B cell polygenic risk scores associate with anti-dsDNA antibodies and nephritis in systemic lupus erythematosus
(2023) In Lupus Science and Medicine 10(2).- Abstract
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... (More)
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.
(Less)
- author
- organization
- publishing date
- 2023-10
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Autoantibodies, B cells, Lupus Erythematosus, Systemic, Lupus Nephritis, Polymorphism, Genetic
- in
- Lupus Science and Medicine
- volume
- 10
- issue
- 2
- article number
- e000926
- publisher
- BMJ Publishing Group
- external identifiers
-
- pmid:37844960
- scopus:85175240098
- ISSN
- 2053-8790
- DOI
- 10.1136/lupus-2023-000926
- language
- English
- LU publication?
- yes
- additional info
- P
- id
- 990cb0c8-7339-4377-b393-de248384e284
- date added to LUP
- 2023-12-11 14:35:09
- date last changed
- 2024-04-24 08:04:42
@article{990cb0c8-7339-4377-b393-de248384e284,
abstract = {{<p>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.</p>}},
author = {{Hedenstedt, Anna and Reid, Sarah and Sayadi, Ahmed and Eloranta, Maija Leena and Skoglund, Elisabeth and Bolin, Karin and Frodlund, Martina and Lerang, Karoline and Jönsen, Andreas and Rantapää-Dahlqvist, Solbritt and Bengtsson, Anders A. and Rudin, Anna and Molberg, Øyvind and Sjöwall, Christopher and Sandling, Johanna K. and Leonard, Dag}},
issn = {{2053-8790}},
keywords = {{Autoantibodies; B cells; Lupus Erythematosus, Systemic; Lupus Nephritis; Polymorphism, Genetic}},
language = {{eng}},
number = {{2}},
publisher = {{BMJ Publishing Group}},
series = {{Lupus Science and Medicine}},
title = {{B cell polygenic risk scores associate with anti-dsDNA antibodies and nephritis in systemic lupus erythematosus}},
url = {{http://dx.doi.org/10.1136/lupus-2023-000926}},
doi = {{10.1136/lupus-2023-000926}},
volume = {{10}},
year = {{2023}},
}