The aim of this study was to investigate pentraxin-3 (PTX3) as a potential biomarker of inflammatory activity in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) ...at baseline and 6 month follow-up in a longitudinal cohort.
Plasma PTX3 levels were measured in 79 newly diagnosed or relapsing AAV patients at baseline and 6 month follow-up, and in 23 healthy controls. Urinary PTX3 levels were measured in 34 of the patients. C-reactive protein (CRP), creatinine, and albuminuria were measured and the cumulative glucocorticoid dose at inclusion was calculated. The Birmingham Vasculitis Activity Score (BVAS) was assessed at baseline and follow-up.
Plasma PTX3 levels were significantly higher at baseline than at 6 months (2.85 vs 1.23 ng/mL, p < 0.001). Plasma and urinary PTX3 levels correlated with BVAS at baseline (ρ = 0.45, p < 0.001, and ρ = 0.49, p = 0.008, respectively). A significant correlation between both plasma and urinary PTX3 levels and estimated glomerular filtration rate and albuminuria was found. However, there was no correlation between plasma and urinary PTX3 levels. At baseline, plasma and urinary PTX3 levels were significantly higher in patients with kidney involvement. PTX3 levels did not correlate with CRP, nor was there a correlation between CRP levels and BVAS at baseline.
Plasma and urinary PTX3 seem to reflect disease activity in AAV better than the commonly used CRP. PTX3 may have a potential role as a biomarker in monitoring disease activity in AAV patients, particularly in patients with kidney involvement.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
To investigate presence of circulating myeloperoxidase-positive microparticles (MPO
+
MPs) in relation to disease activity in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated ...vasculitis (AAV). Forty-six patients with AAV and 23 age- and sex-matched healthy controls were included. Vasculitis disease activity was assessed using the Birmingham Vasculitis Activity Score (BVAS). MPs were analyzed in citrate plasma by flow cytometry and phenotyped based on MPO expression and co-expression of pentraxin-3 (PTX3), high mobility group box 1 protein (HMGB1), and tumor necrosis factor-like weak inducer of apoptosis (TWEAK). Serum levels of PTX3, sTWEAK, and HMGB1 were also determined. Twenty-three patients had active vasculitis (BVAS ≥ 1). Concentrations of MPO
+
MPs expressing PTX3, HMGB1, and TWEAK were significantly higher in patients compared to healthy controls (
p
< 0.001,
p
< 0.01,
p
< 0.001, respectively), while concentrations of PTX3
+
and HMGB1
+
MPO
+
MPs were significantly higher in active AAV compared to patients in remission. MPO
+
MPs expressing either PTX3 or HMGB1 were associated with BVAS (
r
= 0.5,
p
< 0.001;
r
= 0.3,
p
= 0.04, respectively). Significantly higher serum PTX3 levels were found in active- than in inactive AAV (
p
< 0.001), correlating strongly with BVAS (
r
= 0.7,
p
< 0.001). Serum levels of sTWEAK and HMGB1 did not differ between patients and controls. Concentration of MPO
+
MPs is increased in plasma from AAV patients compared to healthy individuals. PTX3 in serum as well as PTX3 and HMGB1 expressed on MPO
+
MPs were associated with disease activity in the investigated patients.
Key messages
Myeloperoxidase-positive microparticles (MPO
+
MPs) are increased in plasma from patients with ANCA-associated vasculitis.
Concentrations of MPO
+
MPs expressing PTX3, HMGB1, and TWEAK were significantly higher in patients compared to healthy controls.
MPO
+
MPs expressing PTX3 and HMGB1 are associated with disease activity in ANCA-associated vasculitis.
The antipsychotic clozapine is uniquely effective in the management of schizophrenia; however, its use is limited by its potential to induce agranulocytosis. The causes of this, and of its precursor ...neutropenia, are largely unknown, although genetic factors have an important role. We sought risk alleles for clozapine-associated neutropenia in a sample of 66 cases and 5583 clozapine-treated controls, through a genome-wide association study (GWAS), imputed human leukocyte antigen (HLA) alleles, exome array and copy-number variation (CNV) analyses. We then combined associated variants in a meta-analysis with data from the Clozapine-Induced Agranulocytosis Consortium (up to 163 cases and 7970 controls). In the largest combined sample to date, we identified a novel association with rs149104283 (odds ratio (OR)=4.32, P=1.79 × 10
), intronic to transcripts of SLCO1B3 and SLCO1B7, members of a family of hepatic transporter genes previously implicated in adverse drug reactions including simvastatin-induced myopathy and docetaxel-induced neutropenia. Exome array analysis identified gene-wide associations of uncommon non-synonymous variants within UBAP2 and STARD9. We additionally provide independent replication of a previously identified variant in HLA-DQB1 (OR=15.6, P=0.015, positive predictive value=35.1%). These results implicate biological pathways through which clozapine may act to cause this serious adverse effect.
Correction to: Molecular Psychiatry advance online publication, 12 July 2016; doi:10.1038/mp.2016.97 The ninth author’s name was presented incorrectly. It should have been listed as LF Jarskog.
Objectives – Polymorphisms in the prion protein gene in humans influence susceptibility to, and phenotype of, prion diseases. Methionine–methionine (MM) homozygosity at codon 129 is a risk factor ...for sporadic Creutzfeldt–Jakob disease (CJD). Polymorphism at codon 117 and changes in the octapeptide repeat region have been associated with genetic CJD. Knowledge of genetic background in normal populations may contribute to better understanding of prion diseases.
Materials and methods – Polymorphism at codon 129, codon 117 and deletions of octapetide repeats were studied in 208 healthy blood donors of both genders and of different age.
Results – Polymorphism at codon 129 was: MM 46.6%, methionine–valine 44.7%, valine–valine 8.7%. Polymorphism at codon 117 was observed in 4.8%. Deletions of octapeptide repeats were not detected. There were no gender or age differences in the distribution of codon 129 polymorphism. The frequency of codon 129 polymorphisms was, with one exception, not significantly different from that observed elsewhere in Europe.
Spread of SARS-CoV-2 in the Icelandic Population Gudbjartsson, Daniel F; Helgason, Agnar; Jonsson, Hakon ...
The New England journal of medicine,
06/2020, Letnik:
382, Številka:
24
Journal Article
Recenzirano
Odprti dostop
Despite timely implementation of testing for SARS-CoV-2 virus, a contact-tracing scheme, and social-distancing measures, infection has spread in Iceland. However, there was no detected increase in ...the proportion of infected persons between March 13 and April 4, 2020.
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