The association of monocytes and Tregs with disease activity in rheumatoid arthritis

AJ Eakin, T Ahmed, C M McGeough, H Alexander, G D Wright, P V Gardiner, AJ Bjourson, DS Gibson

Research output: Contribution to journalArticle

Abstract

Background Rheumatoid arthritis (RA) is an autoimmune condition characterised by inflamed joints. Disease-modifying anti-rheumatic drugs (DMARD) are ineffective in 30–40% of patients. CD169 (Siglec-1) is expressed by monocytes and correlates with disease activity in RA. It drives pro-inflammatory processes including the suppression of Tregs through its cognate ligand, CD169L. This study aims to define the relationship between CD169, CD169L and disease activity, as a potential early biomarker of treatment response.Methods Peripheral blood mononuclear cells were isolated from healthy controls and RA patients who failed DMARD treatment. FACS was used to: (i) immunophenotype CD169+ monocytes and CD169L+ Tregs, and (ii) assess levels of FoxP3 within Tregs.Results RA patients had a significantly higher percentage of CD169+ monocytes (28.47 ± 7.17, (mean ± SEM), n=19) compared to healthy controls (8.03 ± 1.48, n=19, p=<0.01). A negative correlation was also observed between the percentage of CD169+ monocytes and CD169L+ Tregs in RA patients (r=-0.72, n=19, p=<0.01). Furthermore, the ratio of CD169:CD169L percentages has a positive association with DAS28-ESR (r=0.77, n=9, p=0.02). FoxP3 is expressed at lower levels in RA patients (24.14 ± 1.87, n=25) compared with healthy controls (46.65 ± 6.16, n=13, p=<0.01).Conclusion These results provide preliminary evidence of a relationship between CD169 and CD169L, and further define how their balance is associated with disease activity. Low levels of FoxP3 in RA patients indicates reduced Treg activation, which may cause increased disease activity. We postulate that this balance of cells is key in the immune response and could be used as a surrogate measure of disease activity.
LanguageEnglish
Pages55.12-55.12
JournalJOURNAL OF IMMUNOLOGY
Volume198
Issue number1 Supp
Publication statusPublished - 1 May 2017

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Monocytes
Rheumatoid Arthritis
Antirheumatic Agents
Sialic Acid Binding Ig-like Lectin 1
Blood Cells
Joints
Biomarkers
Ligands
Therapeutics

Keywords

  • Monocytes
  • Tregs
  • Rheumatoid arthritis
  • disease activity
  • biomarker

Cite this

Eakin, AJ., Ahmed, T., McGeough, C. M., Alexander, H., Wright, G. D., Gardiner, P. V., ... Gibson, DS. (2017). The association of monocytes and Tregs with disease activity in rheumatoid arthritis. JOURNAL OF IMMUNOLOGY, 198(1 Supp), 55.12-55.12.
Eakin, AJ ; Ahmed, T ; McGeough, C M ; Alexander, H ; Wright, G D ; Gardiner, P V ; Bjourson, AJ ; Gibson, DS. / The association of monocytes and Tregs with disease activity in rheumatoid arthritis. In: JOURNAL OF IMMUNOLOGY. 2017 ; Vol. 198, No. 1 Supp. pp. 55.12-55.12.
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abstract = "Background Rheumatoid arthritis (RA) is an autoimmune condition characterised by inflamed joints. Disease-modifying anti-rheumatic drugs (DMARD) are ineffective in 30–40{\%} of patients. CD169 (Siglec-1) is expressed by monocytes and correlates with disease activity in RA. It drives pro-inflammatory processes including the suppression of Tregs through its cognate ligand, CD169L. This study aims to define the relationship between CD169, CD169L and disease activity, as a potential early biomarker of treatment response.Methods Peripheral blood mononuclear cells were isolated from healthy controls and RA patients who failed DMARD treatment. FACS was used to: (i) immunophenotype CD169+ monocytes and CD169L+ Tregs, and (ii) assess levels of FoxP3 within Tregs.Results RA patients had a significantly higher percentage of CD169+ monocytes (28.47 ± 7.17, (mean ± SEM), n=19) compared to healthy controls (8.03 ± 1.48, n=19, p=<0.01). A negative correlation was also observed between the percentage of CD169+ monocytes and CD169L+ Tregs in RA patients (r=-0.72, n=19, p=<0.01). Furthermore, the ratio of CD169:CD169L percentages has a positive association with DAS28-ESR (r=0.77, n=9, p=0.02). FoxP3 is expressed at lower levels in RA patients (24.14 ± 1.87, n=25) compared with healthy controls (46.65 ± 6.16, n=13, p=<0.01).Conclusion These results provide preliminary evidence of a relationship between CD169 and CD169L, and further define how their balance is associated with disease activity. Low levels of FoxP3 in RA patients indicates reduced Treg activation, which may cause increased disease activity. We postulate that this balance of cells is key in the immune response and could be used as a surrogate measure of disease activity.",
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Eakin, AJ, Ahmed, T, McGeough, CM, Alexander, H, Wright, GD, Gardiner, PV, Bjourson, AJ & Gibson, DS 2017, 'The association of monocytes and Tregs with disease activity in rheumatoid arthritis', JOURNAL OF IMMUNOLOGY, vol. 198, no. 1 Supp, pp. 55.12-55.12.

