Article
Multidisciplinary Sciences
Bindu D. Paul, Marian D. Lemle, Anthony L. Komaroff, Solomon H. Snyder
Summary: The review summarizes evidence of biological abnormalities in patients with acute COVID-19 and ME/CFS, including redox imbalance, systemic inflammation, neuroinflammation, impaired ATP generation, and general hypometabolism. Although these phenomena have not been extensively studied in individuals with long COVID-19, understanding these abnormalities may lead to the development of novel therapeutics.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Medicine, General & Internal
Rebekah Maksoud, Chandi Magawa, Natalie Eaton-Fitch, Kiran Thapaliya, Sonya Marshall-Gradisnik
Summary: This systematic review aimed to evaluate potential biomarkers that could effectively differentiate ME/CFS patients from healthy controls. A total of 101 studies were included, and potential biomarkers ranged from genetic/epigenetic, immunological, metabolomics/mitochondrial/microbiome, endovascular/circulatory, neurological, ion channel, to physical dysfunction biomarkers. The findings indicated evidence of immune dysfunction in ME/CFS and the use of lymphocytes as a model to investigate the pathomechanism of the illness.
Article
Biochemistry & Molecular Biology
Irene Soffritti, Sabine Gravelsina, Maria D'Accolti, Francesca Bini, Eleonora Mazziga, Anda Vilmane, Santa Rasa-Dzelzkaleja, Zaiga Nora-Krukle, Angelika Krumina, Modra Murovska, Elisabetta Caselli
Summary: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex disease without diagnostic biomarkers, but there is evidence supporting a role of herpesviruses and microRNAs in its development. This study found that six out of eight selected microRNAs were differently expressed in ME/CFS patients compared to healthy controls. The levels of these microRNAs correlated with disease severity but not with pro-inflammatory cytokines or HHV-6A/6B genome levels. These results suggest that microRNAs could serve as potential biomarkers and provide insights into ME/CFS pathogenic mechanisms.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Medicine, Research & Experimental
Rebekah Maksoud, Cassandra Balinas, Sean Holden, Helene Cabanas, Donald Staines, Sonya Marshall-Gradisnik
Summary: There is currently insufficient evidence on the effectiveness of mitochondrial-targeting nutraceuticals in treating ME/CFS patients. Future well-designed studies are needed to clarify the involvement of mitochondria in the pathomechanism of ME/CFS and the impact of mitochondrial-modifying agents on illness severity.
JOURNAL OF TRANSLATIONAL MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Varvara A. A. Ryabkova, Natalia Y. Y. Gavrilova, Alina A. A. Poletaeva, Alexander I. I. Pukhalenko, Irina A. A. Koshkina, Leonid P. P. Churilov, Yehuda Shoenfeld
Summary: Recent studies suggest that antibody-mediated autoimmune mechanisms may play a role in fibromyalgia (FM) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), specifically in relation to G protein-coupled receptors. However, the full extent of the natural antibody network and its implications in these disorders has not been fully explored.
Article
Immunology
Leonard A. Jason, Joseph Cotler, Mohammed F. Islam, Madison Sunnquist, Ben Z. Katz
Summary: This study investigated potential predictors of developing chronic fatigue syndrome (ME/CFS) in university students six months after developing infectious mononucleosis (IM). The research found that ME/CFS patients had more physical symptoms and immune irregularities before onset, but no significant differences in psychological symptoms compared to those who recovered.
CLINICAL INFECTIOUS DISEASES
(2021)
Article
Medicine, Research & Experimental
Ludovic Giloteaux, Jiayin Li, Mady Hornig, W. Ian Lipkin, David Ruppert, Maureen R. R. Hanson
Summary: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex disease characterized by unexplained fatigue and other symptoms. This study found increased levels of extracellular vesicles (EVs) and IL2 cytokine in plasma of ME/CFS patients. The correlations between specific proteins and clinical data suggest immune response and hemostasis dysfunctions in ME/CFS.
