HLA-DRB, HLA-DQA, AND HLA-DQB POLYMORPHISM IN CELIAC-DISEASE AND ENTEROPATHY-ASSOCIATED T-CELL LYMPHOMA - COMMON FEATURES AND ADDITIONAL RISK-FACTORS FOR MALIGNANCY

被引:71
作者
HOWELL, WM
LEUNG, ST
JONES, DB
NAKSHABENDI, I
HALL, MA
LANCHBURY, JS
CICLITIRA, PJ
WRIGHT, DH
机构
[1] UNIV PATHOL SOUTHAMPTON,SOUTHAMPTON GEN HOSP,SOUTHAMPTON,HANTS,ENGLAND
[2] GLASGOW ROYAL INFIRM,GASTROENTEROL UNIT,GLASGOW G4 0SF,LANARK,SCOTLAND
[3] UNIV LONDON,UNITED MED & DENT SCH GUYS & ST THOMAS,DIV MED,IMMUNOGENET MOLEC LAB,LONDON,ENGLAND
[4] UNIV LONDON,UNITED MED & DENT SCH,RAYNE INST,LONDON,ENGLAND
关键词
D O I
10.1016/0198-8859(94)00130-I
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
CD is a gluten-sensitive enteropathy, strongly associated with expression of the DQA1(*)0501, DQB1(*)0201 genotype. CD patients have an increased risk of malignancy, particularly EATCL. However, it is controversial as to whether adults with EATCL represent a subgroup of patients with CD or should be regarded as a distinct entity. To investigate the genetic relationship between CD and EATCL, HLA class II DRB1, DQA1, and DQB1 typing of peripheral blood, frozen or paraffin-embedded biopsy tissue obtained from Caucasian patients with CD (n = 91) or EATCL (n = 47) was performed by PCR-SSOP typing. Genotype frequencies were compared with those observed in 151 unrelated control individuals. A total of 83 (91%) of 91 CD patients were of DQA1(*)0501, DQB1(*)0201 genotype (p(c) < 10(-6), RR = 522.2), compared with 40 (93%) of 43 EATCL patients (p(c) < 10(-6) RR = 44.2) with amplifiable DNA versus 35 (23%) of 151 controls. DRB1(*)03 frequencies were also elevated in both patient groups (79 of 91 in CD [87%; p(c) < 10(-6), RR = 24.5] and 38 of 40 in EATCL [95%; p(c) < 10(-6), RR = 70.7]) compared with controls (32 of 151, 21%). These results confirm previous studies of HLA associations in CD and also suggest that EATCL arises in individuals with the DQA1(*)0501, DQB1(*)0201 CD-predisposing genotype. However, the frequency of DRB1(*)03,04 heterozygotes was significantly increased in the EATCL group (16 of 40, 40%) compared with both control individuals (3 of 151, 2%; p(c) < 10(-6), RR = 32.9) and uncomplicated CD patients (6 of 91, 7%; p(c) = 0.04, RR = 9.4). Conversely, DRB1(*)03,03 homotozygotes and DRB1(*)03,07 heterozygotes were significantly increased in frequency in the CD but not the EATCL series, compared with controls (for DRB1(*)03,03, p(c) = 0.006, RR = 8.5; for DRB1(*)03,07, p(c) = 0.06, RR = 7.9), reflecting a significant decrease in DRB1(*)07 frequency in the EATCL patient group (8%) as compared with the CD series (39%; p(c) = 0.017, RR = 0.13). In addition, none of the 38 DQA1(*)0501, DQB1(*)0201 EATCL patients were homozygous for DQB1(*)0201, compared with 44 of 83 (53%) DQA1(*)0501, DQB1(*)0201 CD patients (p(c) < 10, RR < 0.02) and 12 of 32 (38%) DQA1(*)0501, DQB1(*)0201 controls (p(c) < 0.02, RR < 0.05). These results suggest that while EATCL arises in individuals with the DQA1(*)0501, DQB1(*)0201 CD-predisposing genotype, additional HLA-DR/DQ-associated alleles acting independently or in association with known CD-associated genotypes may represent a risk factor for EATCL.
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页码:29 / 37
页数:9
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