| 1. |
- Kottyan, Leah C., et al.
(författare)
-
The IRF5-TNPO3 association with systemic lupus erythematosus has two components that other autoimmune disorders variably share.
- 2015
-
Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 24:2, s. 582-596
-
Tidskriftsartikel (refereegranskat)abstract
- Exploiting genotyping, DNA sequencing, imputation and trans-ancestral mapping, we used Bayesian and frequentist approaches to model the IRF5-TNPO3 locus association, now implicated in two immunotherapies and seven autoimmune diseases. Specifically, in systemic lupus erythematosus (SLE), we resolved separate associations in the IRF5 promoter (all ancestries) and with an extended European haplotype. We captured 3230 IRF5-TNPO3 high-quality, common variants across 5 ethnicities in 8395 SLE cases and 7367 controls. The genetic effect from the IRF5 promoter can be explained by any one of four variants in 5.7 kb (P-valuemeta = 6 × 10(-49); OR = 1.38-1.97). The second genetic effect spanned an 85.5-kb, 24-variant haplotype that included the genes IRF5 and TNPO3 (P-valuesEU = 10(-27)-10(-32), OR = 1.7-1.81). Many variants at the IRF5 locus with previously assigned biological function are not members of either final credible set of potential causal variants identified herein. In addition to the known biologically functional variants, we demonstrated that the risk allele of rs4728142, a variant in the promoter among the lowest frequentist probability and highest Bayesian posterior probability, was correlated with IRF5 expression and differentially binds the transcription factor ZBTB3. Our analytical strategy provides a novel framework for future studies aimed at dissecting etiological genetic effects. Finally, both SLE elements of the statistical model appear to operate in Sjögrens syndrome and systemic sclerosis whereas only the IRF5-TNPO3 gene-spanning haplotype is associated with primary biliary cirrhosis, demonstrating the nuance of similarity and difference in autoimmune disease risk mechanisms at IRF5-TNPO3.
|
|
| 2. |
- Jensen, Gert, et al.
(författare)
-
Treatment of iron deficiency in patients with chronic kidney disease : A prospective observational study of iron isomaltoside (NIMO Scandinavia)
- 2019
-
Ingår i: Clinical Nephrology. - : DUSTRI-VERLAG DR KARL FEISTLE. - 0301-0430. ; 91:4, s. 246-253
-
Tidskriftsartikel (refereegranskat)abstract
- Aims: Iron deficiency is common in patients with chronic kidney disease (CKD). Appropriate iron substitution is critical and intravenous iron is an established therapy for these patients. The objective of this study was to assess treatment routine, effectiveness, and safety of iron isomaltoside (Monofer (R), Pharmacosmos A/S, Holbaek, Denmark) in CKD patients in clinical practice.Materials and methods: This was a prospective observational study conducted in predialysis CKD patients treated with iron isomaltoside according to the product label and to routine clinical care.Results: The study included 108 patients with predialysis CKD: 22 were in stage 2 - 3, 41 in stage 4, and 45 in stage 5. The mean (standard deviation) age was 67 (15) years, and 55% of patients were male. The majority of patients (65%) received one iron isomaltoside treatment In patients with a baseline Hb < 10 g/dL, the mean dose of iron isomaltoside in the study was lower than the estimated total iron requirement (567 mg versus 921 mg). A treatment response of Hb >= 1 g/dL was achieved in 16/28 (57%) of patients, and the mean post-treatment Hb level was 10.5 g/dL. The probability of retreatment did not correlate with dose, but no dose administered was > 1,000 mg. There were no serious adverse drug reactions. One nonserious adverse drug reaction - injection site discoloration - was reported, and the patient had an uneventful recovery.Conclusion: Iron isomaltoside shows a good effectiveness and safety profile in predialysis CKD patients. However, some patients did not receive adequate iron doses to allow for optimal correction of their iron deficiency anemia.
|
|
| 3. |
- Norheim, Katrine Brække, et al.
(författare)
-
A possible genetic association with chronic fatigue in primary Sjögren's syndrome : a candidate gene study
- 2014
-
Ingår i: Rheumatology International. - : Springer Science and Business Media LLC. - 0172-8172 .- 1437-160X. ; 34:2, s. 191-197
-
Tidskriftsartikel (refereegranskat)abstract
- Fatigue is prevalent and disabling in primary Sjögren's syndrome (pSS). Results from studies in chronic fatigue syndrome (CFS) indicate that genetic variation may influence fatigue. The aim of this study was to investigate single nucleotide polymorphism (SNP) variations in pSS patients with high and low fatigue. A panel of 85 SNPs in 12 genes was selected based on previous studies in CFS. A total of 207 pSS patients and 376 healthy controls were genotyped. One-hundred and ninety-three patients and 70 SNPs in 11 genes were available for analysis after quality control. Patients were dichotomized based on fatigue visual analogue scale (VAS) scores, with VAS <50 denominated "low fatigue" (n = 53) and VAS ≥50 denominated "high fatigue" (n = 140). We detected signals of association with pSS for one SNP in SLC25A40 (unadjusted p = 0.007) and two SNPs in PKN1 (both p = 0.03) in our pSS case versus control analysis. The association with SLC25A40 was stronger when only pSS high fatigue patients were analysed versus controls (p = 0.002). One SNP in PKN1 displayed an association in the case-only analysis of pSS high fatigue versus pSS low fatigue (p = 0.005). This candidate gene study in pSS did reveal a trend for associations between genetic variation in candidate genes and fatigue. The results will need to be replicated. More research on genetic associations with fatigue is warranted, and future trials should include larger cohorts and multicentre collaborations with sharing of genetic material to increase the statistical power.
|
|
| 4. |
- Tjensvoll, Anne B, et al.
(författare)
-
Neurofilament light is a biomarker of brain involvement in lupus and primary Sjögren's syndrome.
- 2021
-
Ingår i: Journal of neurology. - : Springer Science and Business Media LLC. - 1432-1459 .- 0340-5354. ; 268
-
Tidskriftsartikel (refereegranskat)abstract
- To test the hypothesis that neurofilament light (NfL) in CSF is a biomarker of CNS involvement in patients with systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (pSS), we measured NfL in CSF from 52 patients with lupus and 54 with pSS and explored associations with clinical, structural, immunological and biochemical abnormalities.In CSF, we measured NfL, anti-P antibodies, protein S100B and TWEAK by ELISA and anti-NR2 antibodies by electrochemiluminescence. Anti-phospholipid antibodies and routine immunological tests were performed in blood. IgG and albumin were measured in CSF and serum for assessment of the blood-brain barrier function (Q-albumin) and intrathecal IgG production (IgG index). Cerebral MRI and neuropsychological testing were performed.A multivariable regression model showed that increasing CSF anti-NR2 antibody levels were associated with increasing NfL levels in patients with SLE (B 1.27, 95% CI 0.88-1.65, p < 0.001). Age contributed significantly in the model (B 0.04, 95% CI 0.03-0.05, p < 0.001). Similar findings were observed in the pSS group. Adjusted for age and sex, no associations were found between NfL levels and any MRI data. In SLE patients, higher NfL concentrations were associated with impairments in psychomotor speed and motor function, and in pSS with motor dysfunction. These associations remained in multivariable regression models.Increased concentration of NfL in CSF is a marker of cerebral involvement in patients with SLE and pSS, is strongly associated with the presence of anti-NR2 antibodies, and correlates with cognitive impairment in several domains.
|
|
