A distinct multicytokine profile is associated with anti-cyclical citrullinated peptide antibodies in patients with early untreated inflammatory arthritis

Carol A. Hitchon, Philip Alex, Lawrence B. Erdile, Mark B. Frank, Igor Dozmorov, Yuhong Tang, Keng Wong, Michael Centola, Hani S. El-Gabalawy

Research output: Contribution to journalArticle

70 Citations (Scopus)

Abstract

Objective. Early inflammatory arthritis is clinically heterogenous and biologically-based indicators are needed to distinguish severe from self-limited disease. Anti-cyclical citrullinated peptides (CCP) have been identified as potential prognostic markers in early arthritis cohorts. Since cytokine networks are known to play a critical role in the pathogenesis of rheumatoid arthritis (RA) and other forms of inflammatory arthritis, a panel of pro- and antiinflammatory cytokines was measured to identify biologically-based subsets of early arthritis, relating cytokine profiles to clinical measures and to the presence of RA-associated autoantibodies. Methods. Plasma concentrations of cytokines [interleukin 1β (IL-1β), IL-2, IL-4, IL-5, IL-6, IL-7, CXCL8 (IL-8), IL-10, IL-12p70, IL-13, IL-17, granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), interferon-γ (IFN-γ), CCL2 (monocyte chemoattractant protein-1, MCP-1), CCL4 (MIP-1β), and tumor necrosis factor-α (TNF-α)] were measured in patients with early, untreated inflammatory arthritis [symptom duration ≤ 12 months; ≥ 1 swollen joint; RA, n = 41; undifferentiated arthritis (UA), n = 23]. Cytokine expression patterns were determined using cluster analysis. Results. Both pro- and antiinflammatory cytokines were elevated in patients over controls (n = 21). RA clustered into subgroups based solely on cytokine profiles. The "mild" RA subgroup (n = 23) had higher CCL4 (MIP-1β), CXCL8 (IL-8), IL-2, IL-12, IL-17, IL-5, and IL-10 levels, lower IL-6, IFN-γ, GM-CSF, and IL-4 levels, less CCP positivity (52% vs 82%; p < 0.05), and lower CCP titers [71 (78) vs 153 (94); p < 0.01], but similar erythrocyte sedimentation rate, C-reactive protein, and joint counts compared to the "severe" RA groups. CCL4 (MIP-1β), IL-13, IL-12, TNF-α, and IL-4 best distinguished the groups. Combining UA with RA samples preserved cytokine subgroups and strengthened the autoantibody associations. Fewer UA patients in the "mild" cluster (n = 16) were RF-positive (24% vs 100%; p < 0.002) or CCP-positive (24% vs 66%; p < 0.08) compared to the "severe" group. Conclusion. Early untreated inflammatory arthritis can be categorized into distinct subgroups based on cytokine profiles. These subgroups are associated with CCP and RF autoantibodies. Integration of cytokine profiles with autoantibody status may assist prognostication and treatment decisions in these patients.

Original languageEnglish (US)
Pages (from-to)2336-2346
Number of pages11
JournalJournal of Rheumatology
Volume31
Issue number12
StatePublished - Dec 2004

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Arthritis
Cytokines
Peptides
Rheumatoid Arthritis
Antibodies
Autoantibodies
Interleukin-4
Interleukin-7
Interleukin-13
Interleukin-17
Interleukin-5
Interleukin-12
Granulocyte-Macrophage Colony-Stimulating Factor
Interleukin-10
Interferons
Interleukin-2
Interleukin-6
Anti-Inflammatory Agents
Tumor Necrosis Factor-alpha
Joints

Keywords

  • Arthritis
  • Autoantibodies
  • Chemokines
  • Citrulline
  • Cytokines
  • Rheumatoid arthritis

ASJC Scopus subject areas

  • Rheumatology
  • Immunology

Cite this

A distinct multicytokine profile is associated with anti-cyclical citrullinated peptide antibodies in patients with early untreated inflammatory arthritis. / Hitchon, Carol A.; Alex, Philip; Erdile, Lawrence B.; Frank, Mark B.; Dozmorov, Igor; Tang, Yuhong; Wong, Keng; Centola, Michael; El-Gabalawy, Hani S.

In: Journal of Rheumatology, Vol. 31, No. 12, 12.2004, p. 2336-2346.

