Proteomic analysis of secreted proteins in early rheumatoid arthritis: anti-citrulline autoreactivity is associated with up regulation of proinflammatory cytokines

Objectives: To identify peripheral blood autoantibody and cytokine profiles that characterise clinically relevant subgroups of patients with early rheumatoid arthritis using arthritis antigen microarrays and a multiplex cytokine assay. Methods: Serum samples from 56 patients with a diagnosis of rheumatoid arthritis of Results: Distinct antibody profiles were associated with subgroups of patients who exhibited high serum levels of tumour necrosis factor (TNF)α, interleukin (IL)1β, IL6, IL13, IL15 and granulocyte macrophage colony-stimulating factor. Significantly increased autoantibody reactivity against citrullinated epitopes was observed in patients within the cytokine “high” subgroup. Increased levels of TNFα, IL1α, IL12p40 and IL13, and the chemokines eotaxin/CCL11, monocyte chemoattractant protein-1 and interferon-inducible protein 10, were present in early rheumatoid arthritis as compared with controls (p Conclusions: Increased blood levels of proinflammatory cytokines are associated with autoantibody targeting of citrullinated antigens and surrogate markers of disease activity in patients with early rheumatoid arthritis. Proteomic analysis of serum autoantibodies, cytokines and chemokines enables stratification of patients with early rheumatoid arthritis into molecular subgroups.