Genetic advances in systemic lupus erythematosus: an update

Chen, Lingyan; Morris, David L.; Vyse, Timothy J.

doi:10.1097/bor.0000000000000411

Cited by 120 publications

(94 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“… Illustration of genetic overlap between four musculoskeletal immune‐mediated inflammatory diseases (IMIDs), showing number of gene regions associated across two or more conditions, with gene names listed .…”

Section: Genetic Sharing Between Musculoskeletal Imidsmentioning

confidence: 99%

Genetics of immune-mediated inflammatory diseases

David

Ling

Barton

2018

Clinical and Experimental Immunology

View full text Add to dashboard Cite

Summary Immune‐mediated inflammatory diseases (IMIDs) are characterized by dysregulation of the normal immune response, which leads to inflammation. Together, they account for a high disease burden in the population, given that they are usually chronic conditions with associated co‐morbidities. Examples include systemic lupus erythematosus, rheumatoid arthritis, Crohn's disease and type 1 diabetes. Since the advent of genome‐wide association studies, evidence of considerable genetic overlap in the loci predisposing to a wide range of IMIDs has emerged. Understanding the genetic risk and extent of genetic overlap between IMIDs may help to determine which genes control which aspects of the different diseases; it may identify potential novel therapeutic targets for a number of these conditions, and/or it may facilitate repurposing existing therapies developed originally for different conditions. The findings show that autoantibody‐mediated autoimmune diseases cluster more closely with each other than autoantibody‐negative diseases such as psoriasis, psoriatic arthritis, Crohn's disease and ankylosing spondylitis which, instead, form a seronegative genetic cluster. The genetic clustering largely mirrors the known response to existing biological therapies, but apparent anomalies in treatment response are discussed.

show abstract

Section: Genetic Sharing Between Musculoskeletal Imidsmentioning

confidence: 99%

Genetics of immune-mediated inflammatory diseases

David

Ling

Barton

2018

Clinical and Experimental Immunology

View full text Add to dashboard Cite

show abstract

“…Transfer of human autoantibodies from patients with SLE can cause glomerulonephritis and proteinuria in murine experimental systems,18, 19 emphasizing that they can be pathogenic. Genome‐wide association studies (GWAS) have shown that over 80 loci can contribute to the risk of developing SLE 20. The pathogenesis of the disease is complex, but several broad themes emerge.…”

Section: Slementioning

confidence: 99%

“…Genome-wide association studies (GWAS) have shown that over 80 loci can contribute to the risk of developing SLE. 20 The pathogenesis of the disease is complex, but several broad themes emerge. Multiple genes involved in: (i) the clearance of immune complexes and apoptotic cells; (ii) the regulation of innate immunity, such as the type 1 interferon and complement pathways; and (iii) the regulation of lymphocyte activation and function have been implicated.…”

Section: Slementioning

confidence: 99%

Antibody repertoire analysis in polygenic autoimmune diseases

2018

View full text Add to dashboard Cite

SummaryHigh‐throughput sequencing of the DNA/RNA encoding antibody heavy‐ and light‐chains is rapidly transforming the field of adaptive immunity. It can address key questions, including: (i) how the B‐cell repertoire differs in health and disease; and (ii) if it does differ, the point(s) in B‐cell development at which this occurs. The advent of technologies, such as whole‐genome sequencing, offers the chance to link abnormalities in the B‐cell antibody repertoire to specific genomic variants and polymorphisms. Here, we discuss the current research using B‐cell antibody repertoire sequencing in three polygenic autoimmune diseases where there is good evidence for a pathological role for B‐cells, namely systemic lupus erythematosus, multiple sclerosis and rheumatoid arthritis. These autoimmune diseases exhibit significantly skewed B‐cell receptor repertoires compared with healthy controls. Interestingly, some common repertoire defects are shared between diseases, such as elevated IGHV4‐34 gene usage. B‐cell clones have effectively been characterized and tracked between different tissues and blood in autoimmune disease. It has been hypothesized that these differences may signify differences in B‐cell tolerance; however, the mechanisms and implications of these defects are not clear.

show abstract

“…Genome-wide association studies (GWAS) have been successfully used to investigate the genetic basis of a disease and this has dramatically advanced knowledge of the genetic aetiology of SLE. Our recent review summarized a total of 84 genetic loci that are implicated as SLE risk (11). Despite the advances in the genetics of SLE, it is not clear how to utilise genetic information for the prediction of SLE risk or severity.…”

Section: Introductionmentioning

confidence: 99%

Genome-wide assessment of genetic risk for systemic lupus erythematosus and disease severity

Chen

Wang

Liu

et al. 2019

Preprint

Self Cite

View full text Add to dashboard Cite

Objective: Using three European and two Chinese genome-wide association studies (GWAS), we investigated the performance of genetic risk scores (GRS) for predicting the susceptibility and severity of Systemic lupus erythematosus (SLE), using renal disease as a proxy for severity. Methods:We used four GWASs to test the performance of GRS both cross validating within the European population and between European and Chinese populations. The performance of GRS in SLE risk prediction was evaluated by Receiver Operating Characteristic (ROC) curves. We then analyzed the polygenic nature of SLE statistically. We also partitioned patients according to their age-of-onset and evaluated the predictability of GRS in disease severity in each age group. Results:We found consistently that the best GRS in the prediction of SLE used SNPs associated at the level of P<1e-05 in all GWAS datasets and that SNPs with P-values above 0.2 were inflated for SLE true positive signals. The GRS results in an area under the ROC curve ranging between 0.64 and 0.72, within European and between the European and Chinese populations. We further showed a significant positive correlation between a GRS and renal disease in two independent European GWAS (P cohort1 =2.44e-08; P cohort2 =0.00205) and a significant negative correlation with age of SLE onset (P cohort1 =1.76e-12; P cohort2 =0.00384). We found that the GRS performed better in prediction of renal disease in the 'later onset' compared to the 'earlier onset' group. Conclusion:The GRS predicts SLE in both European and Chinese populations and correlates with poorer prognostic factors: young age of onset and lupus nephritis.

show abstract

Genetic advances in systemic lupus erythematosus: an update

Cited by 120 publications

References 65 publications

Genetics of immune-mediated inflammatory diseases

Genetics of immune-mediated inflammatory diseases

Antibody repertoire analysis in polygenic autoimmune diseases

Genome-wide assessment of genetic risk for systemic lupus erythematosus and disease severity

Contact Info

Product

Resources

About