HLA heterozygosity contributes to susceptibility to rheumatoid arthritis.
We have investigated the role of HLA-DR genotypes in 184 patients with severe rheumatoid arthritis (RA) and in 46 patients with Felty syndrome, to establish the relative contribution of the RA-associated subtypes of DR4 (Dw4, Dw14, and Dw15). There was an excess of DR4 homozygotes, particularly Dw4/...
| Main Authors: | , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
1992
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| _version_ | 1826270683572731904 |
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| author | Wordsworth, B Pile, K Buckely, J Lanchbury, J Ollier, B Lathrop, M Bell, J |
| author_facet | Wordsworth, B Pile, K Buckely, J Lanchbury, J Ollier, B Lathrop, M Bell, J |
| author_sort | Wordsworth, B |
| collection | OXFORD |
| description | We have investigated the role of HLA-DR genotypes in 184 patients with severe rheumatoid arthritis (RA) and in 46 patients with Felty syndrome, to establish the relative contribution of the RA-associated subtypes of DR4 (Dw4, Dw14, and Dw15). There was an excess of DR4 homozygotes, particularly Dw4/Dw14 compound heterozygotes (relative risk [RR] 49). The risk associated with Dw4 depended on the other allele present--Dw4/DR1 (RR 21), Dw4/Dw4 (RR 15), and Dw4/DRX (RR 6). There was a significant risk from Dw4/Dw14 compared with Dw4/Dw4, both in those with severe RA (RR 2.9; P less than .02) and in those with Felty syndrome (RR 4.2; P less than .02). In contrast, in a further 63 known DR4 homozygotes with RA, not selected for severe disease, the excess of Dw4/Dw14 was much less striking (RR 1.4; not significant), suggesting that this genotype may be particularly associated with more severe disease. We also found four cases with the rare Dw4/Dw15 genotype (expected less than or equal to 0.5; P less than or equal to .02). Since the Dw4, Dw14, Dw15, and DR1 molecules have similar antigen-binding sites and since combinations of these alleles particularly predispose to severe RA, we suggest that synergistic mechanisms are involved. These could include an effect on T-cell repertoire selection. |
| first_indexed | 2024-03-06T21:44:40Z |
| format | Journal article |
| id | oxford-uuid:4925ce72-a3ad-4d00-9984-80a64f960a2c |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T21:44:40Z |
| publishDate | 1992 |
| record_format | dspace |
| spelling | oxford-uuid:4925ce72-a3ad-4d00-9984-80a64f960a2c2022-03-26T15:29:54ZHLA heterozygosity contributes to susceptibility to rheumatoid arthritis.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:4925ce72-a3ad-4d00-9984-80a64f960a2cEnglishSymplectic Elements at Oxford1992Wordsworth, BPile, KBuckely, JLanchbury, JOllier, BLathrop, MBell, JWe have investigated the role of HLA-DR genotypes in 184 patients with severe rheumatoid arthritis (RA) and in 46 patients with Felty syndrome, to establish the relative contribution of the RA-associated subtypes of DR4 (Dw4, Dw14, and Dw15). There was an excess of DR4 homozygotes, particularly Dw4/Dw14 compound heterozygotes (relative risk [RR] 49). The risk associated with Dw4 depended on the other allele present--Dw4/DR1 (RR 21), Dw4/Dw4 (RR 15), and Dw4/DRX (RR 6). There was a significant risk from Dw4/Dw14 compared with Dw4/Dw4, both in those with severe RA (RR 2.9; P less than .02) and in those with Felty syndrome (RR 4.2; P less than .02). In contrast, in a further 63 known DR4 homozygotes with RA, not selected for severe disease, the excess of Dw4/Dw14 was much less striking (RR 1.4; not significant), suggesting that this genotype may be particularly associated with more severe disease. We also found four cases with the rare Dw4/Dw15 genotype (expected less than or equal to 0.5; P less than or equal to .02). Since the Dw4, Dw14, Dw15, and DR1 molecules have similar antigen-binding sites and since combinations of these alleles particularly predispose to severe RA, we suggest that synergistic mechanisms are involved. These could include an effect on T-cell repertoire selection. |
| spellingShingle | Wordsworth, B Pile, K Buckely, J Lanchbury, J Ollier, B Lathrop, M Bell, J HLA heterozygosity contributes to susceptibility to rheumatoid arthritis. |
| title | HLA heterozygosity contributes to susceptibility to rheumatoid arthritis. |
| title_full | HLA heterozygosity contributes to susceptibility to rheumatoid arthritis. |
| title_fullStr | HLA heterozygosity contributes to susceptibility to rheumatoid arthritis. |
| title_full_unstemmed | HLA heterozygosity contributes to susceptibility to rheumatoid arthritis. |
| title_short | HLA heterozygosity contributes to susceptibility to rheumatoid arthritis. |
| title_sort | hla heterozygosity contributes to susceptibility to rheumatoid arthritis |
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