Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement
The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.
Gene Signatures That Predict Development of Arthritis
Van Baarsen1, Lisa G.M., Bos2, Wouter H., Rustenburg1, Francois, van der Pouw Kraan1, Tineke C.T.M., Wolbink2, Gertjan., Dijkmans3, Ben A.C., van Schaardenburg2, Dirkjan
Recognition of the preclinical phase of rheumatoid arthritis (RA) allows a timely start of treatment with the ultimate goal of primary prevention. We aimed to identify molecular features that are associated with the development of RA in order to understand the pathophysiology of preclinical development and to assign predictive biomarkers.
In total, 25 RA patients and 109 ACPA and/or RF positive arthralgia patients at risk for RA and with definitive absence of arthritis (swollen joint count [SJC]=0) in 44 joints at physical examination at the baseline visit determined by two experienced rheumatologists, were included in this study. Exclusion criteria for the arthralgia group were: the presence of recent infections, autoimmune rheumatic diseases, cancer, arthritis revealed by chart review or baseline physical examination, erosions on hand or feet X-ray examination and previous treatment with DMARD or corticosteroids. Gene expression profiles of blood samples were determined by DNA microarray analysis and qPCR. Significance Analysis of Microarrays (SAM) was used to determine significantly differential expressed genes. PANTHER Classification System was used to interpret our data. Cox-regression hazard analysis assessed the relative risk for arthritis development in subgroups of autoantibody positive arthralgia patients.
Gene expression profiling of peripheral blood cells revealed molecular heterogeneity among autoantibody positive arthralgia patients at risk for arthritis development based on differential expression of genes that are involved in diverse arms of the immune response. Interim analysis revealed that 20 at risk patients have developed arthritis after a median of 7 months (IQR 415; median follow-up of all patients is 30 [IQR 2239] months) in a median of 3 joints (IQR 35). Here, we report for the first time gene signatures relevant to development of arthritis. Signatures significantly associated with arthritis development (HR 4.5; 95% C.I. 1.315.4; P=0.016) involved IFN-mediated immunity, hematopoiesis and cytokine activity. These processes were reminiscent of those present in RA patients, implying that the preclinical phase of disease already carries features of established disease. Genes involved in B-cell immunology were associated with protection from progression to arthritis.
Our results imply that, IFN-mediated immunity, hematopoiesis and cell trafficking specify the processes relevant to progression to arthritis besides autoantibody positivity. These findings strongly suggest that gene signatures have predictive value for progression to arthritis, which will pave the way to preventive medicine.
To cite this abstract, please use the following information:
Van Baarsen, Lisa G.M., Bos, Wouter H., Rustenburg, Francois, van der Pouw Kraan, Tineke C.T.M., Wolbink, Gertjan., Dijkmans, Ben A.C., et al; Gene Signatures That Predict Development of Arthritis [abstract]. Arthritis Rheum 2009;60 Suppl 10 :2065