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Weak association between HLAb27 and the spondylarthropathies in lebanon.

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388
ARTHRITIS & RHEUMATISM
Val. 40, No. 2, February 1997, pp 388-390
0 1997, American College of Rheumatology
CONCISE COMMUNICATIONS
Weak association between HLA-B27 and the
spondylarthropathies in Lebanon
The spondylarthropathies (SpA) include ankylosing
spondylitis (AS), psoriatic arthritis (PsA), Reiter’s syndrome
and reactive arthritis (ReA), rheumatic manifestations of
enterocolopathies (Ecp), some juvenile arthritides, and unclassified spondylarthropathies (uSpA) (1). The association with
HLA-B27 is one of the characteristics of SPA. In Western
populations, the frequency of HLA-B27 in AS patients and in
SpA patients in general is -90% and -60%, respectively (1,2).
The prevalence and diagnostic value of B27 in SpA have not
previously been studied in Lebanon or in any other Arabic
country in the Middle East. We report herein the results of
such a study in a Lebanese population.
Six rheumatologists prospectively recorded data on all
patients seen in their daily practices between January 6, 1995
and February 6, 1995. Two of them were in hospital practice;
the other 4 were in private practice in different areas of the
country. They completed a data sheet for all patients classified
as having SPA, according to medical history, clinical examination, and radiographs obtained before the day of consultation.
These patients were then screened for SPA using the preliminary European Spondylarthropathy Study Group (ESSG)
criteria (l),for AS using the 1984 New York modified criteria
(3), and for ReA (4). Patients who had a past or present
inflammatory bowel disease were included in the Ecp subgroup. Patients with past or present psoriatic lesions were
included in the PsA subgroup if they could not be classified in
any other SpA subgroup. For each SpA patient selected, the
next 2 patients having any rheumatic disease other than SpA
were included as controls.
All of the SpA and control patients had blood sampling, lymphocyte separation, and HLA-B27 typing performed
in the blood bank at HBtel Dieu de France in Beirut, Lebanon.
Frozen lymphocytes were then transferred to the Laboratoire
d’lmmunologie et d’HistocompatibilitC, Hapita1 Saint Louis,
Paris, France, for complete HLA class I determination. Both
determinations, i.e., those made in Beirut and those made in
France, were performed serologically, by microlymphocytotoxicity in Terasaki plates.
Eight hundred forty-one patients were seen during the
1-month-period of the study. They came mainly from the areas
of Beirut, Mount Lebanon, and the Bekaa. These regions
represent more than 75% of the Lebanese population. One
hundred five patients were classified as having SpA by rheumatologists. Seventy-two of them met the ESSG criteria, and
24 the modified criteria for AS, yielding prevalence rates of
8.56% for SPA (95% confidence interval [95% CI] 6.6-10.5%)
and 2.85% for AS (95% CI 1.44-3.91%). Two patients classified as having AS did not fulfill the ESSG criteria. The SpA
group included 22 patients with AS, 10 with PsA, 2 with ReA,
2 with Ecp, and 36 with uSpA. Thirteen patients had cutaneous
psoriasis; this was associated with AS in 2 of them and with an
Ecp in 1.
HLA class I typing was performed in 65 SpA patients
(19 with AS, 10 with PsA, 1 with ReA, 2 with Ecp, and 33 with
uSpA) and in 139 controls (11 with rheumatoid arthritis, 21
with osteoarthritis, 13 with other arthritides, 38 with degenerative disease of the spine, 33 with noninflammatory tendinitis,
8 with fibromyalgia, and 15 with miscellaneous disorders).
HLA-B27 was found in 9 SpA patients (5 with AS, 1 with PsA,
1 with ReA, and 2 with uSpA) and in 2 controls, yielding a
sensitivity of 13.8% in SpA and 26.3% in AS and a specificity
of 98.5% in both; odds ratios were 11 and 24.5, respectively.
There was no significant difference in the distribution of HLA
class I phenotypes between the SpA patients and the controls.
Table 1 shows the distribution of HLA serotyping in
SpA patients and controls in the present study compared with
3 different studies of HLA typing in the general population in
Lebanon; except for HLA-B5, which was not found in our
control group although it is usually frequent, our results were
comparable with previously published data on the Lebanese
population. HLA-B27 appears to be poorly linked to SpA in
the Lebanese population as compared with other Caucasian
populations. The observed odds ratio of 24.5 for the presence
of B27 in AS is much lower than the reported values, which
usually vary between 40 and 200 (2). The 1.4% prevalence of
B27 in our controls is comparable with the 1-2% previously
reported in the general Lebanese population (5,6).
Although the prevalence of SpA in this study was low,
similar frequencies of SpA and its subgroups are seen by
rheumatologists in Lebanon and in Europe (1,7). In a group of
2,228 patients seen in rheumatology clinics in France, the
authors observed a prevalence of SpA of 7.29%, which is
comparable with the value of 8.56% found in the present study.
