Autoimmunogenic HLA-DRB1*0301 allele (DR3) may be distinguished at the DRB1 non-coding regions of HLA-B8,DR3,Dw24 and B18,DR3,Dw25 haplotypes.
A novel TaqI restriction fragment length polymorphism (RFLP) of 4.15 kb is reported using a DR beta probe (pRTV1). This fragment corresponds to the DRB1 locus and allows the subdivision at the DNA level of the DRB1*0301 allele (DR3 antigen), which had not previously been reported. Both splits also distinguish each of the two DR3-bearing extended haplotypes (HLA-B8,SCO1,DR3,DQw2,Dw24 and B18,F1C30,DR3,DQw2,Dw25) found associated to several autoimmune diseases as insulin-dependent diabetes mellitus (IDDM), systemic lupus erythematosus (SLE) and myasthenia gravis. The fact that no polymorphism in the DRB1*0301 coding DNA sequence has been detected indicates that DRB1*0301 intronic, regulatory of neighbouring sequences might also contribute to differential disease associations (and pathogenic mechanisms) found linked to each of the two DR3-bearing haplotypes, i.e. IDDM and B8,DR3,Dw24 in North European/American Caucasoids vs IDDM and B18,DR3,Dw25 in Mediterraneans; SLE and B8,DR3,Dw24 in children vs SLE and B18,DR3,Dw25 in Spanish adults.
Segurado
O G
OG
Department of Immunology, Hospital 12 de Octubre, Madrid, Spain.
Iglesias-Casarrubios
P
P
Martinez-Laso
J
J
Corell
A
A
Martin-Villa
J M
JM
Arnaiz-Villena
A
A
D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology; D015803:HLA-DR3 Antigen / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D010375:Pedigree; D012150:Polymorphism, Restriction Fragment Length
D015803:HLA-DR3 Antigen