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

Steiner, Sophie; Becker, S; Hartwig, Jelka; Sotzny, Franziska; Lorenz, Siegfried; Bauer, Sandra; Löbel, Madlen; Stittrich, Anna Barbara; Grabowski, Patricia; Scheibenbogen, Carmen

doi:10.3389/fimmu.2020.00578

Cited by 33 publications

(39 citation statements)

References 48 publications

(68 reference statements)

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“…17 Depression and sleepiness were assessed by Patient Health Questionnaire 9 (PHQ9) and Epworth Sleepiness Scale (ESS). According to PHQ9 patients were classified as minimal depressive symptoms (1-4), mild depressive symptoms (5-9), moderate depressive symptoms (10)(11)(12)(13)(14), moderately severe depressive symptoms (15)(16)(17)(18)(19), or severe depressive symptoms (20)(21)(22)(23)(24)(25)(26)(27). According to ESS patients were classified as no evidence of sleep apnea 0-9, possible mild to moderate sleep apnea 11-15, >16 possible severe sleep apnea.…”

Section: Disability and Daily Physical Function Was Assessed By Bellmentioning

confidence: 99%

“…13 There is emerging evidence that post-infectious ME/CFS has an autoimmune mechanism and dysfunctional autoantibodies to natural regulatory antibodies against adrenergic receptors were described. [13][14][15] We report here on the first results of our ongoing study initiated at Charité in July 2020 to characterize patients with persistent fatigue and other symptoms following mild to moderate COVID-19 and to assess if they meet diagnostic criteria for ME/CFS. Due to the complexity of symptoms patients were comprehensively evaluated by a team from various disciplines including clinical immunology, rheumatology, neurology, cardiology, and pneumology with long experience in diagnosing ME/CFS (https://cfc.charite.de).…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Chronic COVID-19 Syndrome and Chronic Fatigue Syndrome (ME/CFS) following the first pandemic wave in Germany – a first analysis of a prospective observational study

Kedor

Freitag

Meyer-Arndt

et al. 2021

Preprint

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Objective: Characterization of the clinical features of patients with persistent symptoms after mild to moderate COVID-19 infection and exploration of factors associated with the development of Chronic COVID-19 Syndrome (CCS). Methods: Setting: Charite Fatigue Center with clinical immunologists and rheumatologist, neurologists and cardiologists at Charite University hospital. Participants: 42 patients who presented with persistent moderate to severe fatigue six months following a mostly mild SARS-CoV-2 infection at the Charite Fatigue Center from July to November 2020. Main outcome measures: The primary outcomes were clinical and paraclinical data and meeting diagnostic criteria for Chronic Fatigue Syndrome (ME/CFS). Relevant neurological and cardiopulmonary morbidity was excluded. Results: The median age was 36.5, range 22-62, 29 patients were female and 13 male. At six months post acute COVID-19 all patients had fatigue (Chalder Fatigue Score median 25 of 33, range 14-32), the most frequent other symptoms were post exertional malaise (n=41), cognitive symptoms (n=40), headache (n=38), and muscle pain (n=35). Most patients were moderately to severely impaired in daily live with a median Bell disability score of 50 (range 15-90) of 100 (healthy) and Short Form 36 (SF36) physical function score of 63 (range 15-80) of 100. 19 of 42 patients fulfilled the 2003 Canadian Consensus Criteria for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). These patients reported more fatigue in the Chalder Fatigue Score (p=0.006), more stress intolerance (p=0.042) and more frequent and longer post exertional malaise (PEM) (p= 0.003), and hypersensitivity to noise (p=0.029), light (p=0.0143) and temperature (0.024) compared to patients not meeting ME/CFS criteria. Handgrip force was diminished in most patients compared to healthy control values, and lower in CCS/CFS compared to non-CFS CCS (Fmax1 p=0.085, Fmax2, p=0.050, Fmean1 p=0.043, Fmean2 p=0.034, mean of 10 repeat handgrips, 29 female patients). Mannose-binding lectin (MBL) deficiency was observed frequently (22% of all patients) and elevated IL-8 levels were found in 43% of patients. Conclusions: Chronic COVID-19 Syndrome at months 6 is a multisymptomatic frequently debilitating disease fulfilling diagnostic criteria of ME/CFS in about half of the patients in our study. Research in mechanisms and clinical trials are urgently needed.