However, our study was not population based, so definitive
prevalence rates of SpA in Lebanon are still unknown. HLAB27 was most strongly associated with AS and ReA. The
number of AS patients in our study was rather small, but AS
was probably underrepresented because we did not perform
radiography for the diagnosis of sacroiliitis in all patients; we
simply examined previously diagnosed patients on the day of
study consultation. Thus, some patients classified as having
uSpA could have had AS. The frequency of both cutaneous
psoriasis and inflammatory bowel disease was as expected and
thus could not explain the low frequency of B27. The patients
included in our study are representative of the general Lebanese population, as shown by the HLA distribution presented
in Table 1. Moreover, the majority of the people living in the
greater area of Beirut originate from different areas of
Lebanon.
In other populations in which the prevalence of B27 is
low, such as Japan (1%) and other countries of the Middle
East (3% in Israel and Iraq), the B27 prevalence remains
rather high among AS patients (80% in Japan and 60% in
Israel) (2). A 1-2% prevalence of B27 in the general population has also been observed in the Persian Gulf and in Ethiopia
(2), but no data are available on the association of B27 with AS
and SPA in these populations. A low association between
HLA-B27 and AS has been reported in the black population in
the US and is also suspected in the native Indonesian population (2). HLA-B40, and its splits HLA-B60 and HLA-B61,
reported in association with an increased susceptibility to AS
in HLA-B27 positive individuals (8), were also rare in our
patients. In addition, HLA-B39 was not increased in the B27
CONCISE COMMUNICATIONS
389
Table 1. Comparison of HLA class I phenotypes in spondylarthropathy (SpA) patients, control patients, and the general Lebanese
population *
Lebanese population
SPA
patients
Locus (n = 65)
A1
A2
A3
A1 1
A19
A23
A24
A26
A28
A29
A30
A3 1
A32
A33
BS
B7
B8
B13
B14
B18
B27
B35
B37
B38
B4 1
B44
B45
B49
B50
B5 1
853
B55
BS8
861
B62
B70
21.5
41.5
18.5
7.7
3.1
9.2
21.5
4.6
15.4
7.7
12.3
6.1
7.7
6.1
1.5
7.7
3.1
9.2
7.7
13.8
13.8
32.3
3.1
13.8
7.7
12.3
1.5
6.1
3.1
18.5
10.8
1.5
1.5
1.5
1.5
1.5
Controls
(n = 139)
16.4
40
12.9
13.6
0
8.5
18.6
12.1
13.6
4.3
9.3
1.4
9.3
10
0
5
5.7
1.4
13.6
17.9
1.4
29.3
2.1
6.4
13.6
10.7
2.9
4.3
7.4
14.3
0.7
3.6
0.7
1.4
1.4
2.9
Serre et a1 Abdelnoor
(ref. 5 )
(ref. 6)
(n = 315) (n = 416)
15.1
21.2
11.9
4.2
NA
NA
NA
NA
7.6
2.8
NA
NA
NA
NA
9.8
3.5
1.8
6.1
2.7
8.1
1.7
26.4
NA
2.9
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
27
40
21
5
NA
NA
NA
NA
10
10
11
5
5
8
23
7
6
9
5
9
2
32
1.5
NA
1.5
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
Mansour
(n = 130)t
19.2
40
16.1
6.9
27.7
5.3
39.2
8.4
7.6
6.9
10
0
13
6.1
26.9
10.7
0.8
4.6
10
14.6
0.8
34.6
3
6.9
14
11.5
2.3
9.2
5.3
14.6
1.s
3
2.3
1.5
2.3
1.7
* Values are the percentages of subjects with the different phenotypes
identified. Some rare phenotypes found in the general population but
not in our patients are not shown. NA = data not available.
i Unpublished recent data from our blood bank, showing serotypes
absent from previous studies.
negative patients, in contrast to what has recently been described (9). No other class I allele was significantly associated
with SpA in our study, but HLA class I1 typing is in progress to
better characterize our population. Our results indicate that
non-B27 disease-predisposing factors play a much stronger
role in the disease in this particular population than in others.
This could be related to the peculiar history and population
mixing in our country. Further studies are needed to confirm
the weak link between HLA-B27 and SpA in other populations of the Middle East, and to observe if B27-negative
patients have milder clinical disease than those who are
B27-positive. Family studies are also needed to identify the
gene(s) associated with SpA in Lebanon.
Supported by grants ji-om the National Scientific Research
Council, Beirut, Lebanon, and from pfizer Lebanon. Drs. Awada and
Tamouza contributed equally to this work.
H. Awada, MD
R. Baddoura, MD
R. Naman, MD, FRCP
S. Klayme, PhD
I. Mansour, PhD
H6tel Dieu de France
Beirut, Lebanon
R. Tamouza, MD
F. Marzais
C. Raffoux, MD
A. Toubert, MD
D. Charron, MD
H6pital Saint Louis
Paris, France
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in Japanese patients with systemic lupus
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Recently, associations of interleukin-1 receptor antagonist (IL-1Ra) gene polymorphism with several inflammatory
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