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Rheumatoid arthritis synovial fibroblasts produce a soluble form of the interleukin-7 receptor in response to pro-inflammatory cytokines.

Badot V, Durez P, Van den Eynde BJ, Nzeusseu-Toukap A, Houssiau FA, Lauwerys BR - J. Cell. Mol. Med. (2011)

Bottom Line: We found that exposure of RA FLS to pro-inflammatory cytokines (TNF-α, IL-1β and combinations of TNF-α and IL-1β or TNF-α and IL-17) induces sIL-7R secretion.In DMARD-resistant patients, high sIL-7R serum concentrations are strongly associated with poor response to TNF-blockade.In conclusion, sIL-7R is induced by pro-inflammatory cytokines in RA FLS. sIL-7R could qualify as a new biomarker of response to therapy in RA.

View Article: PubMed Central - PubMed

Affiliation: Rheumatology Department, Cliniques Universitaires Saint-Luc, Université catholique de Louvain, Brussels, Belgium.

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Related in: MedlinePlus

sIL-7R serum concentrations predict response to TNF blockade in RA. (A) sIL-7R titres measured by sandwich ELISA in duplicate baseline serum samples obtained in DMARD-resistant RA patients treated with 3 mg/kg infliximab. Patients were categorized in good-responders (circles), moderate- (triangles) and non-responders (squares) according to EULAR response criteria. The horizontal bar depicts the median value in each group. (B) Linear correlation between baseline sIL-7R serum levels and DAS-Score differences (follow-up minus baseline DAS28-CRP). (C) Receiving operating characteristic curve evaluating the value of baseline sIL-7R in predicting response to therapy. The curve was plotted by calculating sensitivity and specificity of the test at several cut-off values.
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fig04: sIL-7R serum concentrations predict response to TNF blockade in RA. (A) sIL-7R titres measured by sandwich ELISA in duplicate baseline serum samples obtained in DMARD-resistant RA patients treated with 3 mg/kg infliximab. Patients were categorized in good-responders (circles), moderate- (triangles) and non-responders (squares) according to EULAR response criteria. The horizontal bar depicts the median value in each group. (B) Linear correlation between baseline sIL-7R serum levels and DAS-Score differences (follow-up minus baseline DAS28-CRP). (C) Receiving operating characteristic curve evaluating the value of baseline sIL-7R in predicting response to therapy. The curve was plotted by calculating sensitivity and specificity of the test at several cut-off values.

Mentions: Synovial overexpression of IL-7R is associated with poor response to TNF blockade in DMARD-resistant RA patients [6]. We therefore wondered whether baseline serum sIL-7R levels would have the same informative value about response to TNF blocking therapy in RA. Strikingly, in patients displaying active disease despite DMARD therapy and subsequently treated with TNF blockade, elevated baseline sIL-7R serum levels strongly predicted poor response to anti-TNF therapy (Fig. 4A, B and C). A total of 55.5% of non-responders to infliximab therapy had an abnormal sIL-7R value at baseline, versus 15.3% of the responders. Conversely, normal baseline sIL-7R serum levels were associated with adequate response to therapy, with a sensitivity of 93% and a specificity of 56%. In case of low sIL-7R serum titres, patients have a 87% probability of being responders (predictive positive value); by contrast, in case of elevated sIL-7R serum levels, patients have a 71% probability of being non-responders (predictive negative value).


Rheumatoid arthritis synovial fibroblasts produce a soluble form of the interleukin-7 receptor in response to pro-inflammatory cytokines.

Badot V, Durez P, Van den Eynde BJ, Nzeusseu-Toukap A, Houssiau FA, Lauwerys BR - J. Cell. Mol. Med. (2011)

sIL-7R serum concentrations predict response to TNF blockade in RA. (A) sIL-7R titres measured by sandwich ELISA in duplicate baseline serum samples obtained in DMARD-resistant RA patients treated with 3 mg/kg infliximab. Patients were categorized in good-responders (circles), moderate- (triangles) and non-responders (squares) according to EULAR response criteria. The horizontal bar depicts the median value in each group. (B) Linear correlation between baseline sIL-7R serum levels and DAS-Score differences (follow-up minus baseline DAS28-CRP). (C) Receiving operating characteristic curve evaluating the value of baseline sIL-7R in predicting response to therapy. The curve was plotted by calculating sensitivity and specificity of the test at several cut-off values.
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Related In: Results  -  Collection

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fig04: sIL-7R serum concentrations predict response to TNF blockade in RA. (A) sIL-7R titres measured by sandwich ELISA in duplicate baseline serum samples obtained in DMARD-resistant RA patients treated with 3 mg/kg infliximab. Patients were categorized in good-responders (circles), moderate- (triangles) and non-responders (squares) according to EULAR response criteria. The horizontal bar depicts the median value in each group. (B) Linear correlation between baseline sIL-7R serum levels and DAS-Score differences (follow-up minus baseline DAS28-CRP). (C) Receiving operating characteristic curve evaluating the value of baseline sIL-7R in predicting response to therapy. The curve was plotted by calculating sensitivity and specificity of the test at several cut-off values.
Mentions: Synovial overexpression of IL-7R is associated with poor response to TNF blockade in DMARD-resistant RA patients [6]. We therefore wondered whether baseline serum sIL-7R levels would have the same informative value about response to TNF blocking therapy in RA. Strikingly, in patients displaying active disease despite DMARD therapy and subsequently treated with TNF blockade, elevated baseline sIL-7R serum levels strongly predicted poor response to anti-TNF therapy (Fig. 4A, B and C). A total of 55.5% of non-responders to infliximab therapy had an abnormal sIL-7R value at baseline, versus 15.3% of the responders. Conversely, normal baseline sIL-7R serum levels were associated with adequate response to therapy, with a sensitivity of 93% and a specificity of 56%. In case of low sIL-7R serum titres, patients have a 87% probability of being responders (predictive positive value); by contrast, in case of elevated sIL-7R serum levels, patients have a 71% probability of being non-responders (predictive negative value).

Bottom Line: We found that exposure of RA FLS to pro-inflammatory cytokines (TNF-α, IL-1β and combinations of TNF-α and IL-1β or TNF-α and IL-17) induces sIL-7R secretion.In DMARD-resistant patients, high sIL-7R serum concentrations are strongly associated with poor response to TNF-blockade.In conclusion, sIL-7R is induced by pro-inflammatory cytokines in RA FLS. sIL-7R could qualify as a new biomarker of response to therapy in RA.

View Article: PubMed Central - PubMed

Affiliation: Rheumatology Department, Cliniques Universitaires Saint-Luc, Université catholique de Louvain, Brussels, Belgium.

Show MeSH
Related in: MedlinePlus