Polymorphism at the HLA-DQ locus determines susceptibility to experimental autoimmune myasthenia gravis

Raghavan Raju, Wen Zhi Zhan, Peter Karachunski, Bianca Conti-Fine, Gary C Sieck, Chella David

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Studies in myasthenia gravis (MG) patients demonstrate that polymorphism at the HLA-DQ locus influences the development of MG. Several studies using the mouse models also demonstrate the influence of class II molecules, especially the H2-A, which is the mouse homologue of HLA-DQ, in experimental autoimmune myasthenia gravis (EAMG). We used transgenic mice expressing two different DQ molecules, DQ8 (]DQA1*0301/B1*0302) and DQ6 (DQA1*0103/B1*0601), to evaluate the role of HLA-DQ genes in MG. These mice do not express endogenous mouse class H molecules since they contain the mutant H2-Aβ0 gene. The mice were immunized with Torpedo acetylcholine receptor, and EAMG was assessed by clinical evaluation and was confirmed by electrophysiology. Clinical scores for EAMG were highest in HLA-DQ8 transgenic mice, whereas the scores of HLA-DQ6 mice rarely exceeded grade 1. There was no incidence of EAMG in class II-deficient (H2-Aβ0) mice. These results demonstrate that polymorphism at the HLA-DQ locus affects the incidence and the severity of EAMG. The manifestation of susceptibility to EAMG in the context of human class II molecules underscores the important roles of these molecules in the initiation and perpetuation of EAMG.

Original languageEnglish (US)
Pages (from-to)4169-4174
Number of pages6
JournalJournal of Immunology
Volume160
Issue number9
StatePublished - May 1 1998

Fingerprint

Autoimmune Experimental Myasthenia Gravis
HLA-DQ Antigens
Myasthenia Gravis
Transgenic Mice
Torpedo
Electrophysiology
Incidence
Cholinergic Receptors
Genes

ASJC Scopus subject areas

  • Immunology

Cite this

Raju, R., Zhan, W. Z., Karachunski, P., Conti-Fine, B., Sieck, G. C., & David, C. (1998). Polymorphism at the HLA-DQ locus determines susceptibility to experimental autoimmune myasthenia gravis. Journal of Immunology, 160(9), 4169-4174.

Polymorphism at the HLA-DQ locus determines susceptibility to experimental autoimmune myasthenia gravis. / Raju, Raghavan; Zhan, Wen Zhi; Karachunski, Peter; Conti-Fine, Bianca; Sieck, Gary C; David, Chella.

In: Journal of Immunology, Vol. 160, No. 9, 01.05.1998, p. 4169-4174.

Research output: Contribution to journalArticle

Raju, R, Zhan, WZ, Karachunski, P, Conti-Fine, B, Sieck, GC & David, C 1998, 'Polymorphism at the HLA-DQ locus determines susceptibility to experimental autoimmune myasthenia gravis', Journal of Immunology, vol. 160, no. 9, pp. 4169-4174.
Raju R, Zhan WZ, Karachunski P, Conti-Fine B, Sieck GC, David C. Polymorphism at the HLA-DQ locus determines susceptibility to experimental autoimmune myasthenia gravis. Journal of Immunology. 1998 May 1;160(9):4169-4174.
Raju, Raghavan ; Zhan, Wen Zhi ; Karachunski, Peter ; Conti-Fine, Bianca ; Sieck, Gary C ; David, Chella. / Polymorphism at the HLA-DQ locus determines susceptibility to experimental autoimmune myasthenia gravis. In: Journal of Immunology. 1998 ; Vol. 160, No. 9. pp. 4169-4174.
@article{253da6ae39394d8c8cf54f61686de483,
title = "Polymorphism at the HLA-DQ locus determines susceptibility to experimental autoimmune myasthenia gravis",
abstract = "Studies in myasthenia gravis (MG) patients demonstrate that polymorphism at the HLA-DQ locus influences the development of MG. Several studies using the mouse models also demonstrate the influence of class II molecules, especially the H2-A, which is the mouse homologue of HLA-DQ, in experimental autoimmune myasthenia gravis (EAMG). We used transgenic mice expressing two different DQ molecules, DQ8 (]DQA1*0301/B1*0302) and DQ6 (DQA1*0103/B1*0601), to evaluate the role of HLA-DQ genes in MG. These mice do not express endogenous mouse class H molecules since they contain the mutant H2-Aβ0 gene. The mice were immunized with Torpedo acetylcholine receptor, and EAMG was assessed by clinical evaluation and was confirmed by electrophysiology. Clinical scores for EAMG were highest in HLA-DQ8 transgenic mice, whereas the scores of HLA-DQ6 mice rarely exceeded grade 1. There was no incidence of EAMG in class II-deficient (H2-Aβ0) mice. These results demonstrate that polymorphism at the HLA-DQ locus affects the incidence and the severity of EAMG. The manifestation of susceptibility to EAMG in the context of human class II molecules underscores the important roles of these molecules in the initiation and perpetuation of EAMG.",
author = "Raghavan Raju and Zhan, {Wen Zhi} and Peter Karachunski and Bianca Conti-Fine and Sieck, {Gary C} and Chella David",
year = "1998",
month = "5",
day = "1",
language = "English (US)",
volume = "160",
pages = "4169--4174",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "9",

