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New Molecular Targets in Systemic Lupus Erythematosus and Lupus Nephritis

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (30 June 2023) | Viewed by 3349

Special Issue Editors


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Guest Editor
Rheumatology and Clinical Immunology Unit, Department of Clinical and Experimental Sciences, ASST Spedali Civili and University of Brescia, 25123 Brescia, Italy
Interests: systemic lupus erythematosus; antiphospholipid syndrome; systemic sclerosis; rheumatoid arthritis; biomarkers; T lymphocytes; autoantibodies; adaptive immunity; bDMARDs

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Guest Editor
Section Head of Rheumatology, Department of Nephrology and Rheumatology, University Medical Center Göttingen, 37075 Göttingen, Germany
Interests: systemic lupus erythematosus; lupus nephritis; sarcoidosis; systemic sclerosis; interstitial lung disease; myositis; vasculitis; emergency medicine
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Special Issue Information

Dear Colleagues,

Systemic lupus erythematosus (SLE), a prototypic autoimmune disease, has seen significant advances over the recent years in terms of molecular pathways involved and a clearer understanding of the pathophysiology. In addition, new molecular targets are being developed and tested, resulting in exciting times for patients and physicians. Nevertheless, many of the developed drugs fail to demonstrate a benefit in subsequent clinical trials. The kidneys are the major organs affected by systemic autoimmune diseases, and lupus nephritis (LN) is one of the most feared complications of SLE, which considerably increasing morbidity and mortality. However, new therapeutic options have emerged with the recent approval of anifrolumab, an anti-interferon antibody, and voclosporine, a novel calcineurin inhibitor. These opportunities come with the challenge of finding their place in the therapeutic algorithms but represent a step forward toward tailoring treatment to individual patients.

This Special Issue aims to provide a forum for new research findings and reviews on the molecular pathways involved in the pathophysiology of SLE and LN, deepening our understanding of this heterogeneous and challenging disease.

We invite basic, translational and clinical scientists from all specialties involved in the research and care of SLE patients to contribute their findings to our themed issue.

Dr. Silvia Piantoni
Dr. Peter Korsten
Guest Editors

Manuscript Submission Information

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Keywords

  • systemic lupus erythematosus
  • lupus nephritis
  • targeted therapies
  • adaptive immunity
  • autoantibodies
  • biomarkers
  • pathophysiology
  • translational research
  • clinical research.

Published Papers (2 papers)

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Research

12 pages, 1028 KiB  
Article
Characterization of Serum Cytokine Profiles of Patients with Active Lupus Nephritis
by Zahrà Rahmé, Chiara Franco, Claudio Cruciani, Federico Pettorossi, Alice Zaramella, Stefano Realdon, Luca Iaccarino, Giulia Frontini, Gabriella Moroni, Andrea Doria, Anna Ghirardello and Mariele Gatto
Int. J. Mol. Sci. 2023, 24(19), 14883; https://doi.org/10.3390/ijms241914883 - 4 Oct 2023
Cited by 1 | Viewed by 1314
Abstract
Cytokines contribute to the pathogenesis of lupus nephritis (LN), yet their value as prognostic biomarkers is still debated. We aimed to describe the serum cytokines’ profiles and prospectively assess correlations with disease features and renal response in a multicentric cohort of consecutive adult [...] Read more.
Cytokines contribute to the pathogenesis of lupus nephritis (LN), yet their value as prognostic biomarkers is still debated. We aimed to describe the serum cytokines’ profiles and prospectively assess correlations with disease features and renal response in a multicentric cohort of consecutive adult patients with biopsy-proven active LN. Cytokine associations with clinical and serological data were performed at LN diagnosis (T0), and at 3 (T3) and 6 months (T6) of follow up. Renal response according to EULAR definition was assessed at T3, T6 and T12. BAFF and interleukin (IL)-37 were measured by ELISA; IL-2, IL-10, IL-17A and IL-18 by a bead-based multiplex cytokine assay (Luminex). Thirty-nine patients with active LN (age 40.5 ± 15.6 years; F 71.8%; 84.6% proliferative LN) were enrolled, of whom twenty-nine displayed complete longitudinal records. At T0, we observed higher levels of IL-37 and IL-17 in proliferative vs. non-proliferative LN (IL-37: 0.0510 (0.0110–0.2300) vs. 0.0000 (0.0000–0.0397) ng/mL, p = 0.0441; IL-17: 2.0920 (0.5125–17.9400) vs. 0.0000 (0.0000–0.6025) pg/mL, p = 0.0026, respectively), and positive correlations between IL-10 and 24 h proteinuria (r = 0.416, p = 0.0249) and anti-dsDNA levels (r = 0.639, p = 0.0003). BAFF was higher in patients with low complement (p < 0.0001). We observed a sustained correlation between BAFF and IL-10 throughout T6 (r = 0.654, p = 0.0210). Higher baseline IL-37 and BAFF levels were associated with renal response at T3 and T6, respectively, while baseline IL-18 levels were higher in patients achieving response at T12. Our study highlights the complexity of the cytokine network and its potential value as a marker of active LN and renal response. Full article
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8 pages, 2187 KiB  
Communication
A Transcriptome Array-Based Approach Links Proteinuria and Distinct Molecular Signatures to Intrarenal Expression of Type I Interferon IFNA5 in Lupus Nephritis
by Peter Korsten and Björn Tampe
Int. J. Mol. Sci. 2023, 24(13), 10636; https://doi.org/10.3390/ijms241310636 - 25 Jun 2023
Cited by 1 | Viewed by 1230
Abstract
In systemic lupus erythematosus (SLE), the relevance of non-hematopoietic sources of type I interferon in human autoimmunity has recently been recognized. Particularly, type I interferon production precedes autoimmunity in early skin lesions related to SLE. However, the relevance of intrarenal type I interferon [...] Read more.
In systemic lupus erythematosus (SLE), the relevance of non-hematopoietic sources of type I interferon in human autoimmunity has recently been recognized. Particularly, type I interferon production precedes autoimmunity in early skin lesions related to SLE. However, the relevance of intrarenal type I interferon expression has not been shown in lupus nephritis. From transcriptome array datasets, median-centered log2 mRNA expression levels of IFNα (IFNA1, IFNA2, IFNA4, IFNA5, IFNA6, IFNA7, IFNA8, IFNA10, IFNA13, IFNA14, IFNA16, IFNA17, and IFNA21), IFNω (IFNW1), and IFNβ (IFNB1) in lupus nephritis were extracted specifically from microdissected tubulointerstitial (n = 32) and glomerular compartments (n = 32). We found an association between proteinuria and tubulointerstitial expression of type I interferon IFNA5 (p = 0.0142), while all others were not significantly associated. By contrast, no such correlation was observed between proteinuria and any type I interferon expression in the glomerular compartment in lupus nephritis. Interestingly, there was no difference between female and male patients (p = 0.8237) and no association between type I interferon IFNA5 expression and kidney function or lupus nephritis progression. Finally, we identified distinct molecular signatures involved in transcriptional regulation (GLI protein-regulated transcription, IRF7 activation, and HSF1-dependent transactivation) and receptor signaling (BMP signaling and GPCR ligand binding) in association with tubulointerstitial expression of type I interferon IFNA5 in the kidney. In summary, this transcriptome array-based approach links proteinuria to the tubulointerstitial expression of type I interferon IFNA5 in lupus nephritis. Because type I interferon receptor subunit I antagonism has recently been investigated in active SLE, the current study further emphasizes the role of type I interferons in lupus nephritis and might also be of relevance for mechanistic studies. Full article
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