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
Article
Virology
Thomas Briese, Rafal Tokarz, Lucinda Bateman, Xiaoyu Che, Cheng Guo, Komal Jain, Vishal Kapoor, Susan Levine, Mady Hornig, Alexandra Oleynik, Phenix-Lan Quan, Wai H. Wong, Brent L. Williams, Suzanne D. Vernon, Nancy G. Klimas, Daniel L. Peterson, Jose G. Montoya, Walter Ian Lipkin
Summary: This multicenter study found no consistent group-specific differences in viral nucleic acid presence in ME/CFS patients compared to healthy controls, except for a lower prevalence of anelloviruses. Future investigations into viral infections in ME/CFS should focus on adaptive immune responses rather than surveillance for viral gene products.
JOURNAL OF MEDICAL VIROLOGY
(2023)
Article
Immunology
Franz Martin, Manuel Blanco-Suarez, Paola Zambrano, Oscar Caceres, Miriam Almirall, Jose Alegre-Martin, Beatriz Lobo, Ana Maria Gonzalez-Castro, Javier Santos, Joan Carles Domingo, Joanna Jurek, Jesus Castro-Marrero
Summary: This study found that biomarkers of intestinal barrier function and inflammation are associated with autonomic dysfunction in patients with fibromyalgia and myalgic encephalomyelitis/chronic fatigue syndrome. Anti-beta-lactoglobulin antibodies, zonulin-1, lipopolysaccharides, and soluble CD14 may be potential predictors of intestinal barrier dysfunction in these conditions.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Medicine, Research & Experimental
Inigo Murga, Larraitz Aranburu, Pascual A. Gargiulo, Juan-Carlos Gomez-Esteban, Jose-Vicente Lafuente
Summary: The study reveals that patients with CFS/ME have low maintained attention and significant cognitive fatigue, with deficits in sustained attention and perception of fatigue serving as sensitive and reliable indicators for confirming or ruling out CFS/ME.
JOURNAL OF TRANSLATIONAL MEDICINE
(2021)
Article
Multidisciplinary Sciences
Joao Malato, Franziska Sotzny, Sandra Bauer, Helma Freitag, Andre Fonseca, Anna D. Grabowska, Luis Graca, Clara Cordeiro, Luis Nacul, Eliana M. Lacerda, Jesus Castro-Marrero, Carmen Scheibenbogen, Francisco Westermeier, Nuno Sepulveda
Summary: Patients with ME/CFS show decreased methylation levels in specific CpG probes in the ACE gene locus and the ACE2 gene promoter region, as well as reduced expression of ACE2 compared to healthy controls, indicating a higher risk of COVID-19 infection. This suggests that ME/CFS patients should be prioritized for vaccination. Further research on other human cell entry receptors and cell types targeted by the virus is recommended to support this conclusion.
Review
Immunology
Rahel S. Konig, Werner C. Albrich, Christian R. Kahlert, Lina Samira Bahr, Ulrike Lober, Pietro Vernazza, Carmen Scheibenbogen, Sofia K. Forslund
Summary: Myalgic encephalomyelitis (ME) or Chronic Fatigue Syndrome (CFS) is a neglected, debilitating disease with unclear etiology and pathophysiology. The gut microbiome may play a role in CFS and further research is needed to explore potential diagnostic and therapeutic approaches.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Neurosciences
Irene Tsilioni, Benjamin Natelson, Theoharis C. Theoharides
Summary: This study found that mitochondrial DNA (mtDNA) associated with serum exosomes is increased in ME/CFS patients only after exercise. Moreover, exosomes isolated from ME/CFS patients stimulate significant release of IL-1 beta from cultured human microglia, indicating that activation of microglia by serum-derived exosomes may serve as a potential novel pathogenetic factor and target for treatment of ME/CFS.
EUROPEAN JOURNAL OF NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Lena Lutz, Johanna Rohrhofer, Sonja Zehetmayer, Michael Stingl, Eva Untersmayr
Summary: ME/CFS patients commonly exhibit abnormalities in immune parameters, including deficiencies or reduction as well as immune activation or inflammation. Common abnormalities include antibody deficiencies and low MBL levels.
