Susceptibility to ankylosing spondylitis is independent of the Bw4 and Bw6 epitopes of HLA-B27 alleles.
We have characterized HLA-B27 alleles in a sample of the population from the Azores (n=46) with the aim of investigating the contribution of different subtypes to ankylosing spondylitis (AS). The study was carried out using PCR-SSOP and in some samples genomic sequencing was conducted. Some significant new finding have arisen from this study. First, B*2705,B*2702,B*2703,B*2707 and B*2708 alleles were found to be represented in this population. The polymorphism of B27 alleles found in a sample of the population from the Azores is higher than the Caucasian groups described. B*2703 and B*2707 have not previously been described to be represented in Caucasians and this could indicate admixtures with different populations of the world. In addition, the B*2708 allele was found to be associated with AS in a large family from the Azores. This association has not been previously reported in either ethnic group and needs to be confirmed in other population studies. This is of considerable interest since has only been described as a rare subtype underrepresented in the British population and has not been previously found to be associated with AS. B*2708 carries the sequence specifying the Bw6 epitope in contrast to most B27 alleles which carry a Bw4 sequence. Differences in this region (residues 77-83) can alter the F-pocket and affect T-cell recognition. The importance that these molecular changes can play in the pathogenesis of AS is discussed.
Armas
J B
JB
Internal Medicine Department, Hospital de Santo Espirito de Angra do Heroismo, Azores, Portugal.
Gonzalez
S
S
Martinez-Borra
J
J
Laranjeira
F
F
Ribeiro
E
E
Correia
J
J
Ferreira
M L
ML
Toste
M
M
López-Vazquez
A
A
López-Larrea
C
C
D001394:Azores; D044383:Black People / Q000235:genetics; D004198:Disease Susceptibility / Q000276:immunology; D018604:Epitope Mapping; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D015235:HLA-B Antigens / Q000235:genetics / Q000276:immunology; D015796:HLA-B27 Antigen / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D010375:Pedigree; D013167:Spondylitis, Ankylosing / Q000235:genetics* / Q000276:immunology*; D044465:White People / Q000235:genetics
D015235:HLA-B Antigens; D015796:HLA-B27 Antigen; C042388:HLA-Bw4 antigen; C038652:HLA-Bw6 antigen