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Scand J Rheumatol. 2010 Aug;39(4):279-86. doi: 10.3109/03009740903555374.

Expression of full-length and splice forms of FoxP3 in rheumatoid arthritis.

Author information

  • 1Department of Immunology, University of Copenhagen, The Parker Institute, Frederiksberg Hospital, Rigshospitalet, Denmark. parker@frh.regionh.dk

Abstract

OBJECTIVE:

The aim of our study was to compare the presence of full-length and alternative splice forms of FoxP3 mRNA in CD4 cells from rheumatoid arthritis (RA) patients and healthy controls.

METHODS:

A quantitative real-time polymerase chain reaction (QRT-PCR) method was used to measure the amount of FoxP3 mRNA full-length and splice forms. CD4-positive T cells were isolated from peripheral blood from 50 RA patients by immunomagnetic separation, and the FoxP3 mRNA expression was compared with the results from 10 healthy controls.

RESULTS:

We observed an increased expression of full-length FoxP3 mRNA in RA patients when compared to healthy controls, as well as an increase in CD25 mRNA expression, but no corresponding increase in CTLA-4 mRNA expression. The presence of an alternative splice form of FoxP3 lacking exon 2 was confirmed in both RA patients and healthy controls, but with no significant difference in expression between the two groups. There was a positive correlation between the amount of FoxP3 mRNA and the clinical inflammation parameters C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), and a negative correlation between FoxP3 mRNA and the dose of methotrexate (MTX) given to the patients.

CONCLUSION:

RA patients express more full-length FoxP3 than healthy controls in peripheral blood CD4-positive cells, suggesting an increased number of regulatory T cells (Tregs). However, no concomitant increase in CTLA-4 expression was seen. We therefore propose that the Tregs are left unable to suppress the ongoing inflammation due to a deficiency in CTLA-4 needed for cell contact-dependent suppression.

PMID:
20476861
DOI:
10.3109/03009740903555374
[PubMed - indexed for MEDLINE]
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