Abstract Details

Title Expanding Our Knowledge Of The Immunogenetic Characteristics Of Anti-LGI1 Encephalitis – A Study Of An Israeli Cohort Suggests Additional Significant HLA Associations With DQ Alleles

Topic Autoimmune Neurology

Presentation(s) C8 - Approach to Autoimmune Encephalitis/Epilepsy 2 (11:25 AM-11:30 AM)
P2 - Poster Session 2 (9:00 AM-3:00 PM)

Poster/Presentation
Number 032

Background

Anti-LGI1E is one of the most commonly diagnosed antibody-associated encephalitic syndromes in adults. Recent studies of various populations reveal significant associations with specific Human Leukocyte Antigen (HLA) genes. We examined the clinical characteristics and HLA associations of a cohort of Israeli patients.

Objective

Exploring the clinical characteristics and HLA associations of patients with anti-leucine–rich glioma-inactivated 1 encephalitis (LGI1E) from a large single center in Israel

Design/Methods

Seventeen consecutive anti-LGI1E patients diagnosed at Tel Aviv Sourasky Medical Center between the years 2011-2018 were included. HLA typing was performed using NGS methodology at the tissue typing laboratory of Sheba Medical Center and compared to data from the "Ezer Mizion" Bone Marrow Donor Registry, containing over 1,000,000 samples.

Results

Our cohort displayed a male predominance and median age of onset in the 7th decade, as previously reported. All patients responded to immunotherapy, though residual damage was not uncommon (23% with MRS>1).

HLA analysis revealed overexpression of DRB1*07:01 (OR 13, CI 0.6 p<1.e-10) and DRB1*04:02 (OR 12, CI-0.6 p<1.e-10), as previously reported, as well as of the DQ alleles DQB1*02:02 (OR 12, CI 0.6p<1.e-10), DQB1*03:03 (OR 27, CI 0.9 p<1.e-10), previously attributed to linkage disequilibrium (LD) with the mentioned DR alleles. An additional allele overexpressed among our patients was the DQB1*03:02 allele (OR 12, CI 0.6 p<1.e-10), which appeared in complete LD with DRB1*04:02. Linkage disequilibrium analysis performed on patients and controls suggests these DR-DQ associations are unique to anti-LGI1E patients. In silico predictions performed for the overexpressed DQ alleles reveal them to be strong binders of LGI1 derived peptides, and suggest a correlation between peptide binding sites of paired DR-DQ alleles.

Conclusions

Our findings shed additional light on the complex role of immunogenetics in the pathogenesis of anti-LGI1E, implying the possible relevance of certain DQ alleles as well as DR-DQ interactions.

Authors/Disclosures
Yahel Segal, MD (Mayo Clinic) PRESENTER	Dr. Segal has nothing to disclose.
	No disclosure on file
Keren Regev, MD	Dr. Regev has nothing to disclose.
Arnon Karni, MD, PhD (Tel Aviv Sourasky medical center)	Prof. Karni has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Neopharm. Prof. Karni has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for BMS. Prof. Karni has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Prof. Karni has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. The institution of Prof. Karni has received research support from Medison. The institution of Prof. Karni has received research support from BMS. The institution of Prof. Karni has received research support from Novartis.
Hadar Kolb	Hadar Kolb has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Hadar Kolb has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Marck.
	No disclosure on file
Orna Aizenstein Lehavi	No disclosure on file
Yael Paran (Ichilov)	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Yifat Alcalay (Tel Aviv Medical Center)	Yifat Alcalay has nothing to disclose.
Avi Gadoth, MD (Tel-Aviv Medical Center)	Dr. Gadoth has received intellectual property interests from a discovery or technology relating to health care.

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