April 2025
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18 Reads
European Journal of Pediatrics
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April 2025
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18 Reads
European Journal of Pediatrics
December 2024
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100 Reads
Background: Epstein-Barr virus (EBV) infection is a known trigger and risk factor for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and post-COVID syndrome (PCS). In previous studies, we found enhanced IgG reactivity to EBV EBNA4 and EBNA6 arginine-rich sequences in postinfectious ME/CFS (piME/CFS). Objective: This study aims to investigate IgG responses to arginine-rich (poly-R) EBNA4 and EBNA6 sequences and homologous human sequences in PCS and ME/CFS. Methods: The IgG responses against poly-R EBNA4 and EBNA6 and corresponding homologous human 15-mer peptides and respective full-length proteins were analyzed using a cytometric bead array (CBA) and a multiplex dot-blot assay. Sera of 45 PCS patients diagnosed according to WHO criteria, with 26 patients fulfilling the Canadian Consensus criteria for ME/CFS (pcME/CFS), 36 patients with non-COVID post-infectious ME/CFS (piME/CFS), and 34 healthy controls (HC) were investigated. Results: Autoantibodies to poly-R peptide sequences of the neuronal antigen SRRM3, the ion channel SLC24A3, TGF-β signaling regulator TSPLY2, angiogenic regulator TSPYL5, as well as to full-length α-adrenergic receptor (ADRA) proteins were more frequent in patients. Several autoantibodies were positively associated with key symptoms of autonomic dysfunction, fatigue, cognition, and pain. Conclusion: Collectively, we identified autoantibodies with new antigen specificities with a potential role in PCS and ME/CFS. Clinical Implication: These finding should prompt further studies on the function of these autoantibodies, their exploitation for diagnostic use, and of drugs targeting autoantibodies.
November 2024
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48 Reads
JMIR Research Protocols
Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) presents significant challenges for affected children and adolescents, their social environment, and treating physicians, due to its profound impact on quality of life and the lack of causal therapeutic approaches. One crucial aspect of care that has been missing for these patients is comprehensive education for both them and their social circles.
October 2024
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68 Reads
October 2024
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18 Reads
September 2024
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30 Reads
September 2024
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420 Reads
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7 Citations
Infection
Background A considerable number of patients who contracted SARS-CoV-2 are affected by persistent multi-systemic symptoms, referred to as Post-COVID Condition (PCC). Post-exertional malaise (PEM) has been recognized as one of the most frequent manifestations of PCC and is a diagnostic criterion of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Yet, its underlying pathomechanisms remain poorly elucidated. Purpose and methods In this review, we describe current evidence indicating that key pathophysiological features of PCC and ME/CFS are involved in physical activity-induced PEM. Results Upon physical activity, affected patients exhibit a reduced systemic oxygen extraction and oxidative phosphorylation capacity. Accumulating evidence suggests that these are mediated by dysfunctions in mitochondrial capacities and microcirculation that are maintained by latent immune activation, conjointly impairing peripheral bioenergetics. Aggravating deficits in tissue perfusion and oxygen utilization during activities cause exertional intolerance that are frequently accompanied by tachycardia, dyspnea, early cessation of activity and elicit downstream metabolic effects. The accumulation of molecules such as lactate, reactive oxygen species or prostaglandins might trigger local and systemic immune activation. Subsequent intensification of bioenergetic inflexibilities, muscular ionic disturbances and modulation of central nervous system functions can lead to an exacerbation of existing pathologies and symptoms.
June 2024
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453 Reads
June 2024
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47 Reads
Virology Journal
Background Infection with the Epstein-Barr virus (EBV) elicits a complex T-cell response against a broad range of viral proteins. Hence, identifying potential differences in the cellular immune response of patients with different EBV-associated diseases or different courses of the same disorder requires interrogation of a maximum number of EBV antigens. Here, we tested three novel EBV-derived antigen formulations for their ability to reactivate virus-specific T cells ex vivo in patients with EBV-associated infectious mononucleosis (IM). Methods We comparatively analyzed EBV-specific CD4+ and CD8+ T-cell responses to three EBV-derived antigen formulations in 20 pediatric patients during the early phase of IM: T-activated EBV proteins (BZLF1, EBNA3A) and EBV-like particles (EB-VLP), both able to induce CD4+ and CD8+ T-cell responses ex vivo, as well as an EBV-derived peptide pool (PP) covering 94 well-characterized CD8+ T-cell epitopes. We assessed the specificity, magnitude, kinetics, and functional characteristics of EBV-specific immune responses at two sequential time points (v1 and v2) within the first six weeks after IM symptom onset (Tonset). Results All three tested EBV-derived antigen formulations enabled the detection of EBV-reactive T cells during the early phase of IM without prior T-cell expansion in vitro. EBV-reactive CD4+ and CD8+ T cells were mainly mono-functional (CD4+: mean 64.92%, range 56.15-71.71%; CD8+: mean 58.55%, range 11.79-85.22%) within the first two weeks after symptom onset (v1) with IFN-γ and TNF-secreting cells representing the majority of mono-functional EBV-reactive T cells. By contrast, PP-reactive CD8+ T cells were primarily bi-functional (>60% at v1 and v2), produced IFN-γ and TNF and had more tri-functional than mono-functional components. We observed a moderate correlation between viral load and EBNA3A, EB-VLP, and PP-reactive CD8+ T cells (rs = 0.345, 0.418, and 0.356, respectively) within the first two weeks after Tonset, but no correlation with the number of detectable EBV-reactive CD4+ T cells. Conclusions All three EBV-derived antigen formulations represent innovative and generic recall antigens suitable for monitoring EBV-specific T-cell responses ex vivo. Their combined use facilitates a thorough analysis of EBV-specific T-cell immunity and allows the identification of functional T-cell signatures linked to disease development and severity.
