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- Langefeld, Carl D., et al.
(författare)
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Transancestral mapping and genetic load in systemic lupus erythematosus
- 2017
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Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Systemic lupus erythematosus (SLE) is an autoimmune disease with marked gender and ethnic disparities. We report a large transancestral association study of SLE using Immunochip genotype data from 27,574 individuals of European (EA), African (AA) and Hispanic Amerindian (HA) ancestry. We identify 58 distinct non-HLA regions in EA, 9 in AA and 16 in HA (similar to 50% of these regions have multiple independent associations); these include 24 novel SLE regions (P < 5 x 10(-8)), refined association signals in established regions, extended associations to additional ancestries, and a disentangled complex HLA multigenic effect. The risk allele count (genetic load) exhibits an accelerating pattern of SLE risk, leading us to posit a cumulative hit hypothesis for autoimmune disease. Comparing results across the three ancestries identifies both ancestry-dependent and ancestry-independent contributions to SLE risk. Our results are consistent with the unique and complex histories of the populations sampled, and collectively help clarify the genetic architecture and ethnic disparities in SLE.
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- Elbagir, Sahwa, et al.
(författare)
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Elevated IgA antiphospholipid antibodies in healthy pregnant women in Sudan but not Sweden, without corresponding increase in IgA anti-β2 glycoprotein I domain 1 antibodies
- 2020
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Ingår i: Lupus. - : SAGE Publications. - 0961-2033 .- 1477-0962. ; 29:5, s. 463-473
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The role of antiphospholipid antibodies (aPL) during apparently normal pregnancy is still unclear. IgA aPL are prevalent in populations of African origin. Our aim was to measure all isotypes of anticardiolipin (anti-CL) and anti–β2 glycoprotein I (anti-β2GPI) in healthy pregnant and non-pregnant women of different ethnicities.Methods: Healthy Sudanese pregnant women (n = 165; 53 sampled shortly after delivery), 96 age-matched Sudanese female controls and 42 healthy pregnant and 249 non-pregnant Swedish women were included. IgA/G/M anti-CL and anti-β2GPI were tested at one time point only with two independent assays in Sudanese and serially in pregnant Swedes. IgA anti-β2GPI domain 1 and as controls IgA/G/M rheumatoid factor (RF), IgG anti–cyclic citrullinated peptide 2 (anti-CCP2) and anti–thyroid peroxidase (anti-TPO) were investigated in Sudanese females.Results: Pregnant Sudanese women had significantly higher median levels of IgA anti-CL, IgA anti-β2GPI (p < 0.0001 for both antibodies using two assays) and IgM anti-β2GPI (both assays; p < 0.0001 and 0.008) compared with non-pregnant Sudanese. IgA anti-CL and anti-β2GPI occurrence was increased among Sudanese pregnant women compared with national controls. No corresponding increase during pregnancy was found for IgA anti-β2GPI domain 1 antibodies. Both IgG anti-CL and IgG control autoantibodies decreased during and directly after pregnancy among Sudanese. Serially followed Swedish women showed no changes in IgA aPL, whereas IgG/M anti-CL decreased.Conclusions: IgA aPL are increased in Sudanese but not in Swedish women, without corresponding increase in IgA domain 1. Whether due to ethnicity and/or environmental influences the occurrence of IgA aPL during Sudanese pregnancies, and its clinical significance, is yet to be determined.
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| 8. |
- Abelson, Anna-Karin, et al.
