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

L R Ryder; A Woetmann; H O Madsen; N Ødum; L P Ryder; H Bliddal; B Danneskiold-Samsøe; S. Ribel-Madsen; E M Bartels; Lisa Rebekka Ryder; Alex Le Woetmann Danielsen; H O Madsen; Niels Ødum; Lars P. Ryder; H Bliddal; B Danneskiold-Samsøe; S Ribel-Madsen; E M Bartels

doi:10.3109/03009740903555374

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

L R Ryder, A Woetmann, H O Madsen, N Ødum, L P Ryder, H Bliddal, B Danneskiold-Samsøe, S. Ribel-Madsen, E M Bartels, Lisa Rebekka Ryder, Alex Le Woetmann Danielsen, H O Madsen, Niels Ødum, Lars P. Ryder, H Bliddal, B Danneskiold-Samsøe, S Ribel-Madsen, E M Bartels

16 Citations (Scopus)

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.

Original language	English
Journal	Scandinavian Journal of Rheumatology
Volume	39
Issue number	4
Pages (from-to)	279-86
Number of pages	8
ISSN	0300-9742
DOIs	https://doi.org/10.3109/03009740903555374
Publication status	Published - 1 Aug 2010

Access to Document

10.3109/03009740903555374

Cite this

Ryder, L. R., Woetmann, A., Madsen, H. O., Ødum, N., Ryder, L. P., Bliddal, H., Danneskiold-Samsøe, B., Ribel-Madsen, S., Bartels, E. M., Ryder, L. R., Danielsen, A. L. W., Madsen, H. O., Ødum, N., Ryder, L. P., Bliddal, H., Danneskiold-Samsøe, B., Ribel-Madsen, S., & Bartels, E. M. (2010). Expression of full-length and splice forms of FoxP3 in rheumatoid arthritis. Scandinavian Journal of Rheumatology, 39(4), 279-86. https://doi.org/10.3109/03009740903555374

Ryder, LR, Woetmann, A, Madsen, HO, Ødum, N, Ryder, LP, Bliddal, H, Danneskiold-Samsøe, B, Ribel-Madsen, S, Bartels, EM, Ryder, LR, Danielsen, ALW, Madsen, HO, Ødum, N, Ryder, LP, Bliddal, H, Danneskiold-Samsøe, B, Ribel-Madsen, S & Bartels, EM 2010, 'Expression of full-length and splice forms of FoxP3 in rheumatoid arthritis', Scandinavian Journal of Rheumatology, vol. 39, no. 4, pp. 279-86. https://doi.org/10.3109/03009740903555374

@article{a3397160c55f11df825b000ea68e967b,

title = "Expression of full-length and splice forms of FoxP3 in rheumatoid arthritis",

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.",

author = "Ryder, {L R} and A Woetmann and Madsen, {H O} and N {\O}dum and Ryder, {L P} and H Bliddal and B Danneskiold-Sams{\o}e and S. Ribel-Madsen and Bartels, {E M} and Ryder, {Lisa Rebekka} and Danielsen, {Alex Le Woetmann} and Madsen, {H O} and Niels {\O}dum and Ryder, {Lars P.} and H Bliddal and B Danneskiold-Sams{\o}e and S Ribel-Madsen and Bartels, {E M}",

note = "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",

year = "2010",

month = aug,

day = "1",

doi = "10.3109/03009740903555374",

language = "English",

volume = "39",

pages = "279--86",

journal = "Scandinavian Journal of Rheumatology",

issn = "0300-9742",

publisher = "Taylor & Francis",

number = "4",

}

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 -

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

Abstract

Access to Document

Fingerprint

Cite this