Non-inherited maternal HLA alleles are associated with rheumatoid arthritis

Harney, S., Newton, J., Milicic, A., Brown, M. A., & Wordsworth, B. P. (2003) Non-inherited maternal HLA alleles are associated with rheumatoid arthritis. Rheumatology, 42(1), pp. 171-174.

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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 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.


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


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 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.

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ID Code: 89546
Item Type: Journal Article
Refereed: Yes
Additional Information: Cited By :31
Export Date: 21 September 2015
Correspondence Address: Harney, S.; Nuffield Orthopaedic Centre, Windmill Road, Headington, Oxford OX3 7LD, United Kingdom; email:
Keywords: HLA, Non-inherited maternal alleles, Rheumatoid arthritis, Shared epitope, epitope, HLA DR antigen, allele, article, contingency table, controlled study, family study, female, gene frequency, genetic association, genotype, human, male, pathogenesis, polymerase chain reaction, priority journal, statistical analysis, Alleles, Arthritis, Rheumatoid, Cohort Studies, Epitope Mapping, Fathers, Genes, MHC Class II, Genetic Markers, HLA-DR Antigens, Humans, Mothers, Odds Ratio
DOI: 10.1093/rheumatology/keg059
ISSN: 1462-0324
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2003 Oxford Journals
Deposited On: 27 Oct 2015 01:00
Last Modified: 27 Oct 2015 01:00

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