Abstract Details

Title Autoimmune hepatitis in Aicardi-Goutières Syndrome

Topic Child Neurology and Developmental Neurology

Presentation(s) P4 - Poster Session 4 (5:30 PM-6:30 PM)

Poster/Presentation
Number 7-045

Objective

Establish frequency of hepatic injury based on liver enzyme testing and presence of auto-antibodies in Aicardi-Goutières syndrome (AGS)

Background AGS is a genetic interferonopathy caused by mutations in IFIH1, TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, and ADAR1 associated with systemic complications affecting most organ systems. While liver injury has been reported in AGS, its incidence and severity has not yet been characterized.

Design/Methods 34 individuals with molecularly defined AGS were studied according to an IRB-approved protocol. Data collected included measurements of liver enzymes (aspartate aminotransferase [AST], alanine aminotransferase [ALT], gamma glutamyl transferase [GGT]) and autoimmune liver antibodies (anti-nuclear, anti F-actin, and anti-smooth muscle antibodies). Abnormalities were compared to a proposed biomarker of disease, interferon signaling gene expression (ISG) score, as measured by Nanostring multiplex RT PCR. Wilcoxon matched-pairs signed rank tests were performed to assess the relationship between variables.

Results A majority of individuals had abnormal ISG scores relative to normative values (n=31/34) and positive liver auto-antibodies (n=20/34). Half of the individuals in our cohort demonstrated elevations in AST, ALT, or GGT (defined as an increase more than 2 times the upper limit of normal [ULN], and in some cases as high as 22 times the ULN). There was no correlation between the presence of auto-antibodies with elevations in AST, ALT, or GGT. There was a significant correlation between the presence of abnormal ISG and abnormal AST/ALT (p=0.001) and GGT (p=0.0005). There was a significant correlation between abnormal ISG and the presence of auto-antibodies (p=0.001).

Conclusions Autoimmune hepatitis and the presence of liver-specific antibodies are a frequent finding in AGS. We found correlations between abnormal ISG scores and both abnormalities in liver enzymes and the presence of liver auto-antibodies. We hypothesize that interferon-mediated injury is the primary pathway for liver abnormalities in AGS, and that autoimmune antibodies are a secondary consequence to interferon-mediated injury.

Authors/Disclosures
Zachary Cross PRESENTER	No disclosure on file
Alyssa Kriegermeier	No disclosure on file
	No disclosure on file
	No disclosure on file
Asako Takanohashi, PhD, DVM (Children's Hospital of Philadelphia)	Dr. Takanohashi has nothing to disclose.
	No disclosure on file
Adeline Vanderver, MD, FAAN (Children'S Hospital of Philadelphia)	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.
Laura A. Adang, MD	Dr. Adang has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Orchard Therapeutics.

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