Background/Purpose:

Systemic lupus erythematosus (SLE) is characterized by immune-mediated inflammation in multiple organ systems. SLE, primary Antiphospholipid syndrome (APS) and secondary APS (SAPS) share several clinical features, including atherosclerosis (AT) and cardiovascular disease (CVD), but also have some unique distinguishing characteristics. The aim of this study was to identify shared and differential molecular pathways involved in the pathogenesis of AT and CVD in that autoimmune diseases.

Methods:

127 patients (42 APS, 20 SAPS and 56 SLE) and 61 healthy donors were included. Microarray expression profiling was performed in samples of monocytes from these patients and real time RT-PCR of selected genes was used to validate microarray data. Some clinical and inflammatory parameters were also obtained.

Results:

Comparing to controls, the expression of 555, 1224, and 518 genes were found significantly altered in monocytes from SLE, SAPS, and APS patients, respectively. On the other hand, 1243 genes were differentially regulated in APS vs. SLE, and 605 genes in SAPS vs. SLE. Interestingly, only 220 genes were differentially regulated when comparing APS with SAPS. Approximately 25-30% of the total number of altered genes in the three diseases were related to AT, inflammation and CVD (chemoquines/cytokines and their receptors, molecules related to angiogenesis, oxidative stress, mitochondrial dynamics and metabolism, lipid metabolism and cell to cell signalling). A specific AT/CVD/Inflammation-related gene signature was found for each disease. Thus, compared to LES, APS showed alterations in mitochondria biogenesis and function, oxidative stress and antioxidant defense. Besides the interferon signature found SAPS and SLE patients, a number of genes mediating atherosclerotic/inflammatory signalling were found further altered in SAPS. Multivariate analysis showed that IgG aCL titers, which are known risk factors for AT and CVD events in SLE, independently predicted both atherosclerotic and thrombosis in SAPS. Moreover, a higher percentage of SAPS showed increased carotid intimate media thickness than LES patients. We further found a significant correlation of IgG-aCL titers with circulating levels of inflammatory molecules (tPA, MCP-1, TNFα, and IL-2).

Conclusion:

1) Gene expression profiling allows the segregation of APS, SAPS and SLE, with specific signatures explaining the pro-atherosclerotic, pro-thrombotic and inflammatory changes in these highly related autoimmune diseases. 2) The identification of key genes regulating specific pathophysiologic pathways will permit the development of targeted therapies for each autoimmune condition. Supported by JA0246/2009, P08-CVI-04234, and PS09/01809.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/gene-expression-signatures-in-monocytes-from-primary-antiphospholipd-syndrome-systemic-lupus-erythematosus-and-lupus-with-antiphospholipid-syndrome-identify-specific-pathways-involved-in-the-pathogen/