Multi-ancestry GWAS of [LC] identifies immune-related loci and etiological links to [CFS], fibromyalgia and depression, 2024, Chaudhary et al

[forestglip]

• Molecular study of receptor for [AGE] gene promoter and identification of specific HLA haplotypes possibly involved in [CFS], 2009, Carlo-Stella et al

The haplotypes RAGE-374T, DRB1*04; RAGE-374T, DRB1*09; RAGE-374T, DRB1*11; RAGE-374A, DRB1*13; RAGE-429T, DRB1*04 and RAGE-429C, DRB1*11 were significantly more frequent in CFS patients, whereas RAGE-429C, DRB1*07 would seem protective. A significantly lower frequency of DRB1*1104 (5.4% vs 12.9% p=0.04, OR=0.39) and a significantly higher frequency of HLA-DRB1*1301 (13.0% vs 5.1% p=0.006, OR= 2.79) were found in CFS patients. A synergic effect was observed with RAGE polymorphism. The OR values strengthened in the following cis combinations: RAGE-374A, HLA-DRB1*1104 (OR=0.27) and RAGE-374A, HLADRB1*1301 (OR=6.23).

patients were recruited through the two referral centers in Italy for CFS [...] All of these centers use the Fukuda criteria for the diagnosis of CFS.

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• Autoantibodies, Polymorphisms in the Serotonin Pathway, and Human Leukocyte Antigen Class II Alleles in [CFS], 2009, Ortega-Hernandez et al

An age at CFS onset (ACFSO) during the third decade of life was associated with the serotonin receptor AA genotype and the HLA-DRB1*03 allele. An ACFSO during the fourth decade of life was associated with the HLA-DRB1*07 allele

Italian patients diagnosed by means of Fukuda criteria affering to “CFS Biological Bank” of Immunogenetics Laboratory and Department of Genetic and Micribiology, University of Pavia were enrolled.

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• Human Leukocyte Antigen alleles associated with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Fluge, Mella et al 2020

We performed high resolution HLA -A, -B, -C, -DRB1, -DQB1 and -DPB1 genotyping by next generation sequencing in 426 adult, Norwegian ME/CFS patients, diagnosed according to the Canadian Consensus Criteria. HLA associations were assessed by comparing to 4511 healthy and ethnically matched controls. [...] We discovered two independent HLA associations, tagged by the alleles HLA-C*07:04 (OR 2.1 [95% CI 1.4–3.1]) and HLA-DQB1*03:03 (OR 1.5 [95% CI 1.1–2.0]).

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Thanks to this Phoenix Rising post for listing previous HLA findings.

 

[Vlad83]

I am puzzled by how common these variants are in the general population. Per the paper, the effect alleles for the HLA variant is 74% and for BPTF it's 77%.. This would make most people susceptible, or am I reading this wrong?

 

[SNT Gatchaman]

In May 2023, in thread Ron Davis’s big immune study is looking at HLA genes [...]

From https://reporter.nih.gov/project-details/9577948

Project Start Date 15-June-2018
Project End Date 31-May-2023
Budget Start Date 15-June-2018
Budget End Date 31-May-2019

So the projected end of the project was the end of this month, so yes, if that schedule is being kept to, then we might be able to expect the results some time after the end of this month. How long after will depend on how long it takes to write it all up, how long it takes to get a journal to accept it, get it peer reviewed, and then finally publish it.

It would be great to see the results soon.

 

[SNT Gatchaman]

See also Immune exhaustion in ME/CFS and long COVID (2024, JCI Insight)

HLA-DQA1, HLA-DQB1, and IGHG1 were found to be pivotal in the top biological pathways and diseases in long COVID, which overlapped with ME/CFS with the addition of IGHG3, CCL2, CEACAM3, and IFNA6.