HLA class II sequence polymorphisms and susceptibility to rheumatoid arthritis in Greeks. The HLA-DR beta shared-epitope hypothesis accounts for the disease in only a minority of Greek patients.
OBJECTIVE
In Northern Europeans, rheumatoid arthritis (RA) is strongly associated with a relatively conserved pentapeptide sequence of HLA-DR beta found notably in the HLA-DR4 subtypes Dw4 and Dw14 and in DR1. A previous serologic study of HLA class II polymorphism in a Greek population with RA failed to show significant associations with any antigen.


METHODS
We characterized HLA-DRB polymorphisms in Greek patients with RA and in control subjects by restriction fragment length polymorphism analysis. Allelic DRB subtypes were examined by polymerase chain reaction amplification and oligonucleotide hybridization.


RESULTS
DNA analysis in the RA patients showed that although individual HLA-DR allelic associations were weak, a relatively conserved HLA-DR beta motif was significantly associated with RA in this population of Greek patients. The third hypervariable region amino acid sequences QRRAA, QKRAA, or RRRAA were found in the HLA-DR beta 1 of 43.5% of the RA patients versus 15.5% of the controls (uncorrected P = 0.00004).


CONCLUSIONS
Sequences shown to influence susceptibility to RA in patients in the UK also play a role in patients in Greece. However, 57% of Greek patients lack the putative HLA-DR beta motif, which suggests that considerable immunogenetic heterogeneity underlies disease susceptibility in this population.
Molecular Immunogenetics Unit, United Medical School, London, United Kingdom.
K A
KA
Boki
G S
GS
Panayi
R W
RW
Vaughan
A A
AA
Drosos
H M
HM
Moutsopoulos
J S
JS
Lanchbury
D000595:Amino Acid Sequence; D001172:Arthritis, Rheumatoid / Q000208:ethnology* / Q000276:immunology*; D004247:DNA / Q000032:analysis; D005260:Female; D005784:Gene Amplification; D006115:Greece; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D012150:Polymorphism, Restriction Fragment Length; D055503:Protein Multimerization
D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D000949:Histocompatibility Antigens Class II; D015345:Oligonucleotide Probes; D004247:DNA