Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
Analysis of Vascular Endothelium from Female Systemic Lupus Erythematosus (SLE) Patients Identifies an Interferon Signature That Correlates with Disease Activity.
Goldenberg3, Diana, Olferiev3, Mikhail, Onat1, Duygu, Andrade3, Danieli, Crow3, Mary K., Colombo1, Paolo C., Salmon2, Jane E.
Accelerated atherosclerosis has emerged as a significant threat to the health of patients with systemic lupus erythematosus (SLE). Endothelial dysfunction represents an important precursor to the development of atherosclerosis. The type I interferons likely influence the relationship between endothelial dysfunction and vascular health in lupus patients. To study the pathogenesis of endothelial dysfunction in SLE, we utilized a novel, minimally-invasive approach to sample venous endothelial cells (ECs) and perform gene expression profiling.
Venous endothelial cells were sampled from 11 adult SLE patients and 10 healthy controls. ECs were collected from arm veins using endovascular wires. ECs were purified; amplified RNA was hybridized with Affymetrix HG-U133 2.0. Samples were normalized to the baseline median level according to the RMA algorithm. Data was analyzed using GeneSpring GX 11 software. Student T test analysis for multiple samples was performed. Differentially expressed genes with >2.0 fold expression and p<0.05 were selected. SLE disease activity was assessed by SLEDAI at the time of endothelial sampling. The interferon score was determined using the mean of the normalized expression values for IFIT1, IFIT3, MX2 and OAS2. To simulate our in vivo findings and to determine whether SLE serum could directly alter endothelial cell gene profiles, we cultured HUVECs with sera from SLE patients and healthy controls and assessed their capacity to induce interferon-inducible genes, IFIT1, IFI44 and MX1 using Real-time quantitative polymerase chain reaction.
Eleven (8 females, 3 males) adult SLE patients meeting American College of Rheumatology criteria for SLE and 10 age-matched controls were studied. Their mean age was 32.2 ± 10.2 yrs, mean SLEDAI score was 6.82; range 020. Ten age-matched healthy subjects were studied. A total of 2013 known genes were differentially expressed (FC >=2, p<0.05) between all SLE patients and controls while 183 known genes were differentially expressed (FC >=2, p<0.05) between female SLE patients and matched controls. IFIT1 and IFIT3 were upregulated in the 11 SLE patients compared with controls. In female SLE patients the interferon signature was particularly robust: IFIT1, IFIT3, MX2 and OAS2 were upregulated. The interferon score correlated significantly with SLEDAI in female patients (R=0.75, p = 0.04). Similar to the results of our in vivo venous endothelial samples, HUVECs cultured with sera from SLE patients showed increased expression of the interferon inducible genes compared with those exposed to sera from control patients (109.1 ± 41.42 vs 0.04 ± 0.01).
Microarray analysis of primary venous endothelial cells distinguished SLE patients from healthy controls based on the expression of interferon-inducible genes. In the 8 female SLE patients, SLE disease activity correlated with the interferon score. These results support the possibility that interferon contributes to the pathogenesis of endothelial dysfunction in SLE patients.
To cite this abstract, please use the following information:
Goldenberg, Diana, Olferiev, Mikhail, Onat, Duygu, Andrade, Danieli, Crow, Mary K., Colombo, Paolo C., et al; Analysis of Vascular Endothelium from Female Systemic Lupus Erythematosus (SLE) Patients Identifies an Interferon Signature That Correlates with Disease Activity. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1183