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HLA-DR specificities among Japanese with rheumatoid arthritis.

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HLA-DR specificities among Japanese with
rheumatoid arthritis
To the Editor:
The susceptibilityof whites to rheumatoid arthritis (RA) has been associated with HLA-DR4 in patients
with seropositive RA (1-5). Because of racial differences in the frequencies of HLA specificities, however,
typing results for whites have not been considered applicable to Japanese patients with RA. We therefore investigated the frequencies of HLA-A, B, C, and DR antigens in Japanese patients with seropositive RA.
HLA-A, B, C, and DR typing was performed on
peripheral blood lymphocytes from 50 Japanese patients (40 female, 10 male) with classic or definite RA
(6) and from 144 controls, using the standard microdroplet lymphocyte cytotoxicity test (7). Forty-four patients were seropositive, with titer ? 2 by Rose-Waller
reaction, a RAHA test (Fuji Zoki Co., Tokyo), and a
positive latex test for rheumatoid factor. Six were seronegative (negative in both the RAHA and latex tests).
The frequencies of the A, B, and C locus specificities did not differ substantially between the patients
and unaffected controls. The difference in the frequency
of HLA-DR4 (54% in patients and 33% in controls) was
not statistically significant.
In contrast, the frequency of DR4 was increased
significantly (2= 8.85; corrected P < 0.03; relative risk
[IT]= 2.98) in the seropositive group (59%) as compared
with the controls (33%) when the 2 groups were divided
into seropositive and seronegative groups. No association between the DR4 and the seronegative groups
(33%) was observed (2= 0.16; P > 0.689, rr = 1.03). In
addition, 9 of the 10 male patients had HLA-DR4.
In Japanese with RA, significant associations
with Bw54-DYT, DR4, and MT3 (2= 6.34; rr = 2.36
for DR 4) were observed by Sasazuki (8). We found no
significant associations with the B or C locus specificities; there was an increase in the DR4 ($ = 6.30, rr =
2.40) of the total patients, but the difference was not statistically significant. When the 2 groups were divided
Table 1. Frequency of HLA-DR4 in patients with RA
Age range (mean), years
DR4 positive (normal 33%)'
Corrected P
Relative risk
(n = 44)
(n = 6)
33-61 (45)
3 1-72 (49)
* Frequency in 144 healthy Japanese.
into seropositive and seronegative groups, the association with DR4 in the seropositive and the lack of association with DR4 in the seronegative group were observed, as in white patients.
Sasazuki stated that male patients had a stronger
association with HLA-MT3 than female patients. We
found that 9 of our 10 male patients had HLA-DR4.
Because the number of male patients was small, it is difficult to generalize; we believe more cases should be examined.
After considering our results and those of Sasazuki, we suggest that HLA-DR4 genes are those which
control susceptibility to RA among Japanese.
Second Division
Department of Internal Medicine
Kyoto University
53 Kawaracho, Shogoin, Sakyo-ku
Kyoto 606, Japan, and
Department of Surgery
University of California School of Medicine
Los Angeles, CA
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2. Dobloug JH, FBrre @, Thorsby E: HLA-DR4 and rheumatoid arthritis. Lancet k548-549, 1979
3. McMichael AJ, Sasazuki T, McDevitt HO, Payne RO: Increased frequency of HLA-CW3 and HLA-DW4 in rheumatoid arthritis. Arthritis Rheum 20: 1037-1042, 1977
4. Stastny P: Association of the B-cell alloantigen DRW4
with rheumatoid arthritis. N Engl J Med 298:869-871, 1978
5. Nakai Y, Wakisaka A, Aizawa M, Itakura K, Nakai H,
Ohashi A: HLA and rheumatoid arthritis in the Japanese.
Arthritis Rheum 24:722-725, 1981
6. Ropes MW, Bennet GA, Cobb S, Jacox R, Jessar RA: Revision of diagnostic criteria for rheumatoid arthritis. Bull
Rheum Dis 9:175-176, 1958
7. Terasaki PI, Bernoco D, Park MS,Ozturk G, Iwaki Y: Microdroplet testing for HLA-A, -B, -C and -D antigen. Am J
Clin Pathol69:103-120, 1978
8. Sasazuki T, Ohta N, Nishimura UK, Abe T, Abe C, Shiokawa Y: Japanese rheumatoid arthritis patients and HLA,
New Horizons on Rheumatoid Arthritis. Edited by Y
Shiokawa, Y Yamamouchi, T Abe. Amsterdam, Excerpta
Medica, 1981 (in press)
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japanese, hla, arthritis, among, specificities, rheumatoid
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