title: Type I Interferon Gene Response Is Increased in Early and Established Rheumatoid Arthritis and Correlates with Autoantibody Production.
abstract: BACKGROUND
  Rheumatoid arthritis (RA) is an inflammatory debilitating disease that affects the joints in the early and productive phases of an individual's life. Several cytokines have been linked to the disease pathogenesis and are known to contribute to the inflammatory state characteristic of RA. The participation of type I interferon (IFN) in the pathogenesis of the disease has been already described as well as the identity of the genes that are regulated by this molecule, which are collectively known as the type I IFN signature. These genes have several functions associated with apoptosis, transcriptional regulation, protein degradation, Th2 cell induction, B cell proliferation, etc. This article evaluated the expression of several genes of the IFN signature in different stages of disease and their correlation with the levels of anticitrullinated protein antibodies (ACPA) anticarbamylated protein (Anti-CarP) antibodies.
  
  
  METHODS
  Samples from individuals with early and established RA, high-risk individuals (ACPA+ and ACPA-), and healthy controls were recruited at "Unidad de Artritis y Rheumatismo" (Rheumatism and Arthritis Unit) in Guadalajara Jalisco Mexico. Determinations of ACPA were made with Eurodiagnostica ACPA plus kit. Anti-CarP determinations were made according to previously described protocols. RNA was isolated, and purity and integrity were determined according to RNA integrity number >6. Gene expression analysis was made by RT-qPCR using specific primers for mRNAs of the type I IFN signature. Relative gene expression was calculated according to Livak and Schmitgen.
  
  
  RESULTS
  Significant differences in gene expression were identified when comparing the different groups forMXAandMXB(P< 0.05), also when comparing established RA and ACPA- in both IFIT 1 andG15. An increased expression ofISG15was identified (P< 0.05), and a clear tendency toward increase was identified forHERC5.EPSTRI1, IFI6, andIFI35were found to be elevated in the chronic/established RA and early RA (P< 0.05). Significant correlations were identified for the IFN signature genes with the levels of ACPA and anti-CarP (P< 0.05).
  
  
  CONCLUSIONS
  Our data confirm previous observations in the role of IFN signature and the pathogenesis of RA. Also, we provide evidence of an association between several genes of the IFN signature (that regulate Th2 cells and B cell proliferation) with the levels of anti-CarP antibodies and ACPA.
authors.affiliation: Medical research Unit of Zacatecas, Mexican Institute of Social Security, UIMZ-IMSS, Zacatecas, Mexico; National Council of Science and Technology, CONACYT, Catedras-CONACYT, Zacatecas, Mexico.
authors.forename: Julio E
authors.initials: JE
authors.lastname: Castañeda-Delgado
authors.affiliation: Medical research Unit of Zacatecas, Mexican Institute of Social Security, UIMZ-IMSS, Zacatecas, Mexico; National Council of Science and Technology, CONACYT, Catedras-CONACYT, Zacatecas, Mexico.
authors.forename: Yadira
authors.initials: Y
authors.lastname: Bastián-Hernandez
authors.affiliation: Medical research Unit of Zacatecas, Mexican Institute of Social Security, UIMZ-IMSS, Zacatecas, Mexico; Departamento de fisiología y farmacología, centro de ciencias básicas, Universidad Autónoma de Aguascalientes, Aguascalientes, Aguascalientes, Mexico.
authors.forename: Noe
authors.initials: N
authors.lastname: Macias-Segura
authors.affiliation: Medical research Unit of Zacatecas, Mexican Institute of Social Security, UIMZ-IMSS , Zacatecas , Mexico.
authors.forename: David
authors.initials: D
authors.lastname: Santiago-Algarra
authors.affiliation: Unidad de Investigación en Enfermedades Crónico-Degenerativas , Guadalajara, Jalisco , México.
authors.forename: Jose D
authors.initials: JD
authors.lastname: Castillo-Ortiz
authors.affiliation: Medical research Unit of Zacatecas, Mexican Institute of Social Security, UIMZ-IMSS , Zacatecas , Mexico.
authors.forename: Ana L
authors.initials: AL
authors.lastname: Alemán-Navarro
authors.affiliation: General Hospital: "Emilio Varela Lujan", Mexican Institute of Social Security, IMSS , Zacatecas , Mexico.
authors.forename: Pedro
authors.initials: P
authors.lastname: Martínez-Tejada
authors.affiliation: Medical research Unit of Zacatecas, Mexican Institute of Social Security, UIMZ-IMSS , Zacatecas , Mexico.
authors.forename: Leonor
authors.initials: L
authors.lastname: Enciso-Moreno
authors.affiliation: Medical research Unit of Zacatecas, Mexican Institute of Social Security, UIMZ-IMSS , Zacatecas , Mexico.
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Garcia-De Lira
authors.affiliation: Medical research Unit of Zacatecas, Mexican Institute of Social Security, UIMZ-IMSS , Zacatecas , Mexico.
authors.forename: Diana
authors.initials: D
authors.lastname: Olguín-Calderón
authors.affiliation: Department of Rheumatology, Leiden University Medical Center , Leiden , Netherlands.
authors.forename: Leendert A
authors.initials: LA
authors.lastname: Trouw
authors.affiliation: Universidad Autonoma de Guadalajara , Jalisco , México.
authors.forename: Cesar
authors.initials: C
authors.lastname: Ramos-Remus
authors.affiliation: Medical research Unit of Zacatecas, Mexican Institute of Social Security, UIMZ-IMSS , Zacatecas , Mexico.
authors.forename: Jose A
authors.initials: JA
authors.lastname: Enciso-Moreno
keywords: anticarbamylated protein; anticitrullinated protein antibodies; biomarkers; interferon-1 signature; rheumatoid arthritis