}

TY - JOUR

T1 - Polymorphism at the HLA-DQ locus determines susceptibility to experimental autoimmune myasthenia gravis

AU - Raju, Raghavan

AU - Zhan, Wen Zhi

AU - Karachunski, Peter

AU - Conti-Fine, Bianca

AU - Sieck, Gary C

AU - David, Chella

PY - 1998/5/1

Y1 - 1998/5/1

N2 - Studies in myasthenia gravis (MG) patients demonstrate that polymorphism at the HLA-DQ locus influences the development of MG. Several studies using the mouse models also demonstrate the influence of class II molecules, especially the H2-A, which is the mouse homologue of HLA-DQ, in experimental autoimmune myasthenia gravis (EAMG). We used transgenic mice expressing two different DQ molecules, DQ8 (]DQA1*0301/B1*0302) and DQ6 (DQA1*0103/B1*0601), to evaluate the role of HLA-DQ genes in MG. These mice do not express endogenous mouse class H molecules since they contain the mutant H2-Aβ0 gene. The mice were immunized with Torpedo acetylcholine receptor, and EAMG was assessed by clinical evaluation and was confirmed by electrophysiology. Clinical scores for EAMG were highest in HLA-DQ8 transgenic mice, whereas the scores of HLA-DQ6 mice rarely exceeded grade 1. There was no incidence of EAMG in class II-deficient (H2-Aβ0) mice. These results demonstrate that polymorphism at the HLA-DQ locus affects the incidence and the severity of EAMG. The manifestation of susceptibility to EAMG in the context of human class II molecules underscores the important roles of these molecules in the initiation and perpetuation of EAMG.

AB - Studies in myasthenia gravis (MG) patients demonstrate that polymorphism at the HLA-DQ locus influences the development of MG. Several studies using the mouse models also demonstrate the influence of class II molecules, especially the H2-A, which is the mouse homologue of HLA-DQ, in experimental autoimmune myasthenia gravis (EAMG). We used transgenic mice expressing two different DQ molecules, DQ8 (]DQA1*0301/B1*0302) and DQ6 (DQA1*0103/B1*0601), to evaluate the role of HLA-DQ genes in MG. These mice do not express endogenous mouse class H molecules since they contain the mutant H2-Aβ0 gene. The mice were immunized with Torpedo acetylcholine receptor, and EAMG was assessed by clinical evaluation and was confirmed by electrophysiology. Clinical scores for EAMG were highest in HLA-DQ8 transgenic mice, whereas the scores of HLA-DQ6 mice rarely exceeded grade 1. There was no incidence of EAMG in class II-deficient (H2-Aβ0) mice. These results demonstrate that polymorphism at the HLA-DQ locus affects the incidence and the severity of EAMG. The manifestation of susceptibility to EAMG in the context of human class II molecules underscores the important roles of these molecules in the initiation and perpetuation of EAMG.

UR - http://www.scopus.com/inward/record.url?scp=0032080382&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032080382&partnerID=8YFLogxK

M3 - Article

VL - 160

SP - 4169

EP - 4174

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 9

ER -