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Influence of the HLA-DR
shared epitope on susceptibility to
and clinical expression of rheumatoid arthritis in Chilean patients
a Departamento de Inmunología
Clínica y Reumatología, Facultad de Medicina , b Departamento de Radiología , c Departamento de Biología Celular y Molecular, Facultad
de Ciencias Biológicas , d Pontificia Universidad Católica de Chile,
Santiago, Chile Molecular Immunogenetics Unit,
Division of Medicine, UMDS, Guy's Hospital, London
Correspondence to: Dr A González, Departamento de Inmunología Clínica y Reumatología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Casilla 114-D, Santiago, Chile.
Accepted for publication 8 January 1997
OBJECTIVE
To analyse the influence of shared
epitope positive HLA-DRB1 alleles (QKRAA or QRRAA) ) on rheumatoid
arthritis (RA) susceptibility and severity in Chileans, a population
that exhibits a weak association with HLA-DR4.
METHODSPrevalence of alleles DRB1*01 and
DRB1*04 alleles was determined by polymerase chain reaction
amplification and sequence specific oligonucleotide hybridisation in
129 RA patients with defined clinical features and in 97 healthy controls.
RESULTSThe shared epitope was found in 70 (54%) of the RA patients and in 29 (30%) of controls (odds ratio (OR)
=3; 95% confidence intervals (CI) = 1.5, 5.1; p = 0.0004), and was
present in a double dose in 20% of patients versus 4% of controls (OR = 6; 95% CI = 2, 21; p = 0.0009). HLA-DRB1*0403 was the most prevalent
DR4 subtype in controls (19%). HLA-DRB1*0404 or *0408 were the alleles most prominently associated with RA, 19% versus 6 % in controls (OR=3; 95% CI = 1.3, 10; p = 0.01). The risk of RA in those carrying a
double dose of the shared epitope was 7.5 times that seen in patients
lacking the epitope. Disease severity was moderate: 33% had
extra-articular manifestations. The double dose was associated with an
increased risk of vasculitis or extra-articular manifestations. However, 59 patients (46%) did not carry the shared epitope and 18 of
them (31%) had extra-articular manifestations.
CONCLUSIONSThe weak association of RA with DR4
in Chileans seems to relate to a relatively high frequency of the
DRB1*0403 allele among DR4 subtypes. As in other populations, the
shared epitope in double dose is associated with RA development,
especially in its more severe forms. However, both development and
expression of severe forms of the disease were independent of the
shared epitope in a high proportion of patients, thus emphasising the
genetic heterogeneity of the disease and the possible involvement of
other genetic elements.
© 1997 by Annals of the Rheumatic Diseases
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