Enhanced type I interferon gene signature in primary antiphospholipid syndrome: Association with earlier disease onset and preeclampsia.
Autoimmun Rev
; 18(4): 393-398, 2019 Apr.
Article
em En
| MEDLINE
| ID: mdl-30772492
ABSTRACT
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, IFI27, MX1, IFI6, and TYK2. The ROC cutoff was 3.9-fold (AUCâ¯=â¯0.706, Sâ¯=â¯0.49, Eâ¯=â¯0.86, PPVâ¯=â¯0.79, NPVâ¯=â¯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 nonimmune-mediated thrombophilia patients (pâ¯<â¯.0001). The IFN signature was associated with a younger age at the first antiphospholipid syndrome event (pâ¯=â¯.023) and with preeclampsia (pâ¯=â¯.032).CONCLUSION:
Our results indicate that PAPS patients without lupus-specific antibodies have an enhanced type I 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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pré-Eclâmpsia
/
Interferon Tipo I
/
Síndrome Antifosfolipídica
/
Transcriptoma
Tipo de estudo:
Etiology_studies
/
Observational_studies
/
Prevalence_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
/
Pregnancy
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article