Autoantibodies, complement and type I interferon as biomarkers for personalized medicine in SLE

Biesen, Robert; Rose, Thomas; Hoyer, Bimba F.; Hiepe, Falk

doi:10.1177/0961203316640922

Cited by 18 publications

(8 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although our correlation analysis cannot be confirmed as causality, it clearly highlights the association of the increased expression of Type I IFN response genes with the master regulators of B cell development, and differentiation into plasma cells might be of pivotal importance in the generation of autoantibodies in RA, which has been already described in SLE (76) and some myopathies (77). Further mechanistic studies are needed to confirm such association and describe the detailed mechanism.…”

Section: Discussionmentioning

confidence: 63%

Type I Interferon Gene Response Is Increased in Early and Established Rheumatoid Arthritis and Correlates with Autoantibody Production

et al. 2017

View full text Add to dashboard Cite

BackgroundRheumatoid 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.MethodsSamples 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.ResultsSignificant differences in gene expression were identified when comparing the different groups for MXA and MXB (P < 0.05), also when comparing established RA and ACPA− in both IFIT 1 and G15. An increased expression of ISG15 was identified (P < 0.05), and a clear tendency toward increase was identified for HERC5. EPSTRI1, IFI6, and IFI35 were 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).ConclusionOur 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.

show abstract

Section: Discussionmentioning

confidence: 63%

Type I Interferon Gene Response Is Increased in Early and Established Rheumatoid Arthritis and Correlates with Autoantibody Production

et al. 2017

View full text Add to dashboard Cite

show abstract

“…In SLE, IP-10 was shown to correlate with disease activity cross-sectionally and longitudinally and therefore might be useful as an IFN biomarker in clincial practice in SLE 37. In pSS, IP-10 was shown to be involved in lymphocyte infiltration into glandular tissue of patients with pSS 21.…”

Section: Discussionmentioning

confidence: 99%

“…The upregulation of IP-10 in response to IFN-α and IFN-γ is ∼50-fold higher compared to the upregulation of SIGLEC1. This could speak in favor that IP-10 is more acutely induced during the immune response and might be an explanation why there is a correlation to the flaring and waning disease course in SLE16 37 but not to the chronic disease course in pSS. Moreover, Smiljanovic et al 14 and others showed that SIGLEC1 is mainly upregulated by IFN-α,32 while IP-10 equally responds to IFN-α and IFN-γ 14.…”

Section: Discussionmentioning

confidence: 99%

SIGLEC1 is a biomarker of disease activity and indicates extraglandular manifestation in primary Sjögren's syndrome

et al. 2016

View full text Add to dashboard Cite

ObjectivesTo evaluate the interferon (IFN) biomarkers sialic acid binding Ig like lectin 1 (SIGLEC1, CD169) and IFN-γ-inducible protein-10 (IP-10) in patients with primary Sjögren's syndrome (pSS).Methods31 patients fulfilling the American-European criteria for pSS were included. Disease activity was obtained by EULAR Sjögren's syndrome disease activity index (ESSDAI). SIGLEC1 expression on monocytes was analysed using flow cytometry. IP-10 concentrations were determined using Bioplex human Cytokine 27-plex kit. Spearman rank test (SRT) was used for correlation analysis and Mann-Whitney U (MWU) to test for differences between glandular and extraglandular manifestations.ResultsAn activated IFN system was detected by an upregulation of SIGLEC1 expression in 64.5% and by elevated serum level of IP-10 in 78.9% of our patients with pSS. In a subsequent analysis SIGLEC1 expression was found to be upregulated more frequently in patients with extraglandular manifestations (16/16, 100%) compared to patients with exclusively glandular involvement (4/15, 27%). SIGLEC1 expression could significantly discriminate between these two disease subgroups (p=0.0001, MWU) with a positive predictive value (PPV) of 80% for extraglandular disease. Moreover, the expression correlated with disease activity (p=0.005, r=0.54, SRT). Serum IP-10 levels neither differed significantly between glandular and extraglandular disease nor correlated with ESSDAI.ConclusionsOur results indicate that increased SIGLEC1 expression characterises patients with systemic involvement and high disease activity. Therefore, SIGLEC1 determination might be of value for subset definition, risk stratification and differential therapeutic considerations in pSS.

show abstract

“…This is a low number but could be attributed to disease control, as patients were sampled outside of flares. The differential genes identified in association with SLE patients belonged largely to interferon signaling pathways mediated by pattern recognition receptors; notably, a type I interferon signature has been reported as a potential biomarker for personalized medicine in SLE [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

RNA-Seq Analysis of Gene Expression, Viral Pathogen, and B-Cell/T-Cell Receptor Signatures in Complex Chronic Disease

Bouquet

Gardy

Brown

et al. 2017

Clinical Infectious Diseases

View full text Add to dashboard Cite

show abstract

Autoantibodies, complement and type I interferon as biomarkers for personalized medicine in SLE

Cited by 18 publications

References 63 publications

Type I Interferon Gene Response Is Increased in Early and Established Rheumatoid Arthritis and Correlates with Autoantibody Production

Type I Interferon Gene Response Is Increased in Early and Established Rheumatoid Arthritis and Correlates with Autoantibody Production

SIGLEC1 is a biomarker of disease activity and indicates extraglandular manifestation in primary Sjögren's syndrome

RNA-Seq Analysis of Gene Expression, Viral Pathogen, and B-Cell/T-Cell Receptor Signatures in Complex Chronic Disease

Contact Info

Product

Resources

About