Autoantibodies against SUMO1-DHX35 in long-COVID.

Autor:	Thurner L; José Carreras Center for Immuno- and Gene Therapy and Internal Medicine I, Saarland University Medical School, Homburg/Saar, Germany., Fadle N; José Carreras Center for Immuno- and Gene Therapy and Internal Medicine I, Saarland University Medical School, Homburg/Saar, Germany., Regitz E; José Carreras Center for Immuno- and Gene Therapy and Internal Medicine I, Saarland University Medical School, Homburg/Saar, Germany., Preuss KD; José Carreras Center for Immuno- and Gene Therapy and Internal Medicine I, Saarland University Medical School, Homburg/Saar, Germany., Neumann F; José Carreras Center for Immuno- and Gene Therapy and Internal Medicine I, Saarland University Medical School, Homburg/Saar, Germany., Cetin O; José Carreras Center for Immuno- and Gene Therapy and Internal Medicine I, Saarland University Medical School, Homburg/Saar, Germany., Schormann C; José Carreras Center for Immuno- and Gene Therapy and Internal Medicine I, Saarland University Medical School, Homburg/Saar, Germany., Hoffmann MC; José Carreras Center for Immuno- and Gene Therapy and Internal Medicine I, Saarland University Medical School, Homburg/Saar, Germany., Herr C; Department of Internal Medicine V - Pulmonology, Allergology and Critical Care Medicine, Saarland University, Homburg, Germany., Kheiroddin P; University Children's Hospital Regensburg (KUNO) at the Hospital St. Hedwig of the Order of St. John, University of Regensburg, Regensburg, Germany., Rixecker TM; Department of Internal Medicine V - Pulmonology, Allergology and Critical Care Medicine, Saarland University, Homburg, Germany., Bals R; Department of Internal Medicine V - Pulmonology, Allergology and Critical Care Medicine, Saarland University, Homburg, Germany.; Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI), Saarland University Campus, 66123, Saarbrücken, Germany., Muller S; Centre National de la Recherche Scientifique-Université de Strasbourg, Unit Biotechnology and Cell Signalling, Team Neuroimmunology and Peptide Therapeutics/Strasbourg Drug Discovery and Development Institute, Strasbourg, France., Thurner B; Department of Pediatrics, Klinikum Kempten, Germany., Kessel C; Department of Pediatric Rheumatology and Immunology, University Children's Hospital Muenster, Germany., Kabesch M; University Children's Hospital Regensburg (KUNO) at the Hospital St. Hedwig of the Order of St. John, University of Regensburg, Regensburg, Germany., Bewarder M; José Carreras Center for Immuno- and Gene Therapy and Internal Medicine I, Saarland University Medical School, Homburg/Saar, Germany., Heyne K; José Carreras Center for Immuno- and Gene Therapy and Internal Medicine I, Saarland University Medical School, Homburg/Saar, Germany., Lensch C; Department of Internal Medicine V - Pulmonology, Allergology and Critical Care Medicine, Saarland University, Homburg, Germany., Kos IA; José Carreras Center for Immuno- and Gene Therapy and Internal Medicine I, Saarland University Medical School, Homburg/Saar, Germany.
Jazyk:	angličtina
Zdroj:	Journal of translational autoimmunity [J Transl Autoimmun] 2022 Nov 20; Vol. 5, pp. 100171. Date of Electronic Publication: 2022 Nov 20 (Print Publication: 2022).
DOI:	10.1016/j.jtauto.2022.100171
Abstrakt:	Long COVID is a collection of symptoms as a late sequelae of SARS-CoV-2 infection. It often includes mental symptoms such as cognitive symptoms, persisting loss of smell and taste, in addition to exertional dyspnea. A role of various autoantibodies (autoAbs) has been postulated in long-COVID and is being further investigated. With the goal of identifying potentially unknown autoAbs, we screened plasma of patients with long COVID on in-house post-translationally modified protein macroarrays including citrullinated, SUMOylated and acetylated membranes. SUMO1ylated isoform DEAD/H (Asp-Glu-Ala-Asp/His) box helicase 35 (SUMO1-DHX35) was identified as only candidate antigen. In adult patients with long COVID, IgG autoAbs against SUMO1-DHX35 of IgG class were found in seven of 71 (9.8%) plasma samples, of IgM and IgG class in one of 69 (1.4%) samples, not in 200 healthy adult controls, not in 442 healthy children, and 146 children after SARS-CoV-2 infection. All autoAb-positive seven patients were female. AutoAb titers ranged between 200 to up to 400 By point mutagenesis and expression of FLAG-tagged mutants of DHX35 in HEK293 cells, and subsequent SUMOylation of purified constructs, lysine 53 was identified as a unique, never yet identified, SUMOylation site. The autoAbs had no reactivity against the non-SUMO1ylated mutant (K53R) of DHX35. To summarize, autoAbs against SUMO1-DHX35 were identified in adult female patients with long-COVID. Further studies are needed to verify the frequency of occurrence. The function of DHX35 has not yet been determined and there is no available information in relation to disease implication. The molecular mechanism causing the SUMOylation, the potential functional consequences of this post-translational modification on DHX35, and a potential pathogenicity of the autoAbs against SUMO1-DHX35 in COVID-19 and other possible contexts remain to be elucidated. Competing Interests: LTh received travel grants from Abbvie, Janssen and EUSA-Pharm, and consultancy from Takeda, Astra-Zeneca, Merck, Incyte and EUSA-pharm (less than $10,000 each). CK has received consulting fees from 10.13039/100004336Novartis and 10.13039/501100012112Swedish Orphan Biovitrum (SOBI) (less than $10,000 each) and receives research support from 10.13039/100004336Novartis. (© 2022 Published by Elsevier B.V.)
Databáze:	MEDLINE
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