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 (70Q/R K/R R A A74) in the DRβ1 chain, known as the shared epitope (SE). However 30% of patients are negative for DRB1*04 and 15% are SE‐negative. Exposure t...

Full description

Saved in:

Bibliographic Details
Published in:	British journal of rheumatology 2003-01, Vol.42 (1), p.171-174
Main Authors:	Harney, S., Newton, J., Milicic, A., Brown, M. A., Wordsworth, B. P.
Format:	Article
Language:	eng
Subjects:	Alleles Arthritis, Rheumatoid - immunology Biological and medical sciences Cohort Studies Diseases of the osteoarticular system Epitope Mapping Fathers Female Gene Frequency Genes, MHC Class II Genetic Markers HLA HLA-DR Antigens - genetics HLA-DRB1 Chains Humans Inflammatory joint diseases Male Medical sciences Mothers Non‐inherited maternal alleles Odds Ratio Rheumatoid arthritis Shared epitope
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Background. Rheumatoid arthritis (RA) is strongly associated with a series of HLA‐DRB1 alleles that encode a conserved sequence of amino acids (70Q/R K/R R A A74) in the DRβ1 chain, known as the shared epitope (SE). However 30% of patients are negative for DRB104 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 DRB104‐negative and 13 in which the proband lacked the SE. There was an excess of DRB104 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 DRB104 (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.
ISSN:	1462-0324 1460-2172 1462-0332 1460-2172