非遗传的母体HLA等位基因与类风湿性关节炎相关。

Non-inherited maternal HLA alleles are associated with rheumatoid arthritis.

作者信息

Harney S, Newton J, Milicic A, Brown M A, Wordsworth B P

机构信息

Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.

出版信息

Rheumatology (Oxford). 2003 Jan;42(1):171-4. doi: 10.1093/rheumatology/keg059.

DOI:10.1093/rheumatology/keg059

PMID:12509632

Abstract

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 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.

摘要

背景

类风湿关节炎（RA）与一系列HLA - DRB1等位基因密切相关，这些等位基因在DRβ1链中编码一段保守的氨基酸序列（(70)Q/R K/R R A A(74)），即共享表位（SE）。然而，30%的患者DRB1*04呈阴性，15%的患者SE呈阴性。作为非遗传母体抗原（NIMA）接触这些等位基因可能解释了这种差异。我们进行了一项家族研究以调查NIMA在RA中的作用。

方法

招募了包括RA先证者及其父母在内的100个家庭。采用标准方法通过等位基因特异性聚合酶链反应进行HLA - DRB1基因分型。使用列联表和双尾P检验比较NIMA和非遗传父体抗原（NIPA）的频率。然后我们回顾了之前发表的四项关于RA中NIMA的研究，并对合并数据进行了分析。

结果

我们确定了36个先证者DRB104呈阴性的家庭和13个先证者缺乏SE的家庭。与NIPA相比，DRB104和SE NIMA过量（P = 0.05）。与之前研究的合并分析表明，53/231名母亲（23%）与25/205名父亲（12%）有非遗传的DRB1*04（P = 0.003），30/99名母亲与18/101名父亲有非遗传的SE等位基因（P = 0.03）。