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Rheumatology 2003; 42: 171-174
© 2003 British Society for Rheumatology

Non-inherited maternal HLA alleles are associated with rheumatoid arthritis

S. Harney1,2,, J. Newton1,2, A. Milicic1, M. A. Brown1,2 and B. P. Wordsworth1,2

1 Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN and
2 Nuffield Orthopaedic Centre, Oxford OX3 7LD, UK

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 DRß1 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.

KEY WORDS: Rheumatoid arthritis, Shared epitope, Non-inherited maternal alleles, HLA.

Correspondence to: S. Harney, c/o Seddon Ward, Nuffield Orthopaedic Centre, Windmill Road, Headington, Oxford OX3 7LD, UK. E-mail: sineadharney{at}hotmail.com


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Home page
 Ann Rheum DisHome page
K A Guthrie, N R Tishkevich, and J L Nelson
Non-inherited maternal human leukocyte antigen alleles in susceptibility to familial rheumatoid arthritis
Ann Rheum Dis, January 1, 2009; 68(1): 107 - 109.
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