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Section: Disability and Daily Physical Function Was Assessed By Bellmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Chronic COVID-19 Syndrome and Chronic Fatigue Syndrome (ME/CFS) following the first pandemic wave in Germany – a first analysis of a prospective observational study

Kedor

Freitag

Meyer-Arndt

et al. 2021

Preprint

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“…Certainly, these disorders have been described after an adjuvant stimulus (vaccine compounds, silicone implantation, drugs, infections, metals, etc.) among genetically predisposed individuals (mainly the HLA-DRB1 and PTPN22 gene) [ 13 , 14 ], leading to an hyperstimulation of the immune system. As a result, the production of autoantibodies may occur, eventually driving the development of AID [ 15 , 16 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

Classical Examples of the Concept of the ASIA Syndrome

et al. 2020

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Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) was first introduced in 2011 by Shoenfeld et al. and encompasses a cluster of related immune mediated diseases, which develop among genetically prone individuals as a result of adjuvant agent exposure. Since the recognition of ASIA syndrome, more than 4400 documented cases have been reported so far, illustrated by heterogeneous clinical manifestations and severity. In this review, five enigmatic conditions, including sarcoidosis, Sjögren’s syndrome, undifferentiated connective tissue disease, silicone implant incompatibility syndrome (SIIS), and immune-related adverse events (irAEs), are defined as classical examples of ASIA. Certainly, these disorders have been described after an adjuvant stimulus (silicone implantation, drugs, infections, metals, vaccines, etc.) among genetically predisposed individuals (mainly the HLA-DRB1 and PTPN22 gene), which induce an hyperstimulation of the immune system resulting in the production of autoantibodies, eventually leading to the development of autoimmune diseases. Circulating autonomic autoantibodies in the sera of patients with silicone breast implants, as well as anatomopathological aspects of small fiber neuropathy in their skin biopsies have been recently described. To our knowledge, these novel insights serve as a common explanation to the non-specific clinical manifestations reported in patients with ASIA, leading to the redefinition of the ASIA syndrome diagnostic criteria.

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“…There is increasing evidence for an autoimmune pathomechanism in ME/CFS [ 6 ]. Autoimmunity-related risk variants in PTPN22 and CTLA4 were found to be associated with ME/CFS with infectious onset in a recent study [ 7 ]. Several studies described autoantibodies in ME/CFS, including antibodies against nuclear and membrane structures, cardiolipin, neurotransmitter receptors, and against autoantigens formed by oxidative or nitrosative damage [ 6 , 8 , 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Efficacy of Repeat Immunoadsorption

Tölle

Freitag

Antelmann

et al. 2020

JCM

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(1) Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex neuroimmunological disease. There is evidence for an autoimmune mechanism for ME/CFS with an infection-triggered onset and dysfunction of ß2-adrenoreceptor antibodies (ß2AR-AB). In a first proof-of-concept study, we could show that IA was effective to reduce ß2AR-AB and led to improvement of various symptoms. (2) Five of the ME/CFS patients who had clinical improvement following treatment with a five-day IA were retreated in the current study about two years later with a modified IA protocol. The severity of symptoms was assessed by disease specific scores during a follow-up period of 12 months. The antibodies were determined by ELISA. (3) The modified IA treatment protocol resulted in a remarkable similar clinical response. The treatment was well tolerated and 80–90% decline of total IgG and ß2AR-AB was achieved. Four patients showed a rapid improvement in several clinical symptoms during IA therapy, lasting for six to 12 months. One patient had no improvement. (4) We could provide further evidence that IA has clinical efficacy in patients with ME/CFS. Data from our pilot trial warrant further controlled studies in ME/CFS.

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

Cited by 33 publications

References 48 publications

Chronic COVID-19 Syndrome and Chronic Fatigue Syndrome (ME/CFS) following the first pandemic wave in Germany – a first analysis of a prospective observational study

Chronic COVID-19 Syndrome and Chronic Fatigue Syndrome (ME/CFS) following the first pandemic wave in Germany – a first analysis of a prospective observational study

Classical Examples of the Concept of the ASIA Syndrome

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Efficacy of Repeat Immunoadsorption

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