The association of monocytes and Tregs with disease activity in rheumatoid arthritis. / Eakin, AJ; Ahmed, T; McGeough, C M; Alexander, H; Wright, G D; Gardiner, P V; Bjourson, AJ; Gibson, DS.

In: JOURNAL OF IMMUNOLOGY, Vol. 198, No. 1 Supp, 01.05.2017, p. 55.12-55.12.

Research output: Contribution to journalArticle

TY - JOUR

T1 - The association of monocytes and Tregs with disease activity in rheumatoid arthritis

AU - Eakin, AJ

AU - Ahmed, T

AU - McGeough, C M

AU - Alexander, H

AU - Wright, G D

AU - Gardiner, P V

AU - Bjourson, AJ

AU - Gibson, DS

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N2 - Background Rheumatoid arthritis (RA) is an autoimmune condition characterised by inflamed joints. Disease-modifying anti-rheumatic drugs (DMARD) are ineffective in 30–40% of patients. CD169 (Siglec-1) is expressed by monocytes and correlates with disease activity in RA. It drives pro-inflammatory processes including the suppression of Tregs through its cognate ligand, CD169L. This study aims to define the relationship between CD169, CD169L and disease activity, as a potential early biomarker of treatment response.Methods Peripheral blood mononuclear cells were isolated from healthy controls and RA patients who failed DMARD treatment. FACS was used to: (i) immunophenotype CD169+ monocytes and CD169L+ Tregs, and (ii) assess levels of FoxP3 within Tregs.Results RA patients had a significantly higher percentage of CD169+ monocytes (28.47 ± 7.17, (mean ± SEM), n=19) compared to healthy controls (8.03 ± 1.48, n=19, p=<0.01). A negative correlation was also observed between the percentage of CD169+ monocytes and CD169L+ Tregs in RA patients (r=-0.72, n=19, p=<0.01). Furthermore, the ratio of CD169:CD169L percentages has a positive association with DAS28-ESR (r=0.77, n=9, p=0.02). FoxP3 is expressed at lower levels in RA patients (24.14 ± 1.87, n=25) compared with healthy controls (46.65 ± 6.16, n=13, p=<0.01).Conclusion These results provide preliminary evidence of a relationship between CD169 and CD169L, and further define how their balance is associated with disease activity. Low levels of FoxP3 in RA patients indicates reduced Treg activation, which may cause increased disease activity. We postulate that this balance of cells is key in the immune response and could be used as a surrogate measure of disease activity.

AB - Background Rheumatoid arthritis (RA) is an autoimmune condition characterised by inflamed joints. Disease-modifying anti-rheumatic drugs (DMARD) are ineffective in 30–40% of patients. CD169 (Siglec-1) is expressed by monocytes and correlates with disease activity in RA. It drives pro-inflammatory processes including the suppression of Tregs through its cognate ligand, CD169L. This study aims to define the relationship between CD169, CD169L and disease activity, as a potential early biomarker of treatment response.Methods Peripheral blood mononuclear cells were isolated from healthy controls and RA patients who failed DMARD treatment. FACS was used to: (i) immunophenotype CD169+ monocytes and CD169L+ Tregs, and (ii) assess levels of FoxP3 within Tregs.Results RA patients had a significantly higher percentage of CD169+ monocytes (28.47 ± 7.17, (mean ± SEM), n=19) compared to healthy controls (8.03 ± 1.48, n=19, p=<0.01). A negative correlation was also observed between the percentage of CD169+ monocytes and CD169L+ Tregs in RA patients (r=-0.72, n=19, p=<0.01). Furthermore, the ratio of CD169:CD169L percentages has a positive association with DAS28-ESR (r=0.77, n=9, p=0.02). FoxP3 is expressed at lower levels in RA patients (24.14 ± 1.87, n=25) compared with healthy controls (46.65 ± 6.16, n=13, p=<0.01).Conclusion These results provide preliminary evidence of a relationship between CD169 and CD169L, and further define how their balance is associated with disease activity. Low levels of FoxP3 in RA patients indicates reduced Treg activation, which may cause increased disease activity. We postulate that this balance of cells is key in the immune response and could be used as a surrogate measure of disease activity.

KW - Monocytes

KW - Tregs

KW - Rheumatoid arthritis

KW - disease activity

KW - biomarker

M3 - Article

VL - 198

SP - 55.12-55.12

JO - J Immunol

T2 - J Immunol

JF - J Immunol

SN - 0022-1767

IS - 1 Supp

ER -

Eakin AJ, Ahmed T, McGeough CM, Alexander H, Wright GD, Gardiner PV et al. The association of monocytes and Tregs with disease activity in rheumatoid arthritis. JOURNAL OF IMMUNOLOGY. 2017 May 1;198(1 Supp):55.12-55.12.