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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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| 2. |
- Andraos, Rama, et al.
(författare)
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Screening for autoimmune diseases in apparently healthy antinuclear antibody positive individuals
- 2024
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Ingår i: Frontiers in Medicine. - : FRONTIERS MEDIA SA. - 2296-858X. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Background Anti-nuclear antibodies (ANA) assessed by immunofluorescence (IF) microscopy are associated with systemic autoimmune rheumatic diseases (SARD) and can be detected years before onset of clinical symptoms. Recent data indicate dysregulation of the immune system with increased levels of proinflammatory cytokines, including type I interferons (IFN), in ANA-positive versus ANA-negative individuals. Herein, the aims were to investigate IF-ANA, ANA fine specificities, and IFN-alpha protein levels in relation to self-reported symptoms, as well as clinical signs, of SARD in a large group of healthy blood donors (HBD).Methods Sera from 825 HBD (48.8% females) were included. IF-ANA was assessed, using HEp-2 cells, according to the routine at the accredited laboratory of Clinical Immunology, Link & ouml;ping University Hospital. All samples were analyzed for IgG-ANA fine specificities using addressable laser bead assay (ALBIA) at the same laboratory. IFN-alpha was determined using ELISA. Antibody-positive individuals, and their sex- and age-matched antibody-negative controls, were asked to fill a questionnaire regarding symptoms associated with SARD.Results In total, 130 HBD (15.8%) were positive with IF-ANA and/or ALBIA. Anti-U1RNP was significantly more common among women. Generally, self-reported symptoms correlated poorly with IF-ANA and/or ALBIA results. Two females with high levels of Ro60/SSA, Ro52/SSA and IFN-alpha reported mild sicca symptoms and were diagnosed with Sj & ouml;gren's disease after clinical evaluation.Conclusion A considerable proportion of apparently HBD are autoantibody positive, but without clear association to self-reported symptoms. Nevertheless, the combination of autoantibodies, relevant symptoms and high IFN-alpha levels identified the small proportion of individuals with SARD in the study population.
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