Clinical Relevance of Anti-C3 and Anti-C4 Autoantibodies in Lupus Nephritis.
| Autor: | Vasilev V; Clinic of Nephrology, University Hospital - 'Tzaritza Yoanna - ISUL', Medical University of Sofia, Sofia, Bulgaria., Artero MR; Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université de Paris, Team Inflammation, complement and cancer, Paris, France.; Department of Bacteriology and Immunology, Haartman Institute, and Translational Immunology Research Program, University of Helsinki, Helsinki, Finland., Petkova M; Clinic of Nephrology, University Hospital - 'Tzaritza Yoanna - ISUL', Medical University of Sofia, Sofia, Bulgaria., Mihaylova G; Department of Biochemistry, Molecular Medicine and Nutrigenomics, Medical University of Varna, Varna, Bulgaria., Dragon-Durey MA; Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université de Paris, Team Inflammation, complement and cancer, Paris, France.; Laboratoire d'Immunologie, Hôpital Européen Georges Pompidou, APHP, Paris, France; Université de Paris, Paris, France., Radanova M; Department of Biochemistry, Molecular Medicine and Nutrigenomics, Medical University of Varna, Varna, Bulgaria., Roumenina LT; Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université de Paris, Team Inflammation, complement and cancer, Paris, France. |
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| Jazyk: | angličtina |
| Zdroj: | Kidney international reports [Kidney Int Rep] 2024 Feb 02; Vol. 9 (5), pp. 1429-1440. Date of Electronic Publication: 2024 Feb 02 (Print Publication: 2024). |
| DOI: | 10.1016/j.ekir.2024.01.052 |
| Abstrakt: | Introduction: Complement system overactivation is pivotal in lupus nephritis (LN) pathophysiology. Considering that anti-C3 autoantibodies play a significant role in LN pathophysiology, we explored them as disease activity biomarkers and compared them to the ones against the homologous protein, C4. Methods: We investigated the presence of anti-C3 and anti-C4 IgG autoantibodies in a LN cohort ( N = 85 patients) and monitored their changes over time. We correlated autoantibody presence with clinical parameters. We conducted cross-sectional and longitudinal analyses ( N = 295 samples, 8 years follow-up) to explore associations between autoantibodies and disease progression. Antigen-specific anti-C3 or anti-C4 IgG were purified from plasma by affinity chromatography and their reactivity was tested for cross-reactivity against purified C3 or C4 by enzyme-linked immunosorbent assay (ELISA). Results: The reactivity against C3 was independent of C4. Our study revealed distinct roles for anti-C3 and anti-C4 in LN. Anti-C3 IgG exhibited stronger clinical correlations than anti-C4, showing associations with hypocomplementemia, anti-dsDNA, class IV LN, and active disease according to British Isles Lupus Assessment Group (BILAG) renal score. In a longitudinal analysis, anti-C3 positivity at initial sampling predicted present and future disease exacerbation alone and even better when combined with anti-dsDNA, as indicated by a transition to BILAG category A. Conclusion: Our research provides insights into anti-C3/C3b and anti-C4 autoantibodies in LN, revealing that they are often not cross-reactive. Anti-C3 utility as disease activity biomarkers is underscored by its stronger clinical associations and predictive value for future flares. Combining anti-C3 and anti-dsDNA out-performs the 2 factors alone, suggesting that the incorporation of anti-C3/C3b quantification into routine clinical practice could improve LN management. (© 2024 International Society of Nephrology. Published by Elsevier Inc.) |
| Databáze: | MEDLINE |
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