Anti-beta2GPI-antibody-induced endothelial cell gene expression profiling reveals induction of novel pro-inflammatory genes potentially involved in primary antiphospholipid syndrome.
AuthorsHamid, Colleen G.
Murphy, John J.
MetadataShow full item record
AbstractOBJECTIVE: To determine the effects of primary antiphospholipid syndrome (PAPS)-derived anti-beta(2)GPI antibodies on gene expression in human umbilical vein endothelial cells (HUVEC) by gene profiling using microarrays. METHODS: Anti-beta(2)GPI antibodies purified from sera of patients with PAPS or control IgG isolated from normal subjects were incubated with HUVEC for 4 h before isolation of RNA and processing for hybridisation to Affymetrix Human Genome U133A-2.0 arrays. Data were analysed using a combination of the MAS 5.0 (Affymetrix) and GeneSpring (Agilent) software programmes. For selected genes microarray data were confirmed by real-time PCR analysis or at the protein level by ELISA. RESULTS: A total of 101 genes were found to be upregulated and 14 genes were downregulated twofold or more in response to anti-beta(2)GPI antibodies. A number of novel genes not previously associated with APS were induced, including chemokines CCL20, CXCL3, CX3CL1, CXCL5, CXCL2 and CXCL1, the receptors Tenascin C, OLR1, IL-18 receptor 1, and growth factors CSF2, CSF3 IL-6, IL1beta and FGF18. The majority of downregulated genes were transcription factors/signalling molecules including ID2. Quantitative real-time RT-PCR analysis confirmed the microarray results for selected genes (CSF3, CX3CL1, FGF18, ID2, SOD2, Tenascin C). CONCLUSIONS: This study reveals a complex gene expression response in HUVEC to anti-beta(2)GPI antibodies with multiple chemokines, pro-inflammatory cytokines, pro-thrombotic and pro-adhesive genes regulated by these antibodies in vitro. Some of these newly identified anti-beta(2)GPI antibody-regulated genes could contribute to the vasculopathy associated with this disease.
CitationAnnals of the Rheumatic Diseases, 66 (8): 1000-7
JournalAnnals of the Rheumatic Diseases
- IgG reactivity to phospholipid-bound beta(2)-glycoprotein I is the main determinant of the fraction of lupus anticoagulant activity quenched by addition of hexagonal (II) phase phospholipid in patients with the clinical suspicion of antiphospholipid-antibody syndrome.
- Authors: Safa O, Crippa L, Della Valle P, Sabbadini MG, Viganò D'Angelo S, D'Angelo A
- Issue date: 1999 Sep
- The avidity of anti-beta2-glycoprotein I antibodies in patients with or without antiphospholipid syndrome: a collaborative study in the frame of the European forum on antiphospholipid antibodies.
- Authors: Cucnik S, Kveder T, Ulcova-Gallova Z, Swadzba J, Musial J, Valesini G, Avcin T, Rozman B, Bozic B
- Issue date: 2011 Oct
- The role of β2-glycoprotein I (β2GPI) carbohydrate chains in the reactivity of anti-β2GPI antibodies from patients with primary antiphospholipid syndrome and in the activation and differentiation of U937 cells.
- Authors: Hernández-Ramírez DF, Olivares-Martínez E, Núñez-Álvarez CA, Chavelas EA, García-Hernández E, Gómez-Hernández G, Llorente L, Cabral AR
- Issue date: 2014 Oct 10
- Autoantibodies to beta2-glycoprotein I in systemic lupus erythematosus and primary antiphospholipid antibody syndrome: clinical correlations in comparison with other antiphospholipid antibody tests.
- Authors: Day HM, Thiagarajan P, Ahn C, Reveille JD, Tinker KF, Arnett FC
- Issue date: 1998 Apr
- β2-Glycoprotein-I based peptide regulate endothelial-cells tissue-factor expression via negative regulation of pGSK3β expression and reduces experimental-antiphospholipid-syndrome.
- Authors: Blank M, Baraam L, Eisenstein M, Fridkin M, Dardik R, Heldman Y, Katchalski-Katzir E, Shoenfeld Y
- Issue date: 2011 Aug