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

TY - JOUR

T1 - Expression of full-length and splice forms of FoxP3 in rheumatoid arthritis

AU - Ryder, L R

AU - Woetmann, A

AU - Madsen, H O

AU - Ødum, N

AU - Ryder, L P

AU - Bliddal, H

AU - Danneskiold-Samsøe, B

AU - Ribel-Madsen, S.

AU - Bartels, E M

AU - Ryder, Lisa Rebekka

AU - Danielsen, Alex Le Woetmann

AU - Madsen, H O

AU - Ødum, Niels

AU - Ryder, Lars P.

AU - Bliddal, H

AU - Danneskiold-Samsøe, B

AU - Ribel-Madsen, S

AU - Bartels, E M

N1 - Keywords: Adult; Aged; Aged, 80 and over; Arthritis, Rheumatoid; CD4-Positive T-Lymphocytes; Female; Flow Cytometry; Forkhead Transcription Factors; Humans; Male; Middle Aged; RNA, Messenger; Reverse Transcriptase Polymerase Chain Reaction

PY - 2010/8/1

Y1 - 2010/8/1

N2 - 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.

AB - 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.

U2 - 10.3109/03009740903555374

DO - 10.3109/03009740903555374

M3 - Journal article

C2 - 20476861

SN - 0300-9742

VL - 39

SP - 279

EP - 286

JO - Scandinavian Journal of Rheumatology

JF - Scandinavian Journal of Rheumatology

IS - 4

ER -