Review
Pharmacology & Pharmacy
Peter L. Toogood, Daniel J. Clauw, Sameer Phadke, David Hoffman
Summary: ME/CFS is a chronic debilitating disease characterized by severe fatigue, pain, sleep disruption, and cognitive dysfunction. Current treatments focus on symptom management and addressing psychological sequelae, with ongoing efforts towards identifying effective therapies and understanding the mechanistic basis of the disease.
PHARMACOLOGICAL RESEARCH
(2021)
Article
Cell Biology
Amanpreet K. Cheema, Leonor Sarria, Mina Bekheit, Fanny Collado, Eloy Almenar-Perez, Eva Martin-Martinez, Jose Alegre, Jesus Castro-Marrero, Mary A. Fletcher, Nancy G. Klimas, Elisa Oltra, Lubov Nathanson
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
(2020)
Article
Immunology
Elisabet Gomez-Mora, Jorge Carrillo, Victor Urrea, Josepa Rigau, Jose Alegre, Cecilia Cabrera, Elisa Oltra, Jesus Castro-Marrero, Julia Blanco
FRONTIERS IN IMMUNOLOGY
(2020)
Review
Cell & Tissue Engineering
Maria B. Monzon-Nomdedeu, Karl J. Morten, Elisa Oltra
Summary: The study suggests that certain metabolites are commonly altered in the body fluids of patients with FM and ME/CFS. In vitro cell-based assays may serve as screening platforms, providing evidence of factors in patient body fluids capable of altering morphology, differentiation state and/or growth patterns.
WORLD JOURNAL OF STEM CELLS
(2021)
Review
Cell & Tissue Engineering
Victoria Dupuis, Elisa Oltra
Summary: Mesenchymal stem cells (MSCs) have great potential for cell therapy due to their immunomodulatory effects, but their clinical application is restricted by several factors. Induced pluripotent stem cells (iPSCs) offer a new source to generate MSCs, known as iMSCs, which may overcome technical and biological limitations and ethical concerns regarding human embryonic stem cells. Various differentiation methods for iPSCs into MSCs have been developed to meet clinical demands.
WORLD JOURNAL OF STEM CELLS
(2021)
Review
Chemistry, Medicinal
Karen Gimenez-Orenga, Elisa Oltra
Summary: Human endogenous retroviruses (HERVs) are ancient retroviral DNA sequences established in germline, tightly regulated by epigenetic mechanisms, and associated with various diseases including neurological disorders. Promising therapies targeting HERV elements, such as temelimab, offer potential for treating associated diseases.
Article
Medicine, General & Internal
Jesus Castro-Marrero, Mario Zacares, Eloy Almenar-Perez, Jose Alegre-Martin, Elisa Oltra
Summary: This study used unbiased hierarchical cluster analysis of 250 carefully phenotyped female ME/CFS cases to identify three symptom-based clusters with significant differences in five blood parameters. Additionally, high levels of circulating complement factor C1q were found in a subgroup of participants, identifying it as a key molecule for an ME/CFS subtype with more apparent pain symptoms. These results have important implications for ME/CFS etiology research and future diagnosis and treatment methods.
JOURNAL OF CLINICAL MEDICINE
(2021)
Meeting Abstract
Endocrinology & Metabolism
Silvia Alvarez-Cubela, Dagmar Klein, Charles G. Alver, Mirza Muhammad Fahd Qadir, Luciana Mateus Goncalves, Farhan Qureshi, Joana Almaca, Christopher Fraker, Alejandro Caicedo, Alberto Pugliese, Camillo Ricordi, Elisa Oltra, Alberto Pugliese, Ashutosh G. Agarwal, Ricardo Pastori, Juan Dominguez-Bendala
Article
Medicine, General & Internal
Alba Gonzalez-Cebrian, Eloy Almenar-Perez, Jiabao Xu, Tong Yu, Wei E. Huang, Karen Gimenez-Orenga, Sarah Hutchinson, Tiffany Lodge, Lubov Nathanson, Karl J. Morten, Alberto Ferrer, Elisa Oltra
Summary: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is diagnosed clinically and is characterized by persistent fatigue and post-exertional malaise. Differential expression of miRNAs in the blood has been observed in patients, but their diagnostic power is limited. Blood vesicles may carry relevant disease information. Raman micro-spectroscopic analysis identified carotenoid peaks as ME/CFS fingerprints, but their diagnostic capacity is limited. However, Raman data helped refine the number of miRNAs in a previous model, ensuring a perfect classification of subjects.