May 2024
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178 Reads
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1 Citation
Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating multisystemic disease characterized by a complex, incompletely understood etiology. Methods: To facilitate future clinical and translational research, a multicenter German ME/CFS registry (MECFS-R) was established to collect comprehensive, longitudinal, clinical, epidemiological, and laboratory data from adults, adolescents, and children in a web-based multilayer-secured database. Results: Here, we present the research protocol and first results of a pilot cohort of 174 ME/CFS patients diagnosed at two specialized tertiary fatigue centers, including 130 (74.7%) adults (mean age 38.4; SD 12.6) and 43 (25.3%) pediatric patients (mean age 15.5; SD 4.2). A viral trigger was identified in 160/174 (92.0%) cases, with SARS-CoV-2 in almost half of them. Patients exhibited severe functional and social impairment, as reflected by a median Bell Score of 30.0 (IQR 30.0 to 40.0) and a poor health-related quality of life assessed with the Short Form-36 health survey, resulting in a mean score of 40.4 (SD 20.6) for physical function and 59.1 (SD 18.8) for mental health. Conclusions: The MECFS-R provides important clinical information on ME/CFS to research and healthcare institutions. Paired with a multicenter biobank, it facilitates research on pathogenesis, diagnostic markers, and treatment options. Trial registration: ClinicalTrials.gov NCT05778006.
... Although the exact pathophysiology underlying PCS is still unknown, discussed pathways include microvascular alterations and immunometabolic interactions [10] autoimmunology, chronic inflammation, viral persistence, direct organ damage, endothelial dysfunction, or metabolic changes [11]. Female sex, older age, and higher BMI were associated with an increased risk of developing PCS in a recent meta-analysis [12]. ...
September 2024
Infection
... However, only 15 out of 204 countries attained a 20% reduction in the incidence of TB, and only 17 countries achieved a 35% reduction in TB mortality from 2015 to 2020. It is time for countries to revisit their End TB targets to achieve TB control by 2035 [4]. ...
Reference:
Clinical Aspects of Infectious Diseases
May 2024
... Neben den akuten Symptomen weisen immer mehr wissenschaftliche Arbeiten darauf hin, dass SARS-CoV-2-Infektionen und COVID bleibende Gesundheitsprobleme verursachen [5,9]. Für die Betroffenen besonders einschneidend sind dabei Long-COVID [6] und ME/CFS [7]. Long-COVID wird bei ca. ...
May 2024
Wiener klinische Wochenschrift
... There is uncertainty about recommendations for exercise and activity in LC and ME/CFS. Study results show heterogeneous results with a not very robust study situation [36,37]. On the one hand, study results suggest improvement with rehabilitation, but on the other hand, there is also evidence of worsening of symptoms in terms of postexertional malaise in subgroups with overexertion. ...
April 2024
Sports Medicine - Open
... Hematopoietic cell transplantation (HCT) offers curative potential for conditions such as refractory leukemia [1,2], bone marrow failure syndromes [3], immune deficiencies [4,5], and inborn errors of metabolism [6]. However, intensive conditioning regimens and post-transplant immune responses often result in severe, sometimes life-threatening complications, necessitating effective management strategies to improve post-transplant survival. ...
April 2024
Blood
... An overview of the items is provided in the supplement (Table S1). The questionnaire has been used in previous studies [7,17,45], where weak to moderate significant correlations between the perceived overall pandemic burden and the specific pandemic-related constraints as well as between the pandemic-related items with parenting stress, child and parental psychopathology were identified [7]. For this study, correlations between the pandemic-related items, separated by group, can be found in the supplement (Table S2). ...
March 2024
... These symptoms persist for at least two months without any other explanation. They may be the same as in the acute phase of the disease or completely different [11]. [3]. ...
January 2024
European Journal of Pediatrics
... However, studies have shown that the prevalence of MS in patients with IM is three times higher than in the general population, with strong associations in long intervals of more than 5 years [32]. Myalgic encephalomyelitis/ chronic fatigue syndrome (ME/CFS) after EBV-IM is a severely debilitating disease with a delayed clinical diagnosis that has a more significant impact on physical functioning and health-related quality of life in adolescent patients [43]. Eighty per cent of patients with splenic rupture or infarction present with symptoms of IM before 3 weeks of onset [44]. ...
January 2024
... Additionally, there are a number of criteria catalogs for diagnosing ME/CFS based on the symptoms present; the rather unspecific 1994 Centers for Disease Control and Prevention (CDC) Fukuda criteria (known as CDC or Fukuda criteria) [18] have been replaced by the Canadian Consensus Criteria (CCC), Criteria of the Institute of Medicine (IOM), or the International Consensus Criteria (ICC) [19][20][21][22]. Additionally, a variety of questionnaire tools (e.g., Munich Berlin Symptom Questionnaire (MBSQ) [23], DePaul Symptom Questionnaire (PSQ) [24]) are available for clinical practice. ...
December 2023
European Journal of Pediatrics
... In contrast, the prolonged disruption of normal sleep can contribute to neuroinflammation [168], norepinephrine-stimulated degeneration of the locus coeruleus, and hippocampal amyloid-β 42 accumulation, with the potential to cause memory dysfunction and CD [169]. Unfortunately, the use of benzodiazepines, while sometimes reducing the time to fall asleep and helpful initially [170], frequently causes daytime drowsiness and can exacerbate CD in ME/CFS. Melatonin, however, is more suitable, can encourage the normalisation of sleep chronobiology, and has the ability to scavenge reactive oxygen species that are central to neuroinflammation [171]. ...
September 2023
Autoimmunity Reviews