RESEARCH - Multicytokine profile is associated with anti-CCP antibodies in early untreated inflammatory polyarthritis

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J Rheumatol. 2004 Dec;31(12):2336-46.

A distinct multicytokine profile is associated with anti-cyclical

citrullinated peptide antibodies in patients with early untreated

inflammatory arthritis.

Hitchon CA, P, Erdile LB, MB, Dozmorov I, Tang Y, Wong K, Centola

M, El-Gabalawy HS.

Arthritis Centre, University of Manitoba, 800 Sherbrook Street, Winnipeg,

Manitoba R3A 1M4, Canada.

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 1beta (IL-1beta),

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-g (IFN-g), CCL2 (monocyte

chemoattractant protein-1, MCP-1), CCL4 (MIP-1beta), and tumor necrosis

factor-a (TNF-a)] were measured in patients with early, untreated

inflammatory arthritis [symptom duration < or = 12 months; > or = 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-1beta), CXCL8 (IL-8), IL-2,

IL-12, IL-17, IL-5, and IL-10 levels, lower IL-6, IFN-g, 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-1beta), IL-13, IL-12, TNF-a, 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.

PMID: 15570632

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve & db=PubMed & list_uids=1\

5570632 & dopt=Abstract

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