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...

Ful tanımlama

Detaylı Bibliyografya
Asıl Yazarlar: Harney, S, Newton, J, Milicic, A, Brown, M, Wordsworth, B
Materyal Türü: Journal article
Dil:English
Baskı/Yayın Bilgisi: 2003
_version_ 1826281678939619328
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