Non-inherited maternal HLA alleles are associated with rheumatoid arthritis.
BACKGROUND: Rheumatoid arthritis (RA) is strongly associated with a series of HLA-DRB1 alleles that encode a conserved sequence of amino acids ((70)Q/R K/R R A A(74)) in the DRbeta1 chain, known as the shared epitope (SE). However 30% of patients are negative for DRB1*04 and 15% are SE-negative. Exp...
| المؤلفون الرئيسيون: | , , , , |
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| التنسيق: | Journal article |
| اللغة: | English |
| منشور في: |
2003
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| _version_ | 1826281678939619328 |
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| author | Harney, S Newton, J Milicic, A Brown, M Wordsworth, B |
| author_facet | Harney, S Newton, J Milicic, A Brown, M Wordsworth, B |
| author_sort | Harney, S |
| collection | OXFORD |
| description | BACKGROUND: Rheumatoid arthritis (RA) is strongly associated with a series of HLA-DRB1 alleles that encode a conserved sequence of amino acids ((70)Q/R K/R R A A(74)) in the DRbeta1 chain, known as the shared epitope (SE). However 30% of patients are negative for DRB1*04 and 15% are SE-negative. Exposure to these alleles as non-inherited maternal antigens (NIMA) might explain this discrepancy. We undertook a family study to investigate the role of NIMA in RA. METHODS: One hundred families, including the RA proband and both parents, were recruited. HLA-DRB1 genotyping was performed using an allele-specific polymerase chain reaction by standard methods. The frequencies of NIMA and non-inherited paternal antigens (NIPA) were compared using contingency tables and a two-tailed P test. We then reviewed four previously published studies of NIMA in RA and conducted an analysis of the combined data RESULTS: We identified 36 families in which the proband was DRB1*04-negative and 13 in which the proband lacked the SE. There was an excess of DRB1*04 and SE NIMA (P=0.05) compared with NIPA. Combined analysis with previous studies showed that 53/231 mothers (23%) versus 25/205 fathers (12%) had a non-inherited DRB1*04 (P=0.003) and 30/99 mothers versus 18/101 fathers had a non-inherited SE allele (P=0.03). CONCLUSION: A role for HLA NIMA in RA is suggested by these results. |
| first_indexed | 2024-03-07T00:32:25Z |
| format | Journal article |
| id | oxford-uuid:804834db-a815-4131-84af-a44aa6a5feef |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T00:32:25Z |
| publishDate | 2003 |
| record_format | dspace |
| spelling | oxford-uuid:804834db-a815-4131-84af-a44aa6a5feef2022-03-26T21:22:07ZNon-inherited maternal HLA alleles are associated with rheumatoid arthritis.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:804834db-a815-4131-84af-a44aa6a5feefEnglishSymplectic Elements at Oxford2003Harney, SNewton, JMilicic, ABrown, MWordsworth, BBACKGROUND: Rheumatoid arthritis (RA) is strongly associated with a series of HLA-DRB1 alleles that encode a conserved sequence of amino acids ((70)Q/R K/R R A A(74)) in the DRbeta1 chain, known as the shared epitope (SE). However 30% of patients are negative for DRB1*04 and 15% are SE-negative. Exposure to these alleles as non-inherited maternal antigens (NIMA) might explain this discrepancy. We undertook a family study to investigate the role of NIMA in RA. METHODS: One hundred families, including the RA proband and both parents, were recruited. HLA-DRB1 genotyping was performed using an allele-specific polymerase chain reaction by standard methods. The frequencies of NIMA and non-inherited paternal antigens (NIPA) were compared using contingency tables and a two-tailed P test. We then reviewed four previously published studies of NIMA in RA and conducted an analysis of the combined data RESULTS: We identified 36 families in which the proband was DRB1*04-negative and 13 in which the proband lacked the SE. There was an excess of DRB1*04 and SE NIMA (P=0.05) compared with NIPA. Combined analysis with previous studies showed that 53/231 mothers (23%) versus 25/205 fathers (12%) had a non-inherited DRB1*04 (P=0.003) and 30/99 mothers versus 18/101 fathers had a non-inherited SE allele (P=0.03). CONCLUSION: A role for HLA NIMA in RA is suggested by these results. |
| spellingShingle | Harney, S Newton, J Milicic, A Brown, M Wordsworth, B Non-inherited maternal HLA alleles are associated with rheumatoid arthritis. |
| title | Non-inherited maternal HLA alleles are associated with rheumatoid arthritis. |
| title_full | Non-inherited maternal HLA alleles are associated with rheumatoid arthritis. |
| title_fullStr | Non-inherited maternal HLA alleles are associated with rheumatoid arthritis. |
| title_full_unstemmed | Non-inherited maternal HLA alleles are associated with rheumatoid arthritis. |
| title_short | Non-inherited maternal HLA alleles are associated with rheumatoid arthritis. |
| title_sort | non inherited maternal hla alleles are associated with rheumatoid arthritis |
| work_keys_str_mv | AT harneys noninheritedmaternalhlaallelesareassociatedwithrheumatoidarthritis AT newtonj noninheritedmaternalhlaallelesareassociatedwithrheumatoidarthritis AT milicica noninheritedmaternalhlaallelesareassociatedwithrheumatoidarthritis AT brownm noninheritedmaternalhlaallelesareassociatedwithrheumatoidarthritis AT wordsworthb noninheritedmaternalhlaallelesareassociatedwithrheumatoidarthritis |