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ABSTRACT. Objective. Smoking contributes to progression of ankylosing spondylitis (AS). Because smoking is also a risk factor for incident rheumatoid arthritis (RA) and psoriatic arthritis, our aim was to test whether smoking habits are associated with incident AS. Methods. Using data from the HUNT health study of the entire adult population of Nord-Trøndelag, Norway, participants in HUNT2 (1995-1997) and HUNT3 (2006 Conclusion. In the HUNT population-based study, incident AS was associated with current smoking and hypertension. If verified in further studies, this suggests that smoking should be discouraged in those at a higher AS risk, e.g., with a family history or carryin

Personal non-commercial use only

ABSTRACT. Objective. Smoking contributes to progression of ankylosing spondylitis (AS). Because smoking is also a risk factor for incident rheumatoid arthritis (RA) and psoriatic arthritis, our aim was to test whether smoking habits are associated with incident AS. Methods. Using data from the HUNT health study of the entire adult population of Nord-Trøndelag, Norway, participants in HUNT2 (1995-1997) and HUNT3 (2006 Conclusion. In the HUNT population-based study, incident AS was associated with current smoking and hypertension. If verified in further studies, this suggests that smoking should be discouraged in those at a higher AS risk, e.g., with a family history or carryin

Exercise training and high-sensitivity cardiac troponin T in patients with heart failure with reduced ejection fraction

Plasma cell disorders (PCDs) are identified in the clinical lab by detecting the monoclonal immunoglobulin (M-protein) which they produce. Traditionally, serum protein electrophoresis methods have been utilized to detect and isotype Mproteins. Increasing demands to detect low-level disease and new therapeutic monoclonal immunoglobulin treatments have stretched the electrophoretic methods to their analytical limits. Newer techniques based on mass spectrometry (MS) are emerging which have improved clinical and analytical performance. MS is gaining traction into clinical laboratories, and has replaced immunofixation electrophoresis (IFE) in routine practice at one institution. The International Myeloma Working Group (IMWG) Mass Spectrometry Committee reviewed the literature in order to summarize current data and to make recommendations regarding the role of mass spectrometric methods in diagnosing and monitoring patients with myeloma and related disorders. Current literature demonstrates that immune-enrichment of immunoglobulins coupled to intact light chain MALDI-TOF MS has clinical characteristics equivalent in performance to IFE with added benefits of detecting additional risk factors for PCDs, differentiating Mprotein from therapeutic antibodies, and is a suitable replacement for IFE for diagnosing and monitoring multiple myeloma and related PCDs. In this paper we discuss the IMWG recommendations for the use of MS in PCDs.publishedVersio

Moderate continuous or high intensity interval exercise in heart failure with reduced ejection fraction : Differences between ischemic and non-ischemic etiology

publishedVersio

Baseline and exercise predictors of VO2peak in systolic heart failure patients : Results from SMARTEX-HF

Author's accepted version (postprint).This is an Accepted Manuscript of an article published by American College of Sports Medicine in Medicine & Science in Sports & Exercise on 04/11/2019.Available online: https://journals.lww.com/acsm-msse/FullText/2020/04000/Baseline_and_Exercise_Predictors_of_V_O2peak_in.5.aspxacceptedVersio

Identification of a regulatory pathway governing TRAF1 via an arthritis-associated non-coding variant

TRAF1/C5 was among the first loci shown to confer risk for inflammatory arthritis in the absence of an associated coding variant, but its genetic mechanism remains undefined. Using Immunochip data from 3,939 patients with juvenile idiopathic arthritis (JIA) and 14,412 control individuals, we identified 132 plausible common non-coding variants, reduced serially by single-nucleotide polymorphism sequencing (SNP-seq), electrophoretic mobility shift, and luciferase studies to the single variant rs7034653 in the third intron of TRAF1. Genetically manipulated experimental cells and primary monocytes from genotyped donors establish that the risk G allele reduces binding of Fos-related antigen 2 (FRA2), encoded by FOSL2, resulting in reduced TRAF1 expression and enhanced tumor necrosis factor (TNF) production. Conditioning on this JIA variant eliminated attributable risk for rheumatoid arthritis, implicating a mechanism shared across the arthritis spectrum. These findings reveal that rs7034653, FRA2, and TRAF1 mediate a pathway through which a non-coding functional variant drives risk of inflammatory arthritis in children and adults

Association of CLEC16A with human common variable immunodeficiency disorder and role in murine B cells

Common variable immunodeficiency disorder (CVID) is the most common symptomatic primary immunodeficiency in adults, characterized by B-cell abnormalities and inadequate antibody response. CVID patients have considerable autoimmune comorbidity and we therefore hypothesized that genetic susceptibility to CVID may overlap with autoimmune disorders. Here, in the largest genetic study performed in CVID to date, we compare 778 CVID cases with 10, 999 controls across 123, 127 single-nucleotide polymorphisms (SNPs) on the Immunochip. We identify the first non-HLA genome-wide significant risk locus at CLEC16A (rs17806056, P = 2.0 x 10(-9)) and confirm the previously reported human leukocyte antigen (HLA) associations on chromosome 6p21 (rs1049225, P = 4.8 x 10(-16)). Clec16a knockdown (KD) mice showed reduced number of B cells and elevated IgM levels compared with controls, suggesting that CLEC16A may be involved in immune regulatory pathways of relevance to CVID. In conclusion, the CLEC16A associations in CVID represent the first robust evidence of non-HLA associations in this immunodeficiency condition

Are Genetic Risk Scores for Arthritis and Cardiovascular Events Predictive in Arthritis Patients on a Population Level? 2019

Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) are chronic inflammatory joint diseases posing a significant burden to patients, their families, and society. They are caused by an interaction between a strong genetic predisposition and environmental factors. RA patients also have increased mortality rates and higher risk of cardiovascular disease, including myocardial infarctions and strokes. The objectives of the project are to test whether risk scores based on published genetic risk variants may predict the risk of RA or AