Cluster of highly expressed interferon-stimulated genes associate more with African ancestry than disease activity in patients with systemic lupus erythematosus. A systematic review of cross-sectional studies

Siddiqi, K. Zahid; Wilhelm, T.; Ulff-Møller, Constance J.; Jacobsen, Søren

doi:10.1016/j.trsl.2021.07.006

Cited by 28 publications

(15 citation statements)

References 79 publications

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“…In AA, we noted no significant association between anti-dsDNA and the IGS, but a significant association with anti-RNP, whereas in EA SLE the association between the IGS and anti-RNP was significantly greater than that of anti-dsDNA and the IGS. This is consistent with a recent report noting an AA-specific IGS, characterised by greater enrichment in AA SLE patients than EA patients and enrichment occurring with lower frequency and magnitude in autoantibody-stratified EA than AA patients 41. It is notable that we found that this subset of the IGS was more frequent in AA SLE, but it appeared to be more related to the presence of anti-RNP antibodies, which were more common in AA.…”

Section: Discussionsupporting

confidence: 93%

“…The GSVA R package was used as a non-parametric, unsupervised gene set enrichment method 37. The inputs for the GSVA algorithm were log2 microarray expression values (Affymetrix Human Transcriptome Array V.2.0) and predefined gene sets describing IFN stimulated gene signatures,15 38–41 TNF38 and interleukin 1 (IL-1) cytokine signatures 15. Probes were filtered out if their IQR was equal to zero.…”

Section: Methodsmentioning

confidence: 99%

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Anti-RNP antibodies are associated with the interferon gene signature but not decreased complement levels in SLE

Hubbard

Pisetsky

Lipsky³

2022

Ann Rheum Dis

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ObjectivesThe goals of these studies were to elucidate the inter-relationships of specific anti-nuclear antibody (ANA), complement, and the interferon gene signature (IGS) in the pathogenesis of systemic lupus erythematosus (SLE).MethodsData from the Illuminate trials were analysed for antibodies to dsDNA as well as RNA-binding proteins (RBP), levels of C3, C4 and various IGS. Statistical hypothesis testing, linear regression analyses and classification and regression trees analysis were employed to assess relationships between the laboratory features of SLE.ResultsInter-relationships of ANAs, complement and the IGS differed between patients of African Ancestry (AA) and European Ancestry (EA); anti-RNP and multiple autoantibodies were more common in AA patients and, although both related to the presence of the IGS, relationships between autoantibodies and complement differed. Whereas, anti-dsDNA had an inverse relationship to C3 and C4, levels of anti-RNP were not related to these markers. The IGS was only correlated with anti-dsDNA in EA SLE and complement was more correlated to the IGS in AA SLE. Finally, autoantibodies occurred in the presence and absence of the IGS, whereas the IGS was infrequent in anti-dsDNA/anti-RBP-negative SLE patients.ConclusionThere is a complex relationship between autoantibodies and the IGS, with anti-RNP associated in AA and both anti-dsDNA and RNP associated in EA. Moreover, there was a difference in the relationship between anti-dsDNA, but not anti-RBP, with complement levels. The lack of a relationship of anti-RNP with C3 and C4 suggests that anti-RNP immune complexes (ICs) may drive the IGS without complement fixation, whereas anti-dsDNA ICs involve complement consumption.

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Section: Discussionsupporting

confidence: 93%

Section: Methodsmentioning

confidence: 99%

Anti-RNP antibodies are associated with the interferon gene signature but not decreased complement levels in SLE

Hubbard

Pisetsky

Lipsky³

2022

Ann Rheum Dis

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“…The present results are consistent with previous findings showing that elevated type I IFN stimulated genes and the development of lupus nephritis were the most prevalent in a population of SLE patients with African ancestry [ 28 ]. Jenks et al showed that there was a disproportionally higher number of African American SLE who developed active disease, nephritis, high anti-Smith, and anti-RNP autoAbs.…”

