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?
 
Michiel Tack said:
Looks like a useful paper with data from 250 women that meet Fukuda and Canadian criteria. The full dataset has been made available in the supplementary material. Patients must have been really ill with a mean score for SF-36 physical functioning of 26.9.
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I would expect people with severe and very severe ME to score 0 to10 on SF36 physical functioning, unless their severity is mostly severely disabling cognitive problems. To me a score around 25 would be moderate, and 35 to 50 mild. I can only base that on my own experience, but on that basis the mean given would indicate to me that patients were across the severity spectrum, averaging moderate.
 
Michiel Tack said:
Might there be a connection between the two?
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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).
 
Snow Leopard said:
What if the imbalance is not primarily genetic?
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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.
 
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 :


c1q.csv=0.6620196
complement_system.csv=0.6617494
igg.csv=0.660971
mannose.csv=0.6608677
lectin.csv=0.6607894
igm.csv=0.6607128
phagocytosis.csv=0.66064525
opsonins.csv=0.6606097
hyaluronan.csv=0.6603402
collagen.csv=0.6601587
iga.csv=0.6595076
adiponectin.csv=0.6593211
microglia.csv=0.6592876
human_proteinuria.csv=0.65904075
denaturation.csv=0.65806204
dendritic_cells.csv=0.6580235
cardiolipin.csv=0.6579109
amyloid.csv=0.65787876
immune_response.csv=0.65725297
hydroxyproline.csv=0.65711427
macrophage.csv=0.6566898
albumin.csv=0.65647256
cd14.csv=0.65613973
lipopolysaccharide.csv=0.65604216
glycoproteins.csv=0.65596914
rituximab.csv=0.65584445
hla.csv=0.65572596
mertk.csv=0.65555674
neuroinflammation.csv=0.6555334
proline_human.csv=0.6548993
hydroxylation.csv=0.6542876
mast_cells.csv=0.65344954
chondroitin_sulfate.csv=0.6532779
disulfide_bonds.csv=0.65309775
lysine_residues.csv=0.65295464
biotin.csv=0.65278596
mtdna.csv=0.6521859
glycosylation.csv=0.65191674
phenylalanine.csv=0.65157366
sialic_acid.csv=0.6513213
phospholipid_human.csv=0.6511704
heparin.csv=0.65116614
heparan_sulfate.csv=0.65096885
protein_folding.csv=0.65091646
glycine.csv=0.6508721
Click to expand...
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 :

complement_system.csv=1.0956763
c1q.csv=1.0956678
mannose.csv=1.0956457
lectin.csv=1.0954727
opsonins.csv=1.0929536
phagocytosis.csv=1.0900666
igm.csv=1.0802875
immune_response.csv=1.0779979
iga.csv=1.0777266
igg.csv=1.0756702
cd14.csv=1.0716493
glycans.csv=1.0657637
tlr.csv=1.0656389
albumin.csv=1.065573
ischemia_reperfusion.csv=1.0651758
human_proteinuria.csv=1.0650758
collagen.csv=1.064805
primary_immunodeficiency.csv=1.0630374
glycosylation.csv=1.0630168
glycoproteins.csv=1.0627177
n_acetylglucosamine.csv=1.0621817
inflammatory_response.csv=1.0612639
macrophage.csv=1.0609236
dendritic_cells.csv=1.0594876
lipopolysaccharide.csv=1.0582732
sialic_acid.csv=1.0554981
hla.csv=1.0483851
thrombospondin.csv=1.0482012
denaturation.csv=1.0451741
il_6.csv=1.0449578
inflammatory_cytokines.csv=1.0404971
amyloid.csv=1.034866
tnf_alpha.csv=1.0335709
neutropenia.csv=1.0333977
interferon_gamma.csv=1.0254595
nlinkedglycosylation.csv=1.0239666
biotin.csv=1.0235858
il_10.csv=1.0218573
liver_disease.csv=1.0209241
sepsis.csv=1.0179111
cardiolipin.csv=1.0150965
histolytica.csv=1.0149822
microglia.csv=1.0145035
hypogammaglobulynemia.csv=1.0136683
Click to expand...


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)
 
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