Identification by genomic typing of non-DR3 HLA class II genes associated with myasthenia gravis.
HLA association with myasthenia gravis (MG) has been studied in a series of 114 patients using class I and class II genotyping after PCR amplification. Positive association was found with DR3, particularly in women (RR = 2.6) and in early MG onset (RR = 3.4). DRB1, DRB3, DQB1, DQA1 and B (B8 and B18) genotyping revealed that the association was predominantly with the B8 DRB1*03 DRB3*0101 DQB1*0201 DQA1*0501 ancestral haplotype. This haplotype frequency was also increased in patients with thymic hyperplasia (RR = 3.5) and was greatly reduced in patients with thymoma (RR = 0.35). Sixteen out of 48 patients carrying this 8.1 ancestral haplotype showed absence of B8 (n = 4) or of DR3 (n = 12). HLA class II genotyping further revealed the existence of two other significant associations. MG was positively associated with the DQB1*0604 allele (RR = 3.4), particularly in patients with thymoma (RR = 5.7). Furthermore, the disease was negatively associated with DR1 in females (RR = 0.32). These data suggest that MG is placed under the control of at least three distinct genes: (1) a class II predisposing gene in the 8.1 ancestral haplotype; (2) a thymoma-associated class II allele on the DQB1*0604 haplotype; and (3) a protective allele DR1.
Inserm U25, Hôpital Necker, Paris, France.
M L
ML
Vieira
S
S
Caillat-Zucman
P
P
Gajdos
S
S
Cohen-Kaminsky
A
A
Casteur
J F
JF
Bach
D000367:Age Factors; D001323:Autoantibodies / Q000032:analysis; D001483:Base Sequence; D005260:Female; D005787:Gene Frequency; D005802:Genes, MHC Class II; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009157:Myasthenia Gravis / Q000145:classification / Q000235:genetics* / Q000276:immunology; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D011978:Receptors, Nicotinic / Q000276:immunology; D013950:Thymus Gland / Q000473:pathology; D044465:White People
D001323:Autoantibodies; D009838:Oligodeoxyribonucleotides; D011978:Receptors, Nicotinic