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- Andraos, Rama, et al.
(författare)
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Autoantibodies associated with systemic sclerosis in three autoimmune diseases imprinted by type I interferon gene dysregulation: a comparison across SLE, primary Sjogrens syndrome and systemic sclerosis
- 2022
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Ingår i: Lupus Science and Medicine. - : BMJ PUBLISHING GROUP. - 2053-8790. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveSLE, primary Sjogrens syndrome (pSS) and systemic sclerosis (SSc) are heterogeneous autoimmune diseases with a dysregulated type I interferon (IFN) system. The diseases often show overlapping clinical manifestations, which may result in diagnostic challenges. We asked to which extent SSc-associated autoantibodies are present in SLE and pSS, and whether these link to serum IFN-alpha, clinical phenotypes and sex. Samples with clinical data from patients with SSc and healthy blood donors (HBDs) served as controls. Finally, the diagnostic performance of SSc-associated autoantibodies was evaluated.MethodsSamples from well-characterised subjects with SLE (n=510), pSS (n=116), SSc (n=57) and HBDs (n=236) were analysed using a commercially available immunoassay (EuroLine Systemic Sclerosis Profile (IgG)). IFN-alpha was quantified by ELISA. Self-reported data on Raynauds phenomenon (RP) were available.ResultsWith exceptions for anti-Ro52/SSA and anti-Th/To, SSc-associated autoantibodies were more frequent in SSc than in SLE, pSS and HBDs regardless of sex. IFN-alpha levels correlated with the number of positive SSc-associated autoantibodies (r=0.29, p<0.0001) and associated with Ro52/SSA positivity (p<0.0001). By using data from SLE, SSc and HBDs, RP was significantly associated with topoisomerase I, centromere protein (CENP)-B, RNA polymerase III 11 kDa, RNA polymerase III 155 kDa and PM-Scl100 whereas Ro52/SSA associated inversely with RP. In SLE, CENP-A was associated with immunological disorder, CENP-B with serositis and Ku with lupus nephritis. By combining analysis of ANA (immunofluorescence) with SSc-associated autoantibodies, the diagnostic sensitivity reached 98% and the specificity 33%.ConclusionsThe 13 specificities included in the EuroLine immunoassay are commonly detected in SSc, but they are also frequent among individuals with other diseases imprinted by type I IFNs. These findings are valuable when interpreting serological data on patients with suspected SSc, especially as patients may present with disease manifestations overlapping different rheumatological diseases. In SLE, we observed associations between manifestations and SSc-associated autoantibodies which have not previously been reported.
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- Stockfelt, Marit, et al.
(författare)
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Plasma interferon-alpha protein levels during pregnancy are associated with lower birth weight in systemic lupus erythematosus
- 2024
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Ingår i: Rheumatology. - : OXFORD UNIV PRESS. - 1462-0324 .- 1462-0332.
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Adverse pregnancy outcomes are more common in women with SLE compared with healthy women, but we lack prognostic biomarkers. Plasma IFN-alpha protein levels are elevated in a subgroup of pregnant women with SLE, but whether this is associated with pregnancy outcomes is unknown. We investigated the relationship between IFN-alpha, adverse pregnancy outcomes and the presence of autoantibodies in SLE pregnancy.Methods We followed 76 women with SLE prospectively. Protein levels of IFN-alpha were quantified in plasma collected in the second and third trimester with single-molecule array. Positivity for ANA and aPL antibodies was assessed during late pregnancy with multiplexed bead assay. Clinical outcomes included the adverse pregnancy outcomes small for gestational age (SGA), preterm birth and preeclampsia.Results During SLE pregnancy, women with SGA infants compared with those without had higher levels of plasma IFN-alpha protein, and IFN-alpha positivity was associated with lower birth weight of the infant. Preterm birth was associated with autoantibodies against chromatin. IFN-alpha protein levels associated positively with autoantibodies against chromatin, Smith/RNP (SmRNP) and RNP, but negatively with aPL antibodies.Conclusion Elevated IFN-alpha protein in plasma of women with SLE is a potential risk factor for lower birth weight of their infants. The association between IFN-alpha and lower birth weight warrants further investigation regarding the pathophysiological role of IFN-alpha during SLE pregnancy. Graphical Abstract
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