Human Leukocyte Antigen alleles associated with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

Lande, Asgeir; Fluge, Øystein; Strand, Elin Bolle; Flåm, Siri Tennebø; Sosa, Daisy D.; Mella, Olav; Egeland, Torstein; Saugstad, Ola Didrik; Lie, Benedicte A.; Viken, Marte K.

doi:10.1038/s41598-020-62157-x

Cited by 23 publications

(33 citation statements)

References 51 publications

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“…The carrier frequency of any of these HLA risk alleles was 30% among ME/CFS patients in this trial, which is higher than the 19.1% reported in the recent study of 426 Norwegian ME/CFS patients (30). Western Norway is well represented in this large cohort, and the frequency of DQB1 * 03:03 and C * 07:04 from Western Norway sources did not differ from the national frequency (data not shown).…”

Section: Discussioncontrasting

confidence: 65%

“…The immunologically important Human Leukocyte Antigen (HLA) genes were previously investigated in small ME/CFS cohorts, and certain class II alleles have been found more prevalent among patients (27)(28)(29). A recent study of a larger Norwegian cohort of patients and controls, identified two potential HLA risk alleles, namely HLA-C * 07:04 and HLA-DQB1 * 03:03 (30).…”

Section: Myalgicmentioning

confidence: 99%

“…High-resolution HLA genotyping was conducted as part of a larger study (30). In short, HLA-A, -B, -C, -DRB1, -DQB1, -DQA1, and -DPB1 alleles were genotyped using NGSgo kits and NGSengine software from GenDX (Utrecht, the Netherlands), and 2 × 150 bp paired-end sequencing on a Miseq instrument (Illumina, San Diego, USA) at the Norwegian Sequencing Centre, Oslo.…”

Section: Hla Typingmentioning

confidence: 99%

“…The association analysis between HLA risk alleles and clinical response was not specified in the protocol, and was performed retrospectively in the data analysis phase. Only the potential HLA risk alleles identified by Lande et al (30), i.e., HLA-C * 07:04 and HLA-DQB1 * 03:03, were investigated.…”

Section: Hla Typingmentioning

confidence: 99%

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Intravenous Cyclophosphamide in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. An Open-Label Phase II Study

et al. 2020

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Introduction: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a disease with high symptom burden, of unknown etiology, with no established treatment. We observed patients with long-standing ME/CFS who got cancer, and who reported improvement of ME/CFS symptoms after chemotherapy including cyclophosphamide, forming the basis for this prospective trial. Materials and methods: This open-label phase II trial included 40 patients with ME/CFS diagnosed by Canadian criteria. Treatment consisted of six intravenous infusions of cyclophosphamide, 600-700 mg/m 2 , given at four-week intervals with follow-up for 18 months, extended to 4 years. Response was defined by self-reported improvements in symptoms by Fatigue score, supported by Short Form 36 (SF-36) scores, physical activity measures and other instruments. Repeated measures of outcome variables were assessed by General linear models. Responses were correlated with specific Human Leukocyte Antigen (HLA) alleles. Results: The overall response rate by Fatigue score was 55.0% (22 of 40 patients). Fatigue score and other outcome variables showed significant improvements compared to baseline. The SF-36 Physical Function score increased from mean 33.0 at baseline to 51.5 at 18 months (all patients), and from mean 35.0 to 69.5 among responders. Mean steps per 24 h increased from mean 3,199 at baseline to 4,347 at 18 months (all patients), and from 3,622 to 5,589 among responders. At extended follow-up to 4 years 68% (15 of 22 responders) were still in remission. Patients positive for HLA-DQB1 * 03:03 and/or HLA-C * 07:04 (n = 12) had significantly higher response rate compared to patients negative for these alleles (n = 28), 83 vs. 43%, respectively. Nausea and constipation were common grade 1-2 adverse events. There were one suspected unexpected serious adverse reaction (aggravated POTS) and 11 serious adverse events in eight patients. Conclusion: Intravenous cyclophosphamide treatment was feasible for ME/CFS patients and associated with an acceptable toxicity profile. More than half of the patients Rekeland et al. Intravenous Cyclophosphamide in ME/CFS responded and with prolonged follow-up, a considerable proportion of patients reported ongoing remission. Without a placebo group, clinical response data must be interpreted with caution. We nevertheless believe a future randomized trial is warranted.

