TY - UNPB
T1 - Increased circulating fibronectin, depletion of natural IgM and heightened EBV, HSV-1 reactivation in ME/CFS and long COVID
AU - Liu, Zheng
AU - Hollmann, Claudia
AU - Kalanidhi, Sharada
AU - Grothey, Arnhild
AU - Keating, Sam
AU - Mena-Palomo, Irene
AU - Lamer, Stephanie
AU - Schlosser, Andreas
AU - Kaiping, Agnes
AU - Scheller, Carsten
AU - Sotzny, Franzeska
AU - Horn, Anna
AU - Nürnberger, Carolin
AU - Cejka, Vladimir
AU - Afshar, Boshra
AU - Bahmer, Thomas
AU - Schreiber, Stefan
AU - Vehreschild, Jörg Janne
AU - Miljukov, Olga
AU - Schäfer, Christian
AU - Kretzler, Luzie
AU - Keil, Thomas
AU - Reese, Jens-Peter
AU - Eichner, Felizitas A
AU - Schmidbauer, Lena
AU - Heuschmann, Peter U
AU - Störk, Stefan
AU - Morbach, Caroline
AU - Riemekasten, Gabriela
AU - Beyersdorf, Niklas
AU - Scheibenbogen, Carmen
AU - Naviaux, Robert K
AU - Williams, Marshall
AU - Ariza, Maria E
AU - Prusty, Bhupesh K
N1 - Paper in collection COVID-19 SARS-CoV-2 preprints from medRxiv and bioRxiv
PY - 2023/6/29
Y1 - 2023/6/29
N2 - Myalgic Encephalomyelitis/ Chronic Fatigue syndrome (ME/CFS) is a complex, debilitating, long-term illness without a diagnostic biomarker. ME/CFS patients share overlapping symptoms with long COVID patients, an observation which has strengthened the infectious origin hypothesis of ME/CFS. However, the exact sequence of events leading to disease development is largely unknown for both clinical conditions. Here we show antibody response to herpesvirus dUTPases, particularly to that of Epstein-Barr virus (EBV) and HSV-1, increased circulating fibronectin (FN1) levels in serum and depletion of natural IgM against fibronectin ((n)IgM-FN1) are common factors for both severe ME/CFS and long COVID. We provide evidence for herpesvirus dUTPases-mediated alterations in host cell cytoskeleton, mitochondrial dysfunction and OXPHOS. Our data show altered active immune complexes, immunoglobulin-mediated mitochondrial fragmentation as well as adaptive IgM production in ME/CFS patients. Our findings provide mechanistic insight into both ME/CFS and long COVID development. Finding of increased circulating FN1 and depletion of (n)IgM-FN1 as a biomarker for the severity of both ME/CFS and long COVID has an immediate implication in diagnostics and development of treatment modalities.
AB - Myalgic Encephalomyelitis/ Chronic Fatigue syndrome (ME/CFS) is a complex, debilitating, long-term illness without a diagnostic biomarker. ME/CFS patients share overlapping symptoms with long COVID patients, an observation which has strengthened the infectious origin hypothesis of ME/CFS. However, the exact sequence of events leading to disease development is largely unknown for both clinical conditions. Here we show antibody response to herpesvirus dUTPases, particularly to that of Epstein-Barr virus (EBV) and HSV-1, increased circulating fibronectin (FN1) levels in serum and depletion of natural IgM against fibronectin ((n)IgM-FN1) are common factors for both severe ME/CFS and long COVID. We provide evidence for herpesvirus dUTPases-mediated alterations in host cell cytoskeleton, mitochondrial dysfunction and OXPHOS. Our data show altered active immune complexes, immunoglobulin-mediated mitochondrial fragmentation as well as adaptive IgM production in ME/CFS patients. Our findings provide mechanistic insight into both ME/CFS and long COVID development. Finding of increased circulating FN1 and depletion of (n)IgM-FN1 as a biomarker for the severity of both ME/CFS and long COVID has an immediate implication in diagnostics and development of treatment modalities.
U2 - 10.1101/2023.06.23.23291827
DO - 10.1101/2023.06.23.23291827
M3 - Preprint
C2 - 37425897
T3 - medRxiv : the preprint server for health sciences
BT - Increased circulating fibronectin, depletion of natural IgM and heightened EBV, HSV-1 reactivation in ME/CFS and long COVID
PB - medRxiv
ER -