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Extended report
Aicardi–Goutières syndrome harbours abundant systemic and brain-reactive autoantibodies
  1. Eloy Cuadrado1,2,
  2. Adeline Vanderver3,
  3. Kristy J Brown3,
  4. Annie Sandza3,
  5. Asako Takanohashi3,
  6. Machiel H Jansen2,
  7. Jasper Anink4,
  8. Brian Herron5,
  9. Simona Orcesi6,
  10. Ivana Olivieri6,
  11. Gillian I Rice7,
  12. Eleonora Aronica4,8,
  13. Pierre Lebon9,
  14. Yanick J Crow7,
  15. Elly M Hol1,8,10,
  16. Taco W Kuijpers2
  1. 1Astrocyte Biology & Neurodegeneration, Netherlands Institute for Neuroscience, an Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands
  2. 2Department of Experimental Immunology, Academic Medical Center, University of Amsterdam (UvA), Amsterdam, The Netherlands
  3. 3Center for Genetic Medicine Research, Children's National Medical Center, Washington DC, USA
  4. 4Department of (Neuro)Pathology, SEIN—Stichting Epilepsie Instellingen Nederland, Academic Medical Center, University of Amsterdam (UvA), Amsterdam, The Netherlands
  5. 5Department of Neuropathology, Royal Victoria Hospital, Belfast, UK
  6. 6Child Neurology and Psychiatry Unit, C. Mondino National Neurological Institute, Pavia, Italy
  7. 7Manchester Centre for Genomic Medicine, University of Manchester, Manchester Academic Health Sciences Centre (MAHSC), Manchester, UK
  8. 8Swammerdam Institute for Life Sciences, Center for Neuroscience, University of Amsterdam, Amsterdam, The Netherlands
  9. 9Hôpital Cochin, Université Paris Descartes, Service de Virologie, Paris, France
  10. 10Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands
  1. Correspondence to Dr Eloy Cuadrado, Astrocyte Biology & Neurodegeneration Group, Netherlands Institute for Neuroscience, Meibergdreef 47, Amsterdam 1105 BA, The Netherlands; e.cuadrado{at}, eloycua{at}


Objectives Aicardi–Goutières syndrome (AGS) is an autoimmune disorder that shares similarities with systemic lupus erythematous. AGS inflammatory responses specially target the cerebral white matter. However, it remains uncertain why the brain is the most affected organ, and little is known about the presence of autoantibodies in AGS. Here, we aim to profile specific autoantibodies in AGS and to determine whether these autoantibodies target cerebral epitopes.

Methods Using a multiplex microarray, we assessed the spectrum of serum autoantibodies in 56 genetically confirmed patients with AGS. We investigated the presence of immunoglobulins in AGS brain specimens using immunohistochemistry and studied the reactivity of sera against brain epitopes with proteomics.

Results Serum from patients exhibited high levels of IgGs against nuclear antigens (gP210, Nup62, PCNA, Ro/SSA, Sm/RNP complex, SS-A/SS-B), components of the basement membrane (entactin, laminin), fibrinogen IV and gliadin. Upon testing whether antibodies in AGS could be found in the central nervous system, IgGs were identified to target in vivo endothelial cells in vivo and astrocytes in brain sections of deceased patients with AGS. Using a proteomics approach, we were able to confirm that IgGs in serum samples from AGS patients bind epitopes present in the cerebral white matter.

Conclusions Patients with AGS produce a broad spectrum of autoantibodies unique from other autoimmune diseases. Some of these autoantibodies target endothelial cells and astrocytes in the brain of the affected patients, perhaps explaining the prominence of neurological disease in the AGS phenotype.

  • Autoantibodies
  • Autoimmune Diseases
  • Autoimmunity
  • Inflammation
  • Systemic Lupus Erythematosus

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