Abstract Details

Title CNS Reactive Autoantibodies in Aicardi Goutieres Syndrome: Autoimmunity in a Genetic Disease

Topic Child Neurology/Developmental Neurobiology

Presentation(s) IN9 - (-)

Poster/Presentation
Number 007

Objective

Background AGS is a disorder caused by mutations in genes (SAMHD1, TREX1, ADAR1, RNASEH2A, RNASEH2B, RNASEH2C) that are thought to lead to the accumulation of immunostimulatory DNA. This triggers a type I interferon mediated inflammatory response, resulting in central nervous system injury, including intracranial calcification and leukodystrophy. While non-specific autoantibodies have been described in AGS, it is unknown if CNS-specific autoantibodies are seen in this disease.

Design/Methods Plasma samples from eight subjects with AGS and eight age-matched subjects with non-AGS leukodystrophies were compared using antigen microarrays containing 420 antigens including CNS-related autoantigens, lipids, virus-derived antigens and other autoantigens. IgG and IgM antibody to each antigen in the array was measured, and autoantibody reactivity was considered to be significant when p values were <0.05.

Results Patients with AGS had a statistically significant elevation in autoantibodies to a series of peptides from Oligodendrocyte specific protein, Aquaporin 4 receptor and Proteolipid proteins (range p=0.002-0.048). Other proteins, including myelin basic protein, heat shock proteins and GFAP, did not show a consistently elevated autoantibody response against multiple peptides.

Conclusions While these results need to be validated in a larger sample size, these results suggest that AGS patients harbor CNS-reactive autoantibodies. The pathogenicity of these autoantibodies, as well as the mechanisms leading to their generation, remains to be explored. However, this genetic disorder of the innate immune system may be an example of the overlap between acquired and genetic immune mediated disorders of the CNS.

Authors/Disclosures
Adeline Vanderver, MD, FAAN (Children'S Hospital of Philadelphia) PRESENTER	An immediate family member of Dr. Vanderver has received personal compensation for serving as an employee of Maryland Physician Care. The institution of Dr. Vanderver has received research support from Takeda. The institution of Dr. Vanderver has received research support from Passage Bio. The institution of Dr. Vanderver has received research support from Homology. The institution of Dr. Vanderver has received research support from Eli Lilly. The institution of Dr. Vanderver has received research support from Myrtelle. The institution of Dr. Vanderver has received research support from SynaptixBio. The institution of Dr. Vanderver has received research support from PMD Foundation. The institution of Dr. Vanderver has received research support from Ionis. The institution of Dr. Vanderver has received research support from ISD . The institution of Dr. Vanderver has received research support from Boehringer-Ingelheim. The institution of Dr. Vanderver has received research support from Biogen. The institution of Dr. Vanderver has received research support from Sana. The institution of Dr. Vanderver has received research support from Affinia. The institution of Dr. Vanderver has received research support from BridgeBio. The institution of Dr. Vanderver has received research support from Orchard. The institution of Dr. Vanderver has received research support from Minoryx. The institution of Dr. Vanderver has received research support from Forge Biologics. The institution of Dr. Vanderver has received research support from Vigil. Dr. Vanderver has received intellectual property interests from a discovery or technology relating to health care. Dr. Vanderver has received intellectual property interests from a discovery or technology relating to health care.
Asako Takanohashi, PhD, DVM (Children's Hospital of Philadelphia)	Dr. Takanohashi has nothing to disclose.
	No disclosure on file
	No disclosure on file
Francisco J. Quintana, PhD (Brigham and Women's Hospital/Harvard Medical)	Dr. Quintana has nothing to disclose.
	No disclosure on file

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