Research output: Contribution to journalArticle

Hitchon, CA, Alex, P, Erdile, LB, Frank, MB, Dozmorov, I, Tang, Y, Wong, K, Centola, M & El-Gabalawy, HS 2004, 'A distinct multicytokine profile is associated with anti-cyclical citrullinated peptide antibodies in patients with early untreated inflammatory arthritis', Journal of Rheumatology, vol. 31, no. 12, pp. 2336-2346.
Hitchon, Carol A. ; Alex, Philip ; Erdile, Lawrence B. ; Frank, Mark B. ; Dozmorov, Igor ; Tang, Yuhong ; Wong, Keng ; Centola, Michael ; El-Gabalawy, Hani S. / A distinct multicytokine profile is associated with anti-cyclical citrullinated peptide antibodies in patients with early untreated inflammatory arthritis. In: Journal of Rheumatology. 2004 ; Vol. 31, No. 12. pp. 2336-2346.
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abstract = "Objective. Early inflammatory arthritis is clinically heterogenous and biologically-based indicators are needed to distinguish severe from self-limited disease. Anti-cyclical citrullinated peptides (CCP) have been identified as potential prognostic markers in early arthritis cohorts. Since cytokine networks are known to play a critical role in the pathogenesis of rheumatoid arthritis (RA) and other forms of inflammatory arthritis, a panel of pro- and antiinflammatory cytokines was measured to identify biologically-based subsets of early arthritis, relating cytokine profiles to clinical measures and to the presence of RA-associated autoantibodies. Methods. Plasma concentrations of cytokines [interleukin 1β (IL-1β), IL-2, IL-4, IL-5, IL-6, IL-7, CXCL8 (IL-8), IL-10, IL-12p70, IL-13, IL-17, granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), interferon-γ (IFN-γ), CCL2 (monocyte chemoattractant protein-1, MCP-1), CCL4 (MIP-1β), and tumor necrosis factor-α (TNF-α)] were measured in patients with early, untreated inflammatory arthritis [symptom duration ≤ 12 months; ≥ 1 swollen joint; RA, n = 41; undifferentiated arthritis (UA), n = 23]. Cytokine expression patterns were determined using cluster analysis. Results. Both pro- and antiinflammatory cytokines were elevated in patients over controls (n = 21). RA clustered into subgroups based solely on cytokine profiles. The {"}mild{"} RA subgroup (n = 23) had higher CCL4 (MIP-1β), CXCL8 (IL-8), IL-2, IL-12, IL-17, IL-5, and IL-10 levels, lower IL-6, IFN-γ, GM-CSF, and IL-4 levels, less CCP positivity (52{\%} vs 82{\%}; p < 0.05), and lower CCP titers [71 (78) vs 153 (94); p < 0.01], but similar erythrocyte sedimentation rate, C-reactive protein, and joint counts compared to the {"}severe{"} RA groups. CCL4 (MIP-1β), IL-13, IL-12, TNF-α, and IL-4 best distinguished the groups. Combining UA with RA samples preserved cytokine subgroups and strengthened the autoantibody associations. Fewer UA patients in the {"}mild{"} cluster (n = 16) were RF-positive (24{\%} vs 100{\%}; p < 0.002) or CCP-positive (24{\%} vs 66{\%}; p < 0.08) compared to the {"}severe{"} group. Conclusion. Early untreated inflammatory arthritis can be categorized into distinct subgroups based on cytokine profiles. These subgroups are associated with CCP and RF autoantibodies. Integration of cytokine profiles with autoantibody status may assist prognostication and treatment decisions in these patients.",
keywords = "Arthritis, Autoantibodies, Chemokines, Citrulline, Cytokines, Rheumatoid arthritis",
author = "Hitchon, {Carol A.} and Philip Alex and Erdile, {Lawrence B.} and Frank, {Mark B.} and Igor Dozmorov and Yuhong Tang and Keng Wong and Michael Centola and El-Gabalawy, {Hani S.}",
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TY - JOUR

T1 - A distinct multicytokine profile is associated with anti-cyclical citrullinated peptide antibodies in patients with early untreated inflammatory arthritis

AU - Hitchon, Carol A.

AU - Alex, Philip

AU - Erdile, Lawrence B.

AU - Frank, Mark B.

AU - Dozmorov, Igor

AU - Tang, Yuhong

AU - Wong, Keng

AU - Centola, Michael

AU - El-Gabalawy, Hani S.

