results of blood tests in a large group of ME/CFS patients but without a control group). It reported that:

"Reduced MBL (mannose-binding lectin) levels were found in 32% of ME/CFS patients, and MBL deficiency in 7%"
​

A quick search learned that Mannose binding lectin (MBL) "shares functional features in common with C1q".

Might there be a connection between the two?

 

Maybe it means that 9 drugs in the NSAIDs category were used, by 42.9% of patients, and so on.

 

This paper explains:

C4a is generated from the cleavage of the native complement protein C4 via the classical and lectin pathways. In the classical pathway, C4 is cleaved by C1s activated by C1q, whereas in the lectin pathway, C4 is cleaved by mannan-binding lectin serine protease 2 (MASP2), activated by mannose-binding lectins (MBL) or ficolins (FCN).​

 

I was thinking that a complement imbalance might make some sense for ME.

It ought to be too much complement to make it different from complement depletion as in lupus.

High C1q would be too much. Low MBP would allow C1q to build up. It would point to a problem with too much classical pathway activation maybe. MBP and alternative pathway do not use C1q.

Complement is interesting in that it sets things up for cascades of signalling. An imbalance could be a basis for a signalling dysregulation acquired in mid life rather than congenital. Lupus appears mostly in the 15-35 y age range.

Complement is also interesting in that it is involved in neural plasticity.

Of course a background complement imbalance ought to show up clearly on DecodeME, if the screening process tags the alleles effectively (the technical details are beyond me here).

 

What if the imbalance is not primarily genetic?

 

The only long term acquired imbalance I can think of would be due to an autoantibody to an inhibitor or complement clearance process. I would expect the effects of that to be both unstable and evident in some obvious change in levels - markedly low levels of some factor like CD55. Maybe not but it seems to me unlikely. Any antibody that binds to a complement factor of any sort would seem likely to lead to consumption since antibody binding activates.

A genetic imbalance seems more plausible in that it might be well hidden. C4 gene aberrations are thought to contribute to lupus despite C4 levels themselves being normal most of the time. A complement regulatory shift that was particularly relevant to CNS could be a possibility. Maybe complement is activated in some way in fever in the brain and that is not handled right.

 

This Belgian study reported changes in complement C4 after exercise in ME/CFS patients but not in healthy controls
Exercise-induce hyperalgesia, complement system and elastase activation in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - a secondary analysis of experimental comparative studies - PubMed (nih.gov)

 

This company’s focus includes C1q
https://annexonbio.com/pipeline/

 

https://www.akaritx.com/c5-complement-system/
powerful inflammatory substance that engages two cell surface G-protein coupled receptors, and into C5b

mode of action (I wonder how expensive it is )
https://www.akaritx.com/mode-of-action/

 

I created an Information Extraction system specifically for researching ME/CFS. It looks at 700+ medical concepts related either directly or indirectly to ME/CFS. Submitting the C1Q as query to the system, returns :

It is very interesting that the system returned concepts that are highly ranked related to mannose binding lectin as @Michiel Tack mentioned. I then submit to the same system "C1Q AND Mannose Binding lectin"

The results :

I find it interesting that other concepts we heard about such as thrombospondin, collagen are highly ranked. FWIW i have extremely high IgE levels (Hyper-IgE syndrome) which is considered a primary immunodeficiency (also in the results)

 

https://jneuroinflammation.biomedce...Nz9Zjjs4jcMG1pN4h7_iziLYP4LsgjyG8AZ4AVtNXtFas
Complement component C3a plays a critical role in endothelial activation and leukocyte recruitment into the brain

 

Study centre for complement

https://complement.org.uk/

complement deficiency

https://en.m.wikipedia.org/wiki/Complement_deficiency