Autoimmunity-Related Risk Variants in PTPN22 and CTLA4 Are Associated With ME/CFS With Infectious Onset

[gbells]

I found some information on genetic mutations that trigger ME when people are exposed to chronic viruses. Previously I shared an article about MTHFR mutations that also do this by impairing folate availability to provide ubiquinol. In this case the proteins made trigger hyper-responsiveness in the immune response and predispose to autoimmune disease (lupus, etc).

Single nucleotide polymorphisms (SNP) in various genes have been described to be associated with susceptibility to autoimmune disease. In this study, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) patients and controls were genotyped for five immune gene SNPs in tyrosine phosphatase non-receptor type 22 (PTPN22, rs2476601), cytotoxic T-lymphocyte-associated protein 4 (CTLA4, rs3087243), tumor necrosis factor (TNF, rs1800629 and rs1799724), and interferon regulatory factor 5 (IRF5, rs3807306), which are among the most important risk variants for autoimmune diseases. Analysis of 305 ME/CFS patients and 201 healthy controls showed significant associations of the PTPN22 rs2476601 and CTLA4 rs3087243 autoimmunity-risk alleles with ME/CFS. The associations were only found in ME/CFS patients, who reported an acute onset of disease with an infection (PTPN22 rs2476601: OR 1.63, CI 1.04-2.55, p = 0.016; CTLA4 rs3087243: OR 1.53, CI 1.17-2.03, p = 0.001), but not in ME/CFS patients without infection-triggered onset (PTPN22 rs2476601: OR 1.09, CI 0.56-2.14, p = 0.398; CTLA4 rs3087243: OR 0.89, CI 0.61-1.30, p = 0.268). This finding provides evidence that autoimmunity might play a role in ME/CFS with an infection-triggered onset. Both genes play a key role in regulating B and T cell activation.

-Steiner S, Becker SC, Hartwig J, Sotzny F, Lorenz S, Bauer S, Löbel M, Stittrich AB, Grabowski P, Scheibenbogen C. Autoimmunity-Related Risk Variants in PTPN22 and CTLA4 Are Associated With ME/CFS With Infectious Onset. Front Immunol. 2020 Apr 9;11:578. doi: 10.3389/fimmu.2020.00578. PMID: 32328064; PMCID: PMC7161310.

PTPN22 mutation gives, "increased risk of Type 1 Diabetes, rheumatoid arthritis, lupus, Vitiligo and Graves' disease, but a decreased risk of Crohn's disease."

https://www.wikiwand.com/en/PTPN22

 

[Springbok1988]

Thank you for sharing this! I just pulled up my genetic data and found I am homozygous for the PTPN2 rs2476601 mutation and heterozygous for the CTLA4 rs3087243 mutation. My ME journey began with a coxsackie B infection so this makes a lot of sense.

 

[Boba]

Hey. What does homo and heterozygous mean? And which implies that you habe mutations? Thanks!!

 

[Springbok1988]

You have two copies of each gene. You get one copy from your mother and the other from your father. If both copies are the same (ie they both don’t have a mutation or both do have a mutation), it is called homozygous. If the copy from one parent is different from the copy from the other (one has a mutation and the other doesn’t), then it is called heterozygous.
That’s a bit of an over simplification but I think it should help clarify what it means.

 

[Boba]

Ok thanks. I just checked mine an they are GG for PTP and AG for CTL. Is this the same for you? I attached a slide from a presentation from Scheibenbogen one of the authors. She showed that AG for PTP and AG for CTL are the autoimmune ones.

 

[Springbok1988]

Oops! I just read the abstract and thought they meant homozygous individuals were at higher risk. But yes, you and I have the same result. So it looks like this doesn’t help explain my situation, after all.

The paper shows:
PTPN22 rs2476601 AG increased risk
CTLA4 rs3087243 GG increased risk

 

[gbells]

You have two copies of each gene. You get one copy from your mother and the other from your father. If both copies are the same (ie they both don’t have a mutation or both do have a mutation), it is called homozygous. If the copy from one parent is different from the copy from the other (one has a mutation and the other doesn’t), then it is called heterozygous.
That’s a bit of an over simplification but I think it should help clarify what it means.

With folic acid related genes as long as you are heterozygous you should be ok UNLESS you get infected with chronic viruses which can impair it. Those patients benefit from methyl folate. Unfortunately medicine doesn't recommend checking folic acid metabolism genes and doesn't recommend this for ME patients.

 

[Boba]

Thanks for your input! Which genes would this be? A chronic virus is sth like HSV 1 or HPV?

 

[cfs since 1998]

I don't understand genetics too well, so rs2476601 "GG" is normal?