PY - 2004/12

Y1 - 2004/12

N2 - Objective. Early inflammatory arthritis is clinically heterogenous and biologically-based indicators are needed to distinguish severe from self-limited disease. Anti-cyclical citrullinated peptides (CCP) have been identified as potential prognostic markers in early arthritis cohorts. Since cytokine networks are known to play a critical role in the pathogenesis of rheumatoid arthritis (RA) and other forms of inflammatory arthritis, a panel of pro- and antiinflammatory cytokines was measured to identify biologically-based subsets of early arthritis, relating cytokine profiles to clinical measures and to the presence of RA-associated autoantibodies. Methods. Plasma concentrations of cytokines [interleukin 1β (IL-1β), IL-2, IL-4, IL-5, IL-6, IL-7, CXCL8 (IL-8), IL-10, IL-12p70, IL-13, IL-17, granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), interferon-γ (IFN-γ), CCL2 (monocyte chemoattractant protein-1, MCP-1), CCL4 (MIP-1β), and tumor necrosis factor-α (TNF-α)] were measured in patients with early, untreated inflammatory arthritis [symptom duration ≤ 12 months; ≥ 1 swollen joint; RA, n = 41; undifferentiated arthritis (UA), n = 23]. Cytokine expression patterns were determined using cluster analysis. Results. Both pro- and antiinflammatory cytokines were elevated in patients over controls (n = 21). RA clustered into subgroups based solely on cytokine profiles. The "mild" RA subgroup (n = 23) had higher CCL4 (MIP-1β), CXCL8 (IL-8), IL-2, IL-12, IL-17, IL-5, and IL-10 levels, lower IL-6, IFN-γ, GM-CSF, and IL-4 levels, less CCP positivity (52% vs 82%; p < 0.05), and lower CCP titers [71 (78) vs 153 (94); p < 0.01], but similar erythrocyte sedimentation rate, C-reactive protein, and joint counts compared to the "severe" RA groups. CCL4 (MIP-1β), IL-13, IL-12, TNF-α, and IL-4 best distinguished the groups. Combining UA with RA samples preserved cytokine subgroups and strengthened the autoantibody associations. Fewer UA patients in the "mild" cluster (n = 16) were RF-positive (24% vs 100%; p < 0.002) or CCP-positive (24% vs 66%; p < 0.08) compared to the "severe" group. Conclusion. Early untreated inflammatory arthritis can be categorized into distinct subgroups based on cytokine profiles. These subgroups are associated with CCP and RF autoantibodies. Integration of cytokine profiles with autoantibody status may assist prognostication and treatment decisions in these patients.

AB - Objective. Early inflammatory arthritis is clinically heterogenous and biologically-based indicators are needed to distinguish severe from self-limited disease. Anti-cyclical citrullinated peptides (CCP) have been identified as potential prognostic markers in early arthritis cohorts. Since cytokine networks are known to play a critical role in the pathogenesis of rheumatoid arthritis (RA) and other forms of inflammatory arthritis, a panel of pro- and antiinflammatory cytokines was measured to identify biologically-based subsets of early arthritis, relating cytokine profiles to clinical measures and to the presence of RA-associated autoantibodies. Methods. Plasma concentrations of cytokines [interleukin 1β (IL-1β), IL-2, IL-4, IL-5, IL-6, IL-7, CXCL8 (IL-8), IL-10, IL-12p70, IL-13, IL-17, granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), interferon-γ (IFN-γ), CCL2 (monocyte chemoattractant protein-1, MCP-1), CCL4 (MIP-1β), and tumor necrosis factor-α (TNF-α)] were measured in patients with early, untreated inflammatory arthritis [symptom duration ≤ 12 months; ≥ 1 swollen joint; RA, n = 41; undifferentiated arthritis (UA), n = 23]. Cytokine expression patterns were determined using cluster analysis. Results. Both pro- and antiinflammatory cytokines were elevated in patients over controls (n = 21). RA clustered into subgroups based solely on cytokine profiles. The "mild" RA subgroup (n = 23) had higher CCL4 (MIP-1β), CXCL8 (IL-8), IL-2, IL-12, IL-17, IL-5, and IL-10 levels, lower IL-6, IFN-γ, GM-CSF, and IL-4 levels, less CCP positivity (52% vs 82%; p < 0.05), and lower CCP titers [71 (78) vs 153 (94); p < 0.01], but similar erythrocyte sedimentation rate, C-reactive protein, and joint counts compared to the "severe" RA groups. CCL4 (MIP-1β), IL-13, IL-12, TNF-α, and IL-4 best distinguished the groups. Combining UA with RA samples preserved cytokine subgroups and strengthened the autoantibody associations. Fewer UA patients in the "mild" cluster (n = 16) were RF-positive (24% vs 100%; p < 0.002) or CCP-positive (24% vs 66%; p < 0.08) compared to the "severe" group. Conclusion. Early untreated inflammatory arthritis can be categorized into distinct subgroups based on cytokine profiles. These subgroups are associated with CCP and RF autoantibodies. Integration of cytokine profiles with autoantibody status may assist prognostication and treatment decisions in these patients.

KW - Arthritis

KW - Autoantibodies

KW - Chemokines

KW - Citrulline

KW - Cytokines

KW - Rheumatoid arthritis

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