ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 2764

Gene Expression Profile in Monocytes of Antiphospholipid Syndrome Patients Reveals Novel Altered Genes and Pathways Involved in the Pathophysiology of the Disease

Patricia Ruiz-Limon1, Carlos Perez-Sanchez2, Maria Ángeles Aguirre Zamorano2, Irene Cecchi3, Nuria Barbarroja2, Yolanda Jiménez-Gómez2, Ivan Arias de la Rosa1, Maria Carmen Abalos-Aguilera1, Pedro Segui4, Eduardo Collantes-Estévez2, Maria Jose Cuadrado5 and Chary Lopez-Pedrera2, 1Rheumatology Service, IMIBIC/Reina Sofia Hospital/University of Cordoba, Cordoba, Spain, 2Rheumatology service, IMIBIC/Reina Sofia Hospital/University of Cordoba, Cordoba, Spain, 3Center of Research of Immunopathology and Rare Diseases- Coordinating Center of Piemonte and Valle d’Aosta Network for Rare Diseases, Department of Clinical and Biological Sciences, University of Turin, Italy, Turin, Italy, 4Radiology, IMIBIC/Reina Sofia Hospital/University of Cordoba, Cordoba, Spain, 5St Thomas Hospital, Lupus Research Unit, London, United Kingdom

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords: ,

Session Information

Date: Tuesday, November 7, 2017

Title: Antiphospholipid Syndrome

Session Type: ACR Concurrent Abstract Session

Session Time: 2:30PM-4:00PM

Background/Purpose: Monocytes are key players involved in the development of several autoimmune disease due to their capacity to modulate lipid metabolism, secrete inflammatory cytokines, chemokines, tissue factor, proteases and reactive oxygen species. However their specific molecular profile of activation in the pathogenesis of Antiphopholipid syndrome patients (APS) has not been yet evaluated. Thus, the aim of this study was to characterize the monocytes molecular signature of altered genes and pathways involved in the pathology of APS patients.

Methods: Monocytes from peripheral blood of six subject including APS and healthy donors (HDs) were purified by negative immunomagnetic selection (Miltenyi). Total RNA was extract and microarray studies were performed in an Agilent G4112F platform (Whole Human Genome Microarray 44k) using the One-Color gene expression system. Functional categorisation of the altered gene signature and molecular pathways and networks, was carried out by using the Ingenuity Pathway Analysis Software (IPA). The most differentially expressed genes were validated by RT-PCR in monocytes purified from 30 APS and 30 HDs. Correlation and association studies were performed with clinical and analytical variables. The effect of antiphospholipid antibodies (aPL) in the expression of a number of genes were also evaluated by in vitro studies on healthy monocytes.

Results: Gene expression array identified 518 significantly altered genes in monocytes from APS patients in relation to the control group (p<0,05 and fold change>2), including 352 up-regulated and 166 down-regulated. IPA analysis showed that the main canonical pathways integrated by these genes were leukocyte adhesion, diapedesis and extravasation signaling (CLDN16, ACTC1, CLDN12, CCL26, CCL23, FPR1 and FPR2), interleukin signaling (IL18, IL12B, IL22RA, NFATC1), IFN, TNF and TFGbeta signaling (IFNAR1, TNFRSF1A, SMAD6), relevant intracellular signaling pathways involved in signal transduction such as p38, Erk, STAT, TLR, JAK and NFkB, and oxidative stress production and antioxidant reponse (GPX8, CYBB, SCLC2A/2,3 and 5). This analysis further identified that the most relevant disease and function in which these altered genes are involved, were leukocyte migration, inflammatory response, cardiovascular disease and free radical scavenging. In addition the alteration of several of these genes was validated by RT-PCR and associated to clinical parameters of all the patients included in the study. In vitro studies demonstrated the specific modulation of several genes by direct effect of aPLs.

Conclusion: Gene expression profile allows the identification of relevant genes and pathways altered in monocytes of APS patients, which are associated with the pathogenesis of the disease and modulated, at least partially, by aPLs. Thus, the identification of novel biomarkers, might contribute to the development of targeted therapies. Acknowledgements: Supported by FIS (PI01333/2015) and CTS-7940.

Disclosure: P. Ruiz-Limon, None; C. Perez-Sanchez, None; M. Á. Aguirre Zamorano, None; I. Cecchi, None; N. Barbarroja, None; Y. Jiménez-Gómez, None; I. Arias de la Rosa, None; M. C. Abalos-Aguilera, None; P. Segui, None; E. Collantes-Estévez, None; M. J. Cuadrado, None; C. Lopez-Pedrera, None.

To cite this abstract in AMA style:

Ruiz-Limon P, Perez-Sanchez C, Aguirre Zamorano MÁ, Cecchi I, Barbarroja N, Jiménez-Gómez Y, Arias de la Rosa I, Abalos-Aguilera MC, Segui P, Collantes-Estévez E, Cuadrado MJ, Lopez-Pedrera C. Gene Expression Profile in Monocytes of Antiphospholipid Syndrome Patients Reveals Novel Altered Genes and Pathways Involved in the Pathophysiology of the Disease [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/gene-expression-profile-in-monocytes-of-antiphospholipid-syndrome-patients-reveals-novel-altered-genes-and-pathways-involved-in-the-pathophysiology-of-the-disease/. Accessed .

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