(författare)
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No evidence of association between genetic variants of the PDCD1 ligands and SLE
- 2007
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Ingår i: Genes and Immunity. - : Springer Science and Business Media LLC. - 1466-4879 .- 1476-5470. ; 8:1, s. 69-74
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Tidskriftsartikel (refereegranskat)abstract
- PDCD1, an immunoreceptor involved in peripheral tolerance has previously been shown to be genetically associated with systemic lupus erythematosus (SLE). PDCD1 has two ligands whose genes are located in close proximity on chromosome 9p24. Our attention was drawn to these ligands after finding suggestive linkage to a marker (gata62f03, Z=2.27) located close to their genes in a genome scan of Icelandic families multiplex for SLE. Here, we analyse Swedish trios (N=149) for 23 single nucleotide polymorphisms (SNPs) within the genes of the PDCD1 ligands. Initially, indication of association to eight SNPs was observed, and these SNPs were therefore also analysed in Mexican trios (N=90), as well as independent sets of patients and controls from Sweden (152 patients, 448 controls) and Argentina (288 patients, 288 controls). We do not find support for genetic association to SLE. This is the first genetic study of SLE and the PDCD1 ligands and the lack of association in several cohorts implies that these genes are not major risk factors for SLE.
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- Checa, A., et al.
(författare)
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Dysregulations in circulating sphingolipids associate with disease activity indices in female patients with systemic lupus erythematosus : a cross-sectional study
- 2017
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Ingår i: Lupus. - : SAGE PUBLICATIONS LTD. - 0961-2033 .- 1477-0962. ; 26:10, s. 1023-1033
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Tidskriftsartikel (refereegranskat)abstract
- Objective The objective of this study was to investigate the association of clinical and renal disease activity with circulating sphingolipids in patients with systemic lupus erythematosus.Methods We used liquid chromatography tandem mass spectrometry to measure the levels of 27 sphingolipids in plasma from 107 female systemic lupus erythematosus patients and 23 controls selected using a design of experiment approach. We investigated the associations between sphingolipids and two disease activity indices, the Systemic Lupus Activity Measurement and the Systemic Lupus Erythematosus Disease Activity Index. Damage was scored according to the Systemic Lupus International Collaborating Clinics damage index. Renal activity was evaluated with the British Island Lupus Activity Group index. The effects of immunosuppressive treatment on sphingolipid levels were evaluated before and after treatment in 22 female systemic lupus erythematosus patients with active disease.Results Circulating sphingolipids from the ceramide and hexosylceramide families were increased, and sphingoid bases were decreased, in systemic lupus erythematosus patients compared to controls. The ratio of C-16:0-ceramide to sphingosine-1-phosphate was the best discriminator between patients and controls, with an area under the receiver-operating curve of 0.77. The C-16:0-ceramide to sphingosine-1-phosphate ratio was associated with ongoing disease activity according to the Systemic Lupus Activity Measurement and the Systemic Lupus Erythematosus Disease Activity Index, but not with accumulated damage according to the Systemic Lupus International Collaborating Clinics Damage Index. Levels of C-16:0- and C-24:1-hexosylceramides were able to discriminate patients with current versus inactive/no renal involvement. All dysregulated sphingolipids were normalized after immunosuppressive treatment.Conclusion We provide evidence that sphingolipids are dysregulated in systemic lupus erythematosus and associated with disease activity. This study demonstrates the utility of simultaneously targeting multiple components of a pathway to establish disease associations.
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- Drosos, GC, et al.
(författare)
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EULAR recommendations for cardiovascular risk management in rheumatic and musculoskeletal diseases, including systemic lupus erythematosus and antiphospholipid syndrome
- 2022
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Ingår i: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 81:6, s. 768-779
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Tidskriftsartikel (refereegranskat)abstract
- To develop recommendations for cardiovascular risk (CVR) management in gout, vasculitis, systemic sclerosis (SSc), myositis, mixed connective tissue disease (MCTD), Sjögren’s syndrome (SS), systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS).MethodsFollowing European League against Rheumatism (EULAR) standardised procedures, a multidisciplinary task force formulated recommendations for CVR prediction and management based on systematic literature reviews and expert opinion.ResultsFour overarching principles emphasising the need of regular screening and management of modifiable CVR factors and patient education were endorsed. Nineteen recommendations (eleven for gout, vasculitis, SSc, MCTD, myositis, SS; eight for SLE, APS) were developed covering three topics: (1) CVR prediction tools; (2) interventions on traditional CVR factors and (3) interventions on disease-related CVR factors. Several statements relied on expert opinion because high-quality evidence was lacking. Use of generic CVR prediction tools is recommended due to lack of validated rheumatic diseases-specific tools. Diuretics should be avoided in gout and beta-blockers in SSc, and a blood pressure target <130/80 mm Hg should be considered in SLE. Lipid management should follow general population guidelines, and antiplatelet use in SLE, APS and large-vessel vasculitis should follow prior EULAR recommendations. A serum uric acid level <0.36 mmol/L (<6 mg/dL) in gout, and disease activity control and glucocorticoid dose minimisation in SLE and vasculitis, are recommended. Hydroxychloroquine is recommended in SLE because it may also reduce CVR, while no particular immunosuppressive treatment in SLE or urate-lowering therapy in gout has been associated with CVR lowering.ConclusionThese recommendations can guide clinical practice and future research for improving CVR management in rheumatic and musculoskeletal diseases.
