New Insights on DR and DQ Human Leukocyte Antigens in Anti-LGI1 Encephalitis.


Journal

Neurology(R) neuroimmunology & neuroinflammation
ISSN: 2332-7812
Titre abrégé: Neurol Neuroimmunol Neuroinflamm
Pays: United States
ID NLM: 101636388

Informations de publication

Date de publication:
05 2023
Historique:
received: 16 08 2022
accepted: 26 01 2023
medline: 29 3 2023
entrez: 27 3 2023
pubmed: 28 3 2023
Statut: epublish

Résumé

To explore the clinical characteristics and HLA associations of patients with anti-leucine-rich glioma-inactivated 1 encephalitis (LGI1E) from a large single center in Israel. Anti-LGI1E is the most commonly diagnosed antibody-associated encephalitic syndrome in adults. Recent studies of various populations reveal significant associations with specific HLA genes. We examined the clinical characteristics and HLA associations of a cohort of Israeli patients. Seventeen consecutive patients with anti-LGI1E diagnosed at Tel Aviv Medical Center between the years 2011 and 2018 were included. HLA typing was performed using next-generation sequencing at the tissue typing laboratory of Sheba Medical Center and compared with data from the Ezer Mizion Bone Marrow Donor Registry, containing over 1,000,000 samples. Our cohort displayed a male predominance and median age at onset in the 7th decade, as previously reported. The most common presenting symptom was seizures. Notably, paroxysmal dizziness spells were significantly more common than previously reported (35%), whereas faciobrachial dystonic seizures were found only in 23%. HLA analysis revealed overrepresentation of DRB1*07:01 (OR: 3.18, CI: 20.9 Our cohort presents distinct immune characteristics with substantially higher overrepresentation of DRB1*04:02 and slightly lower overrepresentation of DQB1*07:01 compared with previous reports implying differences between different populations. DQ-DR interactions found in our cohort may shed additional light on the complex role of immunogenetics in the pathogenesis of anti-LGI1E, implying a possible relevance of certain DQ alleles and DR-DQ interactions.

Sections du résumé

BACKGROUND AND OBJECTIVES
To explore the clinical characteristics and HLA associations of patients with anti-leucine-rich glioma-inactivated 1 encephalitis (LGI1E) from a large single center in Israel. Anti-LGI1E is the most commonly diagnosed antibody-associated encephalitic syndrome in adults. Recent studies of various populations reveal significant associations with specific HLA genes. We examined the clinical characteristics and HLA associations of a cohort of Israeli patients.
METHODS
Seventeen consecutive patients with anti-LGI1E diagnosed at Tel Aviv Medical Center between the years 2011 and 2018 were included. HLA typing was performed using next-generation sequencing at the tissue typing laboratory of Sheba Medical Center and compared with 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 at onset in the 7th decade, as previously reported. The most common presenting symptom was seizures. Notably, paroxysmal dizziness spells were significantly more common than previously reported (35%), whereas faciobrachial dystonic seizures were found only in 23%. HLA analysis revealed overrepresentation of DRB1*07:01 (OR: 3.18, CI: 20.9
DISCUSSION
Our cohort presents distinct immune characteristics with substantially higher overrepresentation of DRB1*04:02 and slightly lower overrepresentation of DQB1*07:01 compared with previous reports implying differences between different populations. DQ-DR interactions found in our cohort may shed additional light on the complex role of immunogenetics in the pathogenesis of anti-LGI1E, implying a possible relevance of certain DQ alleles and DR-DQ interactions.

Identifiants

pubmed: 36973076
pii: 10/3/e200103
doi: 10.1212/NXI.0000000000200103
pmc: PMC10042442
pii:
doi:

Substances chimiques

HLA-DQ Antigens 0
HLA-DQ beta-Chains 0
HLA-DRB1 Chains 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

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Auteurs

Yahel Segal (Y)

