RESEARCH - Proteomic analysis of secreted proteins in early RA

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Ann Rheum Dis. 2006 Aug 10; [Epub ahead of print]

Proteomic analysis of secreted proteins in early rheumatoid arthritis:

Anti-citrulline reactivity is associated with upregulation of

proinflammatory cytokines.

Hueber W, Tomooka BH, Zhao X, Kidd BA, Drijfhout JW, Fries JF, Van Venrooij

WJ, Metzger AL, Genovese MC, WH.

Stanford University and GRECC, Veterans Affairs Palo Alto Health Care

System, United States.

OBJECTIVES: We applied arthritis antigen microarrays and a multiplex

cytokine assay to identify peripheral blood autoantibody and cytokine

profiles that characterise clinically-relevant subgroups of patients with

early rheumatoid arthritis (RA). METHODS: Serum samples from 56 patients

with a diagnosis of RA of < 6 month's duration were tested. Cytokine

profiles were also determined in samples from patients with psoriatic

arthritis and ankylosing spondylitis (PsA/AS, n = 21), and healthy

individuals (n = 19). Data were analysed using Kruskal-Wallis tests with

Dunn's adjustment for multiple comparisons, linear correlation tests,

significance analysis of microarrays (SAM), and hierarchical clustering

software. RESULTS: Distinct antibody profiles were associated with subgroups

of patients who exhibited high serum levels of TNFalpha, IL-1beta, IL-6,

IL-13, IL-15 and GM-CSF. We observed significantly increased autoantibody

reactivity against citrullinated epitopes in patients within the cytokine

high subgroup. Elevated levels of TNF, IL-1alpha, IL-12p40 and IL-13, and

the chemokines eotaxin/CCL11, MCP-1/CCL2 and IP-10/CXCL10 were present in

early RA as compared to control patients (p < 0.0001). Chemokines

demonstrated some of the most impressive differences. Only IL-8/CXCL8

concentrations were higher in PsA/AS patients (p = 0.02).

CONCLUSIONS: Elevated blood levels of proinflammatory cytokines are

associated with autoantibody targeting of citrullinated antigens and

surrogate markers of disease activity in patients with early RA. Proteomic

analysis of serum autoantibodies, cytokines and chemokines enables

stratification of early RA patients into molecular subgroups.

PMID: 16901957

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

6901957 & dopt=Abstract

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