ABSTRACT: OBJECTIVE:: HLA-DRB1 alleles associated with risk of rheumatoid arthritis (RA) encode similar HLA-DRβ1 sequences referred to as the "shared epitope" (SE). The most common SE sequences are QKRAA and QRRAA. A substantial number of RA patients, nevertheless, lack the SE. Bi-directional fetal-maternal trafficking results in long-term persistence of fetal cells in the mother and maternal cells in her offspring, referred to as microchimerism (Mc). We asked whether RA patients who lack the SE can acquire the SE through Mc. METHODS:: We developed specific real-time quantitative PCR (qPCR) assays for the SE encoded sequences QKRAA and QRRAA. DNA extracted from peripheral blood mononuclear cells was tested with the SE-specific qPCR assays. A total of 86 subjects who were negative for the SE were studied, 52 women with RA and 34 healthy women. RESULTS:: Mc with the SE was found significantly more often in RA patients than controls, odds ratio 4.1, 95% CI 1.6-10.0, p=0.003. Concentrations of SE Mc were also significantly higher among RA patients than controls, p=0.002. When analyzed separately for SE type, the prevalence of QKRAA Mc in RA vs. healthy women respectively was 17% vs. 3% (9/52 vs. 1/34, p=0.03) and of QRRAA 40% vs. 18% (21/52 vs. 6/34, p=0.04). Mc concentrations were also higher in RA than healthy subjects for QKRAA (p=0.03) and QRRAA (p=0.03). CONCLUSION:: Results indicate RA patients who genotypically lack the SE can acquire the SE as persistent Mc from maternal-fetal cell exchange and suggest SE-encoding Mc could be a risk factor for RA.
Arthritis & Rheumatism 11/2010; · 7.87 Impact Factor