From the Department of Neurology (Y.S.Y.S.N., K.R., K.A., H.K., F.F., A.G.), Tel-Aviv Medical Center; Neuroimmunology Unit (K.R., K.A., H.K.), Tel-Aviv Medical Center; Sackler Faculty of Medicine (K.A., O.A.), Tel-Aviv University; Sagol School of Neuroscience (K.A.), Tel-Aviv University; Epilepsy and EEG Unit (F.F.), Tel Aviv Medical Center; Encephalitis Center (O.A., Y.P., Y.A., A.G.), Tel-Aviv Medical Center; Department of Radiology (O.A.), Tel-Aviv Medical Center; Infectious Diseases Department (Y.P.), Tel-Aviv Medical Center; Department of Mathematics (Y.L., S.I.), Bar Ilan University, Ramat Gan; Tissue Typing Laboratory (R.L., N.S.), Sheba Medical Center, Ramat Gan; Immunology Laboratory (Y.A.), Tel Aviv Medical Center, Israel; and Department of Neurological Surgery (I.R.), University of Pittsburgh School of Medicine, PA.

Michal Nisnboym (M)

From the Department of Neurology (Y.S.Y.S.N., K.R., K.A., H.K., F.F., A.G.), Tel-Aviv Medical Center; Neuroimmunology Unit (K.R., K.A., H.K.), Tel-Aviv Medical Center; Sackler Faculty of Medicine (K.A., O.A.), Tel-Aviv University; Sagol School of Neuroscience (K.A.), Tel-Aviv University; Epilepsy and EEG Unit (F.F.), Tel Aviv Medical Center; Encephalitis Center (O.A., Y.P., Y.A., A.G.), Tel-Aviv Medical Center; Department of Radiology (O.A.), Tel-Aviv Medical Center; Infectious Diseases Department (Y.P.), Tel-Aviv Medical Center; Department of Mathematics (Y.L., S.I.), Bar Ilan University, Ramat Gan; Tissue Typing Laboratory (R.L., N.S.), Sheba Medical Center, Ramat Gan; Immunology Laboratory (Y.A.), Tel Aviv Medical Center, Israel; and Department of Neurological Surgery (I.R.), University of Pittsburgh School of Medicine, PA.

Keren Regev (K)

From the Department of Neurology (Y.S.Y.S.N., K.R., K.A., H.K., F.F., A.G.), Tel-Aviv Medical Center; Neuroimmunology Unit (K.R., K.A., H.K.), Tel-Aviv Medical Center; Sackler Faculty of Medicine (K.A., O.A.), Tel-Aviv University; Sagol School of Neuroscience (K.A.), Tel-Aviv University; Epilepsy and EEG Unit (F.F.), Tel Aviv Medical Center; Encephalitis Center (O.A., Y.P., Y.A., A.G.), Tel-Aviv Medical Center; Department of Radiology (O.A.), Tel-Aviv Medical Center; Infectious Diseases Department (Y.P.), Tel-Aviv Medical Center; Department of Mathematics (Y.L., S.I.), Bar Ilan University, Ramat Gan; Tissue Typing Laboratory (R.L., N.S.), Sheba Medical Center, Ramat Gan; Immunology Laboratory (Y.A.), Tel Aviv Medical Center, Israel; and Department of Neurological Surgery (I.R.), University of Pittsburgh School of Medicine, PA.

Karni Arnon (K)

From the Department of Neurology (Y.S.Y.S.N., K.R., K.A., H.K., F.F., A.G.), Tel-Aviv Medical Center; Neuroimmunology Unit (K.R., K.A., H.K.), Tel-Aviv Medical Center; Sackler Faculty of Medicine (K.A., O.A.), Tel-Aviv University; Sagol School of Neuroscience (K.A.), Tel-Aviv University; Epilepsy and EEG Unit (F.F.), Tel Aviv Medical Center; Encephalitis Center (O.A., Y.P., Y.A., A.G.), Tel-Aviv Medical Center; Department of Radiology (O.A.), Tel-Aviv Medical Center; Infectious Diseases Department (Y.P.), Tel-Aviv Medical Center; Department of Mathematics (Y.L., S.I.), Bar Ilan University, Ramat Gan; Tissue Typing Laboratory (R.L., N.S.), Sheba Medical Center, Ramat Gan; Immunology Laboratory (Y.A.), Tel Aviv Medical Center, Israel; and Department of Neurological Surgery (I.R.), University of Pittsburgh School of Medicine, PA.

