Session Information
Date: Monday, November 18, 2024
Title: Vasculitis – Non-ANCA-Associated & Related Disorders Poster III
Session Type: Poster Session C
Session Time: 10:30AM-12:30PM
Background/Purpose: Nephritis is the main cause of long-term morbidity and mortality in patients with Immunoglobulin-A vasculitis (IgAV) [1, 2]. Unfortunately, sensitive, specific, and non-invasive biomarkers are no available for the diagnosis of nephritis and the identification of IgAV patients with a high risk of developing severe renal complications [3]. In this regard, B-cells have been proposed as the main cell type involved in the pathogenesis of IgAV, and preliminary results of our group have pointed to methylation profiles of B-cells as biomarkers of the susceptibility of IgAV. Nevertheless, whether B-cells are also key players in the development of nephritis and could be used as biomarkers of this complication in IgAV is still unknown. Accordingly, the main aim of our study was to determine the role of peripheral B-cells in the renal damage characteristic of IgAV, by performing the first exhaustive analysis of the methylome of peripheral B-cells.
Methods: 29 Caucasian patients with IgAV, who were in the acute phase of the disease, were recruited. Among these patients, 16 (55.2%) developed nephritis. Peripheral blood mononuclear cells were isolated from all the patients by density gradient using Ficol. B-cells were purified using magnetic cell separation by MACS® Technology. Finally, genomic DNA was extracted from each B-cell and bisulfite-converted with the EZ DNA MethylationTM kit and hybridized onto an Infinium MethylationEPIC Bead Chip array.
Results: Our results unveiled profound alterations in the DNA methylation profiles of B-cells between patients with IgAV who developed nephritis and those without this complication. 7656 differentially methylated positions (DMPs) across the whole genome were identified between these groups of individuals. Among them, 7581 were located in one or more genes, whereas the remaining 75 were not associated with any gene (Figure 1). Interestingly, through gene ontology (GO) analysis of these data, we observed an enrichment in several biological processes of the immune response (Figure 2). Moreover, an enrichment in other biological processes, including ganglioside metabolic process, atrial septum primum morphogenesis, and regulation of inositol, among others, was disclosed (Figure 2).
Conclusion: Our results point to the methylation profile of B-cells as a non-invasive biomarker for the diagnosis of renal damage in IgAV.
[1] Autoimmun Rev 2018;17:301-15.; [2] J Am Soc Nephrol 2002;13:1271-8; [3] J Clin Med 2021;10:2310.
Fundings: European Union FEDER funds and “Fondo de Investigaciones Sanitarias” from “Instituto de Salud Carlos III” (ISCIII, Health Ministry, Spain), (PI18/00042 and PI21/00042). JCBL: PFIS program fellowship from the ISCIII, co-funded by the European Social Fund (`Investing in your future´), (FI22/00020). RL-M: Miguel Servet type II program fellowship from the ISCIII, co-funded by ESF (“Investing in your future” (CPII21/00004).
To cite this abstract in AMA style:
Pulito-Cueto V, Batista-Liz J, Terron L, Fernández Rengel I, Sebastián Mora-Gil M, Leonardo M, Peñalba A, Martín-Penagos L, Belmar-Vega L, Gomez-Fernandez C, Gabrie-Rodriguez L, Gálvez Sánchez R, Caminal-Montero L, Turrion Nieves A, Quiroga Colina P, Vicente-rabaneda E, Sevilla-Pérez B, Callejas J, Andrés-León E, Martin J, Marquez A, Castañeda S, Blanco-Alonso R, Lopez-mejias R. The Methylome Profile of B-cells as a Biomarker of Nephritis in IgA Vasculitis [abstract]. Arthritis Rheumatol. 2024; 76 (suppl 9). https://acrabstracts.org/abstract/the-methylome-profile-of-b-cells-as-a-biomarker-of-nephritis-in-iga-vasculitis/. Accessed .« Back to ACR Convergence 2024
ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-methylome-profile-of-b-cells-as-a-biomarker-of-nephritis-in-iga-vasculitis/