Anti-beta2GPI-antibody-induced endothelial cell gene expression profiling reveals induction of novel pro-inflammatory genes potentially involved in primary antiphospholipid syndrome.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
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
- Role of the MyD88 transduction signaling pathway in endothelial activation by antiphospholipid antibodies.
- Authors: Raschi E, Testoni C, Bosisio D, Borghi MO, Koike T, Mantovani A, Meroni PL
- Issue date: 2003 May 1
- 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