Hadar Kolb (H)

From the Department of Neurology (Y.S.Y.S.N., K.R., K.A., H.K., F.F., A.G.), Tel-Aviv Medical Center; Neuroimmunology Unit (K.R., K.A., H.K.), Tel-Aviv Medical Center; Sackler Faculty of Medicine (K.A., O.A.), Tel-Aviv University; Sagol School of Neuroscience (K.A.), Tel-Aviv University; Epilepsy and EEG Unit (F.F.), Tel Aviv Medical Center; Encephalitis Center (O.A., Y.P., Y.A., A.G.), Tel-Aviv Medical Center; Department of Radiology (O.A.), Tel-Aviv Medical Center; Infectious Diseases Department (Y.P.), Tel-Aviv Medical Center; Department of Mathematics (Y.L., S.I.), Bar Ilan University, Ramat Gan; Tissue Typing Laboratory (R.L., N.S.), Sheba Medical Center, Ramat Gan; Immunology Laboratory (Y.A.), Tel Aviv Medical Center, Israel; and Department of Neurological Surgery (I.R.), University of Pittsburgh School of Medicine, PA.

Firas Fahoum (F)

From the Department of Neurology (Y.S.Y.S.N., K.R., K.A., H.K., F.F., A.G.), Tel-Aviv Medical Center; Neuroimmunology Unit (K.R., K.A., H.K.), Tel-Aviv Medical Center; Sackler Faculty of Medicine (K.A., O.A.), Tel-Aviv University; Sagol School of Neuroscience (K.A.), Tel-Aviv University; Epilepsy and EEG Unit (F.F.), Tel Aviv Medical Center; Encephalitis Center (O.A., Y.P., Y.A., A.G.), Tel-Aviv Medical Center; Department of Radiology (O.A.), Tel-Aviv Medical Center; Infectious Diseases Department (Y.P.), Tel-Aviv Medical Center; Department of Mathematics (Y.L., S.I.), Bar Ilan University, Ramat Gan; Tissue Typing Laboratory (R.L., N.S.), Sheba Medical Center, Ramat Gan; Immunology Laboratory (Y.A.), Tel Aviv Medical Center, Israel; and Department of Neurological Surgery (I.R.), University of Pittsburgh School of Medicine, PA.

Orna Aizenstein (O)

From the Department of Neurology (Y.S.Y.S.N., K.R., K.A., H.K., F.F., A.G.), Tel-Aviv Medical Center; Neuroimmunology Unit (K.R., K.A., H.K.), Tel-Aviv Medical Center; Sackler Faculty of Medicine (K.A., O.A.), Tel-Aviv University; Sagol School of Neuroscience (K.A.), Tel-Aviv University; Epilepsy and EEG Unit (F.F.), Tel Aviv Medical Center; Encephalitis Center (O.A., Y.P., Y.A., A.G.), Tel-Aviv Medical Center; Department of Radiology (O.A.), Tel-Aviv Medical Center; Infectious Diseases Department (Y.P.), Tel-Aviv Medical Center; Department of Mathematics (Y.L., S.I.), Bar Ilan University, Ramat Gan; Tissue Typing Laboratory (R.L., N.S.), Sheba Medical Center, Ramat Gan; Immunology Laboratory (Y.A.), Tel Aviv Medical Center, Israel; and Department of Neurological Surgery (I.R.), University of Pittsburgh School of Medicine, PA.

Yael Paran (Y)

From the Department of Neurology (Y.S.Y.S.N., K.R., K.A., H.K., F.F., A.G.), Tel-Aviv Medical Center; Neuroimmunology Unit (K.R., K.A., H.K.), Tel-Aviv Medical Center; Sackler Faculty of Medicine (K.A., O.A.), Tel-Aviv University; Sagol School of Neuroscience (K.A.), Tel-Aviv University; Epilepsy and EEG Unit (F.F.), Tel Aviv Medical Center; Encephalitis Center (O.A., Y.P., Y.A., A.G.), Tel-Aviv Medical Center; Department of Radiology (O.A.), Tel-Aviv Medical Center; Infectious Diseases Department (Y.P.), Tel-Aviv Medical Center; Department of Mathematics (Y.L., S.I.), Bar Ilan University, Ramat Gan; Tissue Typing Laboratory (R.L., N.S.), Sheba Medical Center, Ramat Gan; Immunology Laboratory (Y.A.), Tel Aviv Medical Center, Israel; and Department of Neurological Surgery (I.R.), University of Pittsburgh School of Medicine, PA.

