Annals ofthe Rheumatic Diseases 1990; 49: 318-319
HLA antigens in psoriatic arthritis subtypes of a
J C Torre Alonso, A Rodriguez Perez, Eliecer Coto
HLA-A, B, and C antigens were studied in 104
Spanish patients with psoriatic arthritis. Dif-
ferent clinical features were evaluated and the
patients divided into disease subsets. HLA-
B17, B27, B16, and Cw6 were the most
common haplotypes in the total group. The
HLA-B17/Cw6 haplotype was increased in
patients with oligoarthritis. The increase of
antigen B17 correlated with oligoarthritis and
spondarthritis, whereas Cw6 was more signi-
ficant in oligoarthritis. The prevalence of the
B27/Cwl haplotype was greater in association
with spondarthritis and was probably related
to the B27.5 subtype linked to Cwl. A signifi-
cantnegative association betweentheB44/Cw5
haplotype and psoriatic arthritis was found.
The existence of several haplotypic factors in
the different subsets is discussed. Lack of one
or more HLA factors is thought to be respon-
sible forthe different clinicalforms ofpsoriatic
between susceptibility of psoriatic arthritis and
HLA-B17, B13, B27, B37 antigens."'
antigen association seems to be secondary to the
stronger Cw6 association.5 Studies of different
families have shown that the HLA genetic
factor plays a major part in the development of
psoriatic arthritis,6 7 but its mode of inheritance
is at present unclear.8 Different HLA class I
antigens may be linked to psoriatic arthritis
susceptibility in different populations, but the
relation between HLA antigens and clinical
subsets of psoriatic
sufficiently investigated. The aim of this study
was to map susceptibility genes within the HLA
in a large sample of Spanish subjects with
psoriatic arthritis using available HLA markers,
and to correlate the prevalence of these markers
with subsets of different clinical features.
studies have found
HLA-A, B, and C typing was carried out by a
standard microlymphocytotoxicity technique on
peripheral lymphocytes.9 Local and 9th HLA
Workshop antisera were used.
Data were analysed by a computer program.
When the antigen prevalences deviated signifi-
cantly from those of normal subjects the corres-
ponding p values were multiplied by the number
of antigens, which were only considered when
there were more than 20. The x2 test was used to
compare the prevalences of HLA antigens, and
Yates's correction was applied. Relative risk
(RR) was also calculated according to Sveigaard
Table 1 lists the prevalences of HLA-A, B, and
C antigens in 104 patients with psoriatic arthritis
and in the controls. Significant association was
found between psoriatic arthritis and HLA-
B17, B27, B16 (table
results.2 3 HLA-B17, which
1), which confirmed
Table 1: Prevalence of relevant HLA antigens in 104
northern Spanish patients and in controls
NS Covadonga, Oviedo,
Reunato lgia, Hospital
NS Covadong, Oviedo,
J C Toffe Alonso
A Rodriguez Perez
Inmunologia, Hospital NS
Covadonga, cNVillamil s/n,
33006 Oviedo, Spain.
Accepted for publication
10 July 1989
Patients and methods
HLA-A, B, and C antigens were studied in 104
unrelated patients with psoriatic arthritis. The
diagnostic critena used were those established
by Moll and Wright.7 Healthy volunteers (109)
from a sample of the Spanish population served
as controls. Several clinical features were evalu-
ated and the patients divided into disease
subsets: 36 had oligoarthritis, 30 polyarthritis,
spondarthritis. Moreover, five had
arthritis mutilans and five the distal form with
involvement of the distal interphalangeal joint.
Table 2: HLA antigens in psoriatic arthritis subsets. Values
are shmon as the percentage ofpatients in each subset
possesstng a partiular antigen with relative nsk in
*p<0-05; **p<0-025; ***p<0-01; ****p<0-005.
HLA antigens inpsoriatic arthritis
linkage disequilibrium with Cw6,2A was signi-
Additionally, B44, Cw4, and CwS were de-
creased, though not significantly, in psoriatic
arthritis. When different groups were analysed
(table 2) the antigen B17 was relevant in both
oligoarthritis (RR=5-9; p<0 05) and spond-
arthritis (RR=6-6; p<0 05). The antigen Cw6
had an important relative risk only in oligo-
arthritis (RR= 10; p<0-01); it was absent in
spondarthritis. In contrast, B27 was more
prevalent in patients with spondarthritis (RR=
38-8; p<0005). The increase in the Cwl
antigen in spondarthritis wasprobablysecondary
to the noted B27 association (RR=5-4; p<0 05).
Correlation was found between B7, B37 and the
polyarticular form (table 2).
Several studies have sought an association
between susceptibility to psoriatic arthritis and
the HLA antigens. Psoriatic arthritis has been
reported to be associated with HLA-B17, B37,
B13, and Cw6.2A Our study was performed in
a large group of Spanish patients with psoriatic
arthritis. The results are in agreement with
those found byotherauthors in Caucasoids.
The B17 antigen is related to oligoarthritis and
spondarthritis subsets in the Spanish population.
Cw6 is more strongly associated with oligo-
arthritis than with polyarthritis. These findings
have not been described previously. It has been
noted, however, that the B17/Cw6 haplotype in
Caucasoids is weakly maintained in the Spanish
population.9 These facts support the idea that
B17 and Cw6 might act as independent genetic
factors of susceptibility, resulting in different
clinicalmanifestations. Nevertheless, therelative
risk in oligoarthritis is higher for patients with
B17/Cw6 than for those with B17 alone. Several
closely linked factors promoting susceptibility
to psoriatic arthritis may exist within an HLA
haplotype (B17/Cw6). All may be necessary for
the occurrence of oligoarthritis. Lack of one or
more factors (B17 in polyarthritis, Cw6 in
spondarthritis) might lead to the different clini-
cal forms. In patients tested B27 is increased
and correlates with a spondarthritis subset. The
Cwl association found with psoriatic arthritis is
secondary to B27. Several studies show the
existence ofat least seven B27 subtypes.12 13 An
interesting question is whether the association
of B27 with psoriatic arthritis involves just one
B27 subtype. HLA-B27
is in linkage dis-
equilibrium with Cwl and Cw2 in Caucasoids. 13
The HLA-B27.5 subtype is in linkage dis-
equilibrium with both Cwl and Cw2. On the
other hand, B27.2 is almost exclusively linked
to Cw2. The results (increase of B27/Cwl in
spondarthritis) suggest that B27.5 is probably
analysis by isoelectric focusing
needed for confirmation of this. This result
contrasts with the Cw2 increase described by
Gladman et al, which is probably secondarily
associated with both B27.2 and B27.5 subtypes
in American patients.3 The association of B37
and B13 with psoriatic arthritis seems to be
secondary to the stronger Cw6 association. The
negative association of the B44/Cw5 haplotype
has not been previously reported and may have
a protective role against the development of
These findings further support the hypothesis
that psoriatic arthritis is a heterogeneous dis-
order. Several closely linked psoriatic arthritis
susceptibility factors may exist within an HLA
haplotype. Their presence may be necessary for
the development of psoriatic arthritis. Absence
ofone or several HLA susceptibility factors may
lead to the development of different clinical
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