Aicardi–Goutières syndrome harbours abundant systemic and brain-reactive autoantibodies

Objectives Aicardi–Goutieres 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 autoantibodiesin AGS. Here, we aim to profile specific autoantibodiesin AGS and to determine whether these autoantibodiestarget cerebral epitopes. Methods Using a multiplex microarray, we assessed the spectrum of serum autoantibodiesin 56 genetically confirmed patients with AGS. We investigated the presence of immunoglobulins in AGS brainspecimens 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 autoantibodiesunique from other autoimmune diseases. Some of these autoantibodiestarget endothelial cells and astrocytes in the brain of the affected patients, perhaps explaining the prominence of neurological disease in the AGS phenotype.