Yoram Louzoun (Y)

From the Department of Neurology (Y.S.Y.S.N., K.R., K.A., H.K., F.F., A.G.), Tel-Aviv Medical Center; Neuroimmunology Unit (K.R., K.A., H.K.), Tel-Aviv Medical Center; Sackler Faculty of Medicine (K.A., O.A.), Tel-Aviv University; Sagol School of Neuroscience (K.A.), Tel-Aviv University; Epilepsy and EEG Unit (F.F.), Tel Aviv Medical Center; Encephalitis Center (O.A., Y.P., Y.A., A.G.), Tel-Aviv Medical Center; Department of Radiology (O.A.), Tel-Aviv Medical Center; Infectious Diseases Department (Y.P.), Tel-Aviv Medical Center; Department of Mathematics (Y.L., S.I.), Bar Ilan University, Ramat Gan; Tissue Typing Laboratory (R.L., N.S.), Sheba Medical Center, Ramat Gan; Immunology Laboratory (Y.A.), Tel Aviv Medical Center, Israel; and Department of Neurological Surgery (I.R.), University of Pittsburgh School of Medicine, PA.

Sapir Israeli (S)

From the Department of Neurology (Y.S.Y.S.N., K.R., K.A., H.K., F.F., A.G.), Tel-Aviv Medical Center; Neuroimmunology Unit (K.R., K.A., H.K.), Tel-Aviv Medical Center; Sackler Faculty of Medicine (K.A., O.A.), Tel-Aviv University; Sagol School of Neuroscience (K.A.), Tel-Aviv University; Epilepsy and EEG Unit (F.F.), Tel Aviv Medical Center; Encephalitis Center (O.A., Y.P., Y.A., A.G.), Tel-Aviv Medical Center; Department of Radiology (O.A.), Tel-Aviv Medical Center; Infectious Diseases Department (Y.P.), Tel-Aviv Medical Center; Department of Mathematics (Y.L., S.I.), Bar Ilan University, Ramat Gan; Tissue Typing Laboratory (R.L., N.S.), Sheba Medical Center, Ramat Gan; Immunology Laboratory (Y.A.), Tel Aviv Medical Center, Israel; and Department of Neurological Surgery (I.R.), University of Pittsburgh School of Medicine, PA.

Ron Loewenthal (R)

From the Department of Neurology (Y.S.Y.S.N., K.R., K.A., H.K., F.F., A.G.), Tel-Aviv Medical Center; Neuroimmunology Unit (K.R., K.A., H.K.), Tel-Aviv Medical Center; Sackler Faculty of Medicine (K.A., O.A.), Tel-Aviv University; Sagol School of Neuroscience (K.A.), Tel-Aviv University; Epilepsy and EEG Unit (F.F.), Tel Aviv Medical Center; Encephalitis Center (O.A., Y.P., Y.A., A.G.), Tel-Aviv Medical Center; Department of Radiology (O.A.), Tel-Aviv Medical Center; Infectious Diseases Department (Y.P.), Tel-Aviv Medical Center; Department of Mathematics (Y.L., S.I.), Bar Ilan University, Ramat Gan; Tissue Typing Laboratory (R.L., N.S.), Sheba Medical Center, Ramat Gan; Immunology Laboratory (Y.A.), Tel Aviv Medical Center, Israel; and Department of Neurological Surgery (I.R.), University of Pittsburgh School of Medicine, PA.

