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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Enhanced type I interferon gene signature in primary antiphospholipid syndrome: Association with earlier disease onset and preeclampsia

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Ugolini-Lopes, Michelle Remiao [1] ; Torrezan, Giovana Tardin [2] ; Rossi Gandara, Ana Paula [1] ; Ribeiro Olivieri, Eloisa Helena [2] ; Nascimento, Iana Souza [1] ; Okazaki, Erica [3] ; Bonfa, Eloisa [1] ; Carraro, Dirce Maria [2] ; Oliveira de Andrade, Danieli Castro [1]
Total Authors: 9
[1] Univ Sao Paulo, Fac Med, Rheumatol Div, Sao Paulo - Brazil
[2] AC Camargo Canc Ctr, Lab Genom & Mol Biol, Sao Paulo - Brazil
[3] Univ Sao Paulo, Fac Med, Hematol Div, Sao Paulo - Brazil
Total Affiliations: 3
Document type: Review article
Source: AUTOIMMUNITY REVIEWS; v. 18, n. 4, p. 393-398, APR 2019.
Web of Science Citations: 3

Objective: Recently, two studies demonstrated that a relevant percentage of primary antiphospholipid syndrome (PAPS) patients had an upregulation of interferon (IFN) genes. However, 20%-28% of these patients had anti-dsDNA, a highly specific systemic lupus erythematosus (SLE) autoantibody. This study aimed to determine the prevalence of the type I IFN signature in the peripheral blood mononuclear cells of PAPS patients without specific SLE autoantibodies and search for its clinical associations. Methods: Fifty-three PAPS patients (Sydney's criteria) were consecutively selected and age-matched with 50 healthy controls. A third group of nonimmune-mediated thrombophilia patients was also included. The expression of 41 IFN-induced genes was analyzed using real time quantitative PCR. A principal component analysis determined which genes composed the IFN signature, and the z-score was calculated. An ROC curve defined the signature cut-off. Results: Six genes remained in the IFN signature DNAJA1, IFIT5, IF127, MX1, IF16, and TYK2. The ROC cutoff was 3.9-fold (AUC = 0.706, S = 0.49, E = 0.86, PPV = 0.79, NPV = 0.61). The type I IFN signature was present in 49% of the patients with PAPS compared with 14.0% of the healthy controls and 17% of the nonimmunemediated thrombophilia patients (p < .0001). The IFN signature was associated with a younger age at the first antiphospholipid syndrome event (p = .023) and with preeclampsia (p = .032). Conclusion: Our results indicate that PAPS patients without lupus-specific antibodies have an enhanced type IFN gene signature that is not observed in nonimmune-mediated thrombophilia. Also, this overexpression of type I IFN-regulated genes associated with an earlier onset of antiphospholipid syndrome event and preeclampsia. (AU)

FAPESP's process: 14/17965-1 - Type I Interferon Signature in Primary Antiphospholipid Syndrome
Grantee:Danieli Castro Oliveira de Andrade
Support type: Regular Research Grants