Molecular genetic analysis of HLA-DR and HLA-DQ genes among anti-U1-70-kd autoantibody positive connective tissue disease patients.
OBJECTIVE
We have recently found that the presence of autoantibodies against the 70-kd polypeptide of U1 RNP (U1-70-kd) is associated with HLA-DR4 and DR2. To further characterize this association, we performed a molecular genetic analysis of HLA-DR and DQ genes among patients with autoantibodies against U1-70-kd.


METHODS
The polymerase chain reaction (PCR), sequence-specific oligonucleotide hybridization, and solid-phase direct DNA sequencing of PCR-amplified DNA were utilized to analyze HLA-DRB1, DRB5, DQA1, and DQB1 genes.


RESULTS
A comprehensive analysis of HLA-DRB1, DRB5, DQA1, and DQB1 from 27 patients and controls identified shared amino acids FDYFYQA (Phe, Asp, Tyr, Phe, Tyr, Gln, Ala) at positions 26, 28, 30-32, 70, and 73 of HLA-DRB1 on disease-associated haplotypes.


CONCLUSIONS
A common cluster of shared amino acids, or a shared epitope, identified within HLA-DRB1 among anti-U1-70-kd autoantibody positive connective tissue disease patients may be important in regulating an autoimmune response to the U1-70-kd antigen.
Department of Medicine, University of Missouri-Columbia.
H
H
Kaneoka
K C
KC
Hsu
Y
Y
Takeda
G C
GC
Sharp
R W
RW
Hoffman
D000595:Amino Acid Sequence; D001323:Autoantibodies / Q000032:analysis* / Q000276:immunology; D001483:Base Sequence; D003240:Connective Tissue Diseases / Q000097:blood / Q000235:genetics / Q000276:immunology*; D004247:DNA / Q000235:genetics; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D005260:Female; D005838:Genotype; D006683:HLA-DQ Antigens / Q000235:genetics*; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D059847:HLA-DRB5 Chains; D006239:Haplotypes; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization; D015345:Oligonucleotide Probes; D016133:Polymerase Chain Reaction; D012261:Ribonucleoproteins / Q000276:immunology*; D017411:Ribonucleoproteins, Small Nuclear; D012689:Sequence Homology, Nucleic Acid
D001323:Autoantibodies; D000939:Epitopes; D006683:HLA-DQ Antigens; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; C069050:HLA-DQA1 antigen; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D059847:HLA-DRB5 Chains; D000949:Histocompatibility Antigens Class II; D015345:Oligonucleotide Probes; D012261:Ribonucleoproteins; D017411:Ribonucleoproteins, Small Nuclear; D004247:DNA