Nina Svetlitzky (N)

From the Department of Neurology (Y.S.Y.S.N., K.R., K.A., H.K., F.F., A.G.), Tel-Aviv Medical Center; Neuroimmunology Unit (K.R., K.A., H.K.), Tel-Aviv Medical Center; Sackler Faculty of Medicine (K.A., O.A.), Tel-Aviv University; Sagol School of Neuroscience (K.A.), Tel-Aviv University; Epilepsy and EEG Unit (F.F.), Tel Aviv Medical Center; Encephalitis Center (O.A., Y.P., Y.A., A.G.), Tel-Aviv Medical Center; Department of Radiology (O.A.), Tel-Aviv Medical Center; Infectious Diseases Department (Y.P.), Tel-Aviv Medical Center; Department of Mathematics (Y.L., S.I.), Bar Ilan University, Ramat Gan; Tissue Typing Laboratory (R.L., N.S.), Sheba Medical Center, Ramat Gan; Immunology Laboratory (Y.A.), Tel Aviv Medical Center, Israel; and Department of Neurological Surgery (I.R.), University of Pittsburgh School of Medicine, PA.

Yifat Alcalay (Y)

From the Department of Neurology (Y.S.Y.S.N., K.R., K.A., H.K., F.F., A.G.), Tel-Aviv Medical Center; Neuroimmunology Unit (K.R., K.A., H.K.), Tel-Aviv Medical Center; Sackler Faculty of Medicine (K.A., O.A.), Tel-Aviv University; Sagol School of Neuroscience (K.A.), Tel-Aviv University; Epilepsy and EEG Unit (F.F.), Tel Aviv Medical Center; Encephalitis Center (O.A., Y.P., Y.A., A.G.), Tel-Aviv Medical Center; Department of Radiology (O.A.), Tel-Aviv Medical Center; Infectious Diseases Department (Y.P.), Tel-Aviv Medical Center; Department of Mathematics (Y.L., S.I.), Bar Ilan University, Ramat Gan; Tissue Typing Laboratory (R.L., N.S.), Sheba Medical Center, Ramat Gan; Immunology Laboratory (Y.A.), Tel Aviv Medical Center, Israel; and Department of Neurological Surgery (I.R.), University of Pittsburgh School of Medicine, PA.

Itay Raphael (I)

From the Department of Neurology (Y.S.Y.S.N., K.R., K.A., H.K., F.F., A.G.), Tel-Aviv Medical Center; Neuroimmunology Unit (K.R., K.A., H.K.), Tel-Aviv Medical Center; Sackler Faculty of Medicine (K.A., O.A.), Tel-Aviv University; Sagol School of Neuroscience (K.A.), Tel-Aviv University; Epilepsy and EEG Unit (F.F.), Tel Aviv Medical Center; Encephalitis Center (O.A., Y.P., Y.A., A.G.), Tel-Aviv Medical Center; Department of Radiology (O.A.), Tel-Aviv Medical Center; Infectious Diseases Department (Y.P.), Tel-Aviv Medical Center; Department of Mathematics (Y.L., S.I.), Bar Ilan University, Ramat Gan; Tissue Typing Laboratory (R.L., N.S.), Sheba Medical Center, Ramat Gan; Immunology Laboratory (Y.A.), Tel Aviv Medical Center, Israel; and Department of Neurological Surgery (I.R.), University of Pittsburgh School of Medicine, PA.

Avi Gadoth (A)

From the Department of Neurology (Y.S.Y.S.N., K.R., K.A., H.K., F.F., A.G.), Tel-Aviv Medical Center; Neuroimmunology Unit (K.R., K.A., H.K.), Tel-Aviv Medical Center; Sackler Faculty of Medicine (K.A., O.A.), Tel-Aviv University; Sagol School of Neuroscience (K.A.), Tel-Aviv University; Epilepsy and EEG Unit (F.F.), Tel Aviv Medical Center; Encephalitis Center (O.A., Y.P., Y.A., A.G.), Tel-Aviv Medical Center; Department of Radiology (O.A.), Tel-Aviv Medical Center; Infectious Diseases Department (Y.P.), Tel-Aviv Medical Center; Department of Mathematics (Y.L., S.I.), Bar Ilan University, Ramat Gan; Tissue Typing Laboratory (R.L., N.S.), Sheba Medical Center, Ramat Gan; Immunology Laboratory (Y.A.), Tel Aviv Medical Center, Israel; and Department of Neurological Surgery (I.R.), University of Pittsburgh School of Medicine, PA. avig@tlvmc.gov.il.

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