B cell polygenic risk scores associate with anti-dsDNA antibodies and nephritis in systemic lupus erythematosus.
| Autor: | Hedenstedt A; Rheumatology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden., Reid S; Rheumatology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden., Sayadi A; Rheumatology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden., Eloranta ML; Rheumatology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden., Skoglund E; Rheumatology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden., Bolin K; Rheumatology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden., Frodlund M; Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection/Rheumatology, Linköping University, Linkoping, Sweden., Lerang K; Department of Rheumatology, Oslo University Hospital, Oslo, Norway., Jönsen A; Rheumatology, Department of Clinical Sciences, Lund University, Lund, Sweden., Rantapää-Dahlqvist S; Department of Public Health and Clinical Medicine/Rheumatology, Umeå University, Umea, Sweden., Bengtsson AA; Rheumatology, Department of Clinical Sciences, Lund University, Lund, Sweden., Rudin A; Department of Rheumatology and Inflammation Research, University of Gothenburg Sahlgrenska Academy, Gothenburg, Sweden., Molberg Ø; Department of Rheumatology, Oslo University Hospital, Oslo, Norway., Sjöwall C; Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection/Rheumatology, Linköping University, Linkoping, Sweden., Sandling JK; Rheumatology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden., Leonard D; Rheumatology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden Dag.Leonard@medsci.uu.se. |
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| Jazyk: | angličtina |
| Zdroj: | Lupus science & medicine [Lupus Sci Med] 2023 Oct; Vol. 10 (2). |
| DOI: | 10.1136/lupus-2023-000926 |
| Abstrakt: | Objective: B cell function and autoantibodies are important in SLE pathogenesis. In this work, we aimed to investigate the impact of cumulative SLE B cell genetics on SLE subphenotype and autoantibody profile. Methods: Female patients with SLE (n=1248) and healthy controls (n=400) were genotyped using Illumina's Global Screening Array. Two polygenic risk scores (PRSs), one representing B cell genes and the other B cell activation genes, were calculated for each individual using risk loci for SLE in genes assigned to B cell-related pathways according to the Kyoto Encyclopedia of Genes and Genomes, Gene Ontology and Reactome Databases. Results: Double-stranded DNA (dsDNA) antibodies were more prevalent among patients with a high compared with a low SLE B cell PRS (OR 1.47 (1.07 to 2.01), p=0.018), and effect sizes were augmented in patients with human leucocyte antigen (HLA) risk haplotypes HLA-DRB1*03:01 and HLA-DRB1*15:01 (DRB1*03/15 -/- (OR 0.99 (0.56 to 1.77), p=0.98; DRB1*03/15 +/- or -/+ (OR 1.64 (1.06 to 2.54), p=0.028; and DRB1*03/15 +/+ (OR 4.47 (1.21 to 16.47), p=0.024). Further, a high compared with a low B cell PRS was associated with low complement levels in DRB1*03/15 +/+ patients (OR 3.92 (1.22 to 12.64), p=0.022). The prevalence of lupus nephritis (LN) was higher in patients with a B cell activation PRS above the third quartile compared with patients below (OR 1.32 (1.00 to 1.74), p=0.048). Conclusions: High genetic burden related to B cell function is associated with dsDNA antibody development and LN. Assessing B cell PRSs may be important in order to determine immunological pathways influencing SLE and to predict clinical phenotype. Competing Interests: Competing interests: None declared. (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.) |
| Databáze: | MEDLINE |
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