Section: Discussionsupporting

confidence: 93%

Lupus nephritis correlates with B cell interferon-β, anti-Smith, and anti-DNA: a retrospective study

et al. 2022

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Background In systemic lupus erythematosus (SLE), detection of interferon-β (IFNβ) in B cells was found to be most prominent in patients with high anti-Smith (Sm) and renal disease, but a mechanistic connection was not clear. The objective of the present study is to determine the association of IFNβ in peripheral blood naïve B cells with the histopathological features of lupus nephritis (LN). Methods The percentage of IFNβ+ cells in IgD+CD27− naïve CD19+ B cells (B cell IFNβ) among peripheral blood mononuclear cells (PBMCs) from 80 SLE patients were analyzed using flow cytometry. Serological and clinical data were collected. The correlations of B cell IFNβ with LN classification and with histopathological findings (light, electron, and immunofluorescence [IF] microscopic analyses for deposition of IgM, IgG, IgA, C1q, and C3) were determined in 23 available biopsy specimens. Results B cell IFNβ is positively associated with anti-Sm (p = 0.001), anti-DNA (p = 0.013), and LN (p < 0.001) but was negatively associated with oral/nasal ulcer (p = 0.003) and photosensitivity (p = 0.045). B cell IFNβ positively correlated with immune complex (IC) deposit in the glomerular basement membrane (GBM) (p = 0.002) but not in the mesangial (p = 0.107) or tubular region (p = 0.313). Patients with high B cell IFNβ had statistically increased development of the proliferative LN (Classes III, IV and/or V), compared to patients with low B cell IFNβ (p < 0.0001). Histopathological features positively associated with increased B cell IFNβ included active glomerular lesions as determined by fibrocellular crescents (p = 0.023), chronic glomerular lesions indicated by segmental sclerosis (p = 0.033), and a membranous pattern of renal damage indicated by spike/holes (p = 0.015). Conclusion B cell IFNβ correlates with history of severe LN, glomerular basement membrane (GBM) IC deposition, and anatomical features of both active and chronic glomerular lesions.

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“…The basis for ancestral differences in IFN expression is not well-explained. A study shows that in SLE patients a cluster of highly expressed ISGs including IFI27 is more associated with African ancestry than disease activity ( 32 ). Our study which combines cohorts from ethnically diverse populations (Middle Eastern, Asian, European & South American) shows robust nature of IFI27 as a prognostic biomarker.…”

Section: Discussionmentioning

confidence: 99%

IFI27 transcription is an early predictor for COVID-19 outcomes, a multi-cohort observational study

et al. 2023

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PurposeRobust biomarkers that predict disease outcomes amongst COVID-19 patients are necessary for both patient triage and resource prioritisation. Numerous candidate biomarkers have been proposed for COVID-19. However, at present, there is no consensus on the best diagnostic approach to predict outcomes in infected patients. Moreover, it is not clear whether such tools would apply to other potentially pandemic pathogens and therefore of use as stockpile for future pandemic preparedness.MethodsWe conducted a multi-cohort observational study to investigate the biology and the prognostic role of interferon alpha-inducible protein 27 (IFI27) in COVID-19 patients.ResultsWe show that IFI27 is expressed in the respiratory tract of COVID-19 patients and elevated IFI27 expression in the lower respiratory tract is associated with the presence of a high viral load. We further demonstrate that the systemic host response, as measured by blood IFI27 expression, is associated with COVID-19 infection. For clinical outcome prediction (e.g., respiratory failure), IFI27 expression displays a high sensitivity (0.95) and specificity (0.83), outperforming other known predictors of COVID-19 outcomes. Furthermore, IFI27 is upregulated in the blood of infected patients in response to other respiratory viruses. For example, in the pandemic H1N1/09 influenza virus infection, IFI27-like genes were highly upregulated in the blood samples of severely infected patients.ConclusionThese data suggest that prognostic biomarkers targeting the family of IFI27 genes could potentially supplement conventional diagnostic tools in future virus pandemics, independent of whether such pandemics are caused by a coronavirus, an influenza virus or another as yet-to-be discovered respiratory virus.

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Cluster of highly expressed interferon-stimulated genes associate more with African ancestry than disease activity in patients with systemic lupus erythematosus. A systematic review of cross-sectional studies

Cited by 28 publications

References 79 publications

Anti-RNP antibodies are associated with the interferon gene signature but not decreased complement levels in SLE

Anti-RNP antibodies are associated with the interferon gene signature but not decreased complement levels in SLE

Lupus nephritis correlates with B cell interferon-β, anti-Smith, and anti-DNA: a retrospective study

IFI27 transcription is an early predictor for COVID-19 outcomes, a multi-cohort observational study

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