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Section: Discussioncontrasting

confidence: 65%

Section: Myalgicmentioning

confidence: 99%

Section: Hla Typingmentioning

confidence: 99%

Section: Hla Typingmentioning

confidence: 99%

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Intravenous Cyclophosphamide in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. An Open-Label Phase II Study

et al. 2020

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“…Their genes exhibit extreme population polymorphism and certain HLA types are genetically predisposed to particular autoimmune diseases ( 29 ). Two independent HLA types tagged by HLA-C*07:04 or HLA-DQB1*03:03 were recently shown to be significantly associated with ME/CFS status (Canadian consensus criteria) ( 30 ). These alleles are each carried by ~ 10% of ME/CFS individuals and alter risk by ∼1.5–2.0-fold.…”

Section: Mitochondrial and Human Leukocyte Antigen Geneticsmentioning

confidence: 99%

Genetic risk factors of ME/CFS: a critical review

Dibble

McGrath²,

Ponting

2020

Human Molecular Genetics

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Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex multisystem illness that lacks effective therapy and a biomedical understanding of its causes. Despite a prevalence of approximately 0.2–0.4% and its high public health burden, and evidence that it has a heritable component, ME/CFS has not yet benefited from the advances in technology and analytical tools that have improved our understanding of many other complex diseases. Here we critically review existing evidence that genetic factors alter ME/CFS risk before concluding that most ME/CFS candidate gene associations are not replicated by the larger CFS cohort within UK Biobank. Multiple genome-wide association studies of this cohort also have not yielded consistently significant associations. Ahead of upcoming larger genome-wide association studies we discuss how these could generate new lines of enquiry into the DNA variants, genes and cell-types that are causally involved in ME/CFS disease.

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Genetics of COVID‐19 and myalgic encephalomyelitis/chronic fatigue syndrome: a systematic review

Tziastoudi

Cholevas

Stefanidis

et al. 2022

Ann Clin Transl Neurol

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COVID‐19 and ME/CFS present with some similar symptoms, especially physical and mental fatigue. In order to understand the basis of these similarities and the possibility of underlying common genetic components, we performed a systematic review of all published genetic association and cohort studies regarding COVID‐19 and ME/CFS and extracted the genes along with the genetic variants investigated. We then performed gene ontology and pathway analysis of those genes that gave significant results in the individual studies to yield functional annotations of the studied genes using protein analysis through evolutionary relationships (PANTHER) VERSION 17.0 software. Finally, we identified the common genetic components of these two conditions. Seventy‐one studies for COVID‐19 and 26 studies for ME/CFS were included in the systematic review in which the expression of 97 genes for COVID‐19 and 429 genes for ME/CFS were significantly affected. We found that ACE, HLA‐A, HLA‐C, HLA‐DQA1, HLA‐DRB1, and TYK2 are the common genes that gave significant results. The findings of the pathway analysis highlight the contribution of inflammation mediated by chemokine and cytokine signaling pathways, and the T cell activation and Toll receptor signaling pathways. Protein class analysis revealed the contribution of defense/immunity proteins, as well as protein‐modifying enzymes. Our results suggest that the pathogenesis of both syndromes could involve some immune dysfunction.

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Human Leukocyte Antigen alleles associated with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

Cited by 23 publications

References 51 publications

Intravenous Cyclophosphamide in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. An Open-Label Phase II Study

Intravenous Cyclophosphamide in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. An Open-Label Phase II Study

Genetic risk factors of ME/CFS: a critical review

Genetics of COVID‐19 and myalgic encephalomyelitis/chronic fatigue syndrome: a systematic review

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