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Defective peripheral B cell selection in common variable immune deficiency patients with autoimmune manifestations

Friman, Vanda, 1952 (författare)
Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för infektionssjukdomar,Institute of Biomedicine, Department of Infectious Medicine
Quinti, Isabella (författare)
Department of Molecular Medicine, Sapienza University of Rome, Italy
Davydov, Alexey N. (författare)
Central European Institute of Technology, Brno, Czech Republic
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Shugay, Mikhail (författare)
Center of Life Sciences, Skolkovo Institute of Science and Technology, Moscow, Russian Federation ; Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russian Federation ; Institute of Translational Medicine, Pirogov Russian National Research Medical University, Moscow, Russian Federation
Farroni, Chiara (författare)
Translational Research Unit, National Institute for Infectious Diseases Lazzaro Spallanzani (IRCCS), Rome, Italy ; B Cell Pathophysiology Unit, Immunology Research Area, Ospedale Pediatrico Bambino Gesù, IRCCS, Rome, Italy
Engström, Erik (författare)
Department of Rheumatology and Inflammation Research, The Sahlgrenska Academy, University of Gothenburg, Sweden
Pour Akaber, Shirin (författare)
Institute of Pathophysiology and Allergy Research, Centre for Pathophysiology, Infectiology, and Immunology, Medical University of Vienna, Austria
Barresi, Sabina (författare)
Genetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù IRCCS, Rome, Italy
Mohamed, Ahmed (författare)
Department of Rheumatology and Inflammation Research, The Sahlgrenska Academy, University of Gothenburg, Sweden ; Faculty of Health Sciences, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland
Pulvirenti, Federica (författare)
Centre for Primary Immune Deficiency, AUO Policlinico Umberto I, Rome, Italy
Milito, Cinzia (författare)
Department of Molecular Medicine, Sapienza University of Rome, Italy
Granata, Guido (författare)
Clinical and Research Department for Infectious Diseases, National Institute for Infectious Diseases L. Spallanzani (IRCCS), Rome, Italy
Giorda, Ezio (författare)
Research Laboratories, Ospedale Pediatrico Bambino Gesù, IRCCS, Rome, Italy
Ahlström, Sara (författare)
Department of Infectious Diseases, Institute of Biomedicine, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
Karlsson, Johanna (författare)
Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för infektionssjukdomar,Institute of Biomedicine, Department of Infectious Medicine
Marasco, Emiliano (författare)
Division of Rheumatology, Ospedale Pediatrico Bambino Gesù, IRCCS, Rome, Italy
Marcellini, Valentina (författare)
Research Laboratories, Ospedale Pediatrico Bambino Gesù, IRCCS, Rome, Italy
Bocci, Chiara (författare)
B Cell Pathophysiology Unit, Immunology Research Area, Ospedale Pediatrico Bambino Gesù, IRCCS, Rome, Italy
Cascioli, Simona (författare)
Research Laboratories, Ospedale Pediatrico Bambino Gesù, IRCCS, Rome, Italy
Scarsella, Marco (författare)
Research Laboratories, Ospedale Pediatrico Bambino Gesù, IRCCS, Rome, Italy
Phad, Ganesh (författare)
Institute for Research in Biomedicine (IRB), Università della Svizzera Italiana (USI), Bellinzona, Switzerland
Tilevik, Andreas (författare)
Högskolan i Skövde,Institutionen för biovetenskap,Forskningsmiljön Systembiologi,Infektionsbiologi, Infection Biology
Tartaglia, Marco (författare)
Genetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù IRCCS, Rome, Italy
Bemark, Mats, 1967 (författare)
Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för mikrobiologi och immunologi,Institute of Biomedicine, Department of Microbiology and Immunology
Chudakov, Dmitriy M. (författare)
Center of Life Sciences, Skolkovo Institute of Science and Technology, Moscow, Russian Federation ; Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russian Federation ; Institute of Translational Medicine, Pirogov Russian National Research Medical University, Moscow, Russian Federation ; Central European Institute of Technology, Brno, Czech Republic
Carsetti, Rita (författare)
B Cell Pathophysiology Unit, Immunology Research Area, Ospedale Pediatrico Bambino Gesù, IRCCS, Rome, Italy ; Unit of Diagnostic Immunology, Department of Laboratories, Ospedale Pediatrico Bambino Gesù, IRCCS, Rome, Italy
Grimsholm, Ola, 1979 (författare)
Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research
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 (creator_code:org_t)
Elsevier, 2023
2023
Engelska.
Ingår i: Cell Reports. - : Elsevier. - 2211-1247. ; 42:5
Relaterad länk:
https://doi.org/10.1...
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https://his.diva-por... (primary) (Raw object)
https://urn.kb.se/re...
https://doi.org/10.1...
https://gup.ub.gu.se...
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  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
Stäng  
  • Common variable immune deficiency (CVID) is a heterogeneous disorder characterized by recurrent infections, low levels of serum immunoglobulins, and impaired vaccine responses. Autoimmune manifestations are common, but B cell central and peripheral selection mechanisms in CVID are incompletely understood. Here, we find that receptor editing, a measure of central tolerance, is increased in transitional B cells from CVID patients and that these cells have a higher immunoglobulin κ:λ ratio in CVID patients with autoimmune manifestations than in those with infection only. Contrariwise, the selection pressure in the germinal center on CD27bright memory B cells is decreased in CVID patients with autoimmune manifestations. Finally, functionally, T cell-dependent activation showed that naive B cells in CVID patients are badly equipped for activation and induction of mismatch repair genes. We conclude that central tolerance is functional whereas peripheral selection is defective in CVID patients with autoimmune manifestations, which could underpin the development of autoimmunity. 

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Immunology in the medical area (hsv//eng)
NATURVETENSKAP  -- Biologi -- Immunologi (hsv//swe)
NATURAL SCIENCES  -- Biological Sciences -- Immunology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Reumatologi och inflammation (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Rheumatology and Autoimmunity (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Infektionsmedicin (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Infectious Medicine (hsv//eng)

Nyckelord

CD27<sup>bright</sup> memory B cells
common variable immunodeficiency
CP: Immunology
immunoglobulin sequencing
naive B cells
peripheral B cell selection
receptor editing
transcriptomic analysis
Infection Biology
Infektionsbiologi
B cell development
CVID
central tolerance
receptor editing
antibody genes
somatic hypermutation
missmatch repair

Publikations- och innehållstyp

ref (ämneskategori)
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