FRONTIERS IN MEDICINE
(2022)
Article
Immunology
Karen Gimenez-Orenga, Justine Pierquin, Joanna Brunel, Benjamin Charvet, Eva Martin-Martinez, Herve Perron, Elisa Oltra
Summary: Post-COVID-19 condition represents a post-viral syndrome of unprecedented dimensions. The study shows that HERV-W ENV protein can still be actively expressed long after SARS-CoV-2 infection is resolved in post-COVID-19 condition patients. Increased anti-SARS-CoV-2 immunoglobulins, particularly IgE, seems to strongly correlate with deteriorated patient physical function. These findings provide important insights for the characterization and individualized treatment of patients with post-COVID-19 condition.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Derek J. J. Van Booven, Jackson Gamer, Andrew Joseph, Melanie Perez, Oskar Zarnowski, Meha Pandya, Fanny Collado, Nancy Klimas, Elisa Oltra, Lubov Nathanson
Summary: Our study evaluated transcriptomic changes in female ME/CFS patients undergoing an exercise challenge, aiming to precipitate post-exertional malaise (PEM). We found that ME/CFS patients did not show significant gene expression changes under maximal exertion, while healthy controls demonstrated altered gene networks related to immune cell signaling and functions. During the recovery period, female ME/CFS patients showed dysregulated immune signaling pathways and dysfunctional cellular responses to stress. These findings provide a foundation for future research and potential targeted treatments for ME/CFS.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Jackson Gamer, Derek J. Van Booven, Oskar Zarnowski, Sebastian Arango, Mark Elias, Asha Kurian, Andrew Joseph, Melanie Perez, Fanny Collado, Nancy Klimas, Elisa Oltra, Lubov Nathanson
Summary: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex illness characterized by debilitating fatigue and post-exertional malaise. This study found sex differences in gene expression in male and female ME/CFS patients during and after exercise challenge. Male ME/CFS patients showed activation of immune-cell signaling pathways, while female ME/CFS patients had alterations in gene networks related to cell stress and response to herpes viruses.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Meeting Abstract
Hematology
Jurado Tapiador Rebeca, Garcia Calduch Olga, Kaivers Jennifer, Betz Beate, Cid Martinez Paula, Schuler Esther, Orna Montero Elisa, Cabezon Marco Marta, Marce Torra Silvia, De Aguirre Egana Itziar, Jimenez Lorenzo Maria Jose, Ramirez Serrano Jose Luis, Estrada Barreras Natalia, De Jaureguizar Tesas Alejandro, Canelo Vilaseca Marta, Germing Ulrich, Ribera Santasusana Josep Maria, Zamora Plana Lurdes, Xicoy Cirici Blanca
Meeting Abstract
Hematology
De Jaureguizar Tesas Alejandro, Sorigue Tomas Marc, Raya Corbacho Minerva, Vergara Casamar Sara, Granada Font Isabel, Orna Montero Elisa, Mesa Tudel Alba, Grau Cat Javier, Jurado Tapiador Rebeca, Canelo Vilaseca Marta, Huguet Mas Maria, De La Fuente Montes Cristina, Quintela Vilchez David, Jimenez Lorenzo Maria Jose, Ribera Santasusana Josep Maria, Zamora Plana Lourdes, Navarro Ferrando Jose Tomas, Xicoy Cirici Blanca