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Frequency of antibiotic-associated diarrhoea in 2462 antibiotic-treated hospitalized patients : a prospective study
- 2001
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Ingår i: Journal of Antimicrobial Chemotherapy. - : Oxford University Press (OUP). - 0305-7453 .- 1460-2091. ; 47:1, s. 43-50
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Tidskriftsartikel (refereegranskat)abstract
- The frequency of antibiotic-associated diarrhoea (AAD) and Clostridium difficile-associated diarrhoea (CdAD) was prospectively determined in a population of 2462 patients recruited from five Swedish hospitals, including divisions for infectious diseases, orthopaedics, surgery, geriatrics, nephrology and internal medicine. AAD developed in 4.9% of the treated patients. Faecal samples were obtained from 69% of patients with AAD and 55.4% were positive for C. difficile cytotoxin B. The frequency of AAD varied from 1.8 to 6.9% at the participating centres (P < 0.001). The frequency of AAD also varied considerably between medical disciplines and wards within different hospitals and was highest in the nephrology and geriatric units (6.7 and 7.1%, respectively). There was no difference in frequency of AAD when analysed with respect to gender or age. Medical interventions (laxative treatment, endoscopy and abdominal surgery) or presence of one concomitant disease (diabetes, malignancy, chronic renal disease and inflammatory bowel disease) did not significantly affect the frequency of AAD, whereas patients suffering from two or more of these illnesses had significantly (P = 0.001) higher frequencies of AAD. Patients treated with antibiotics for 3 days had a significantly (P = 0.009) lower frequency of AAD than those treated for longer periods. Treatment with cephalosporins, clindamycin or broad-spectrum penicillins was associated with an increased risk of AAD. With specimens from one centre, 62.5% of tested patients with AAD and 33.8% of asymptomatic patients were positive for cytotoxin B. Although C. difficile cytotoxin B in stool samples was significantly associated with AAD IP = 0.003), the causal relationship with diarrhoea is not always evident.
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| 23. |
- Gateva, Vesela, et al.
(författare)
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A large-scale replication study identifies TNIP1, PRDM1, JAZF1, UHRF1BP1 and IL10 as risk loci for systemic lupus erythematosus
- 2009
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 41:11, s. 1228-1233
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies have recently identified at least 15 susceptibility loci for systemic lupus erythematosus (SLE). To confirm additional risk loci, we selected SNPs from 2,466 regions that showed nominal evidence of association to SLE (P < 0.05) in a genome-wide study and genotyped them in an independent sample of 1,963 cases and 4,329 controls. This replication effort identified five new SLE susceptibility loci (P < 5 x 10(-8)): TNIP1 (odds ratio (OR) = 1.27), PRDM1 (OR = 1.20), JAZF1 (OR = 1.20), UHRF1BP1 (OR = 1.17) and IL10 (OR = 1.19). We identified 21 additional candidate loci with P< or = 1 x 10(-5). A candidate screen of alleles previously associated with other autoimmune diseases suggested five loci (P < 1 x 10(-3)) that may contribute to SLE: IFIH1, CFB, CLEC16A, IL12B and SH2B3. These results expand the number of confirmed and candidate SLE susceptibility loci and implicate several key immunologic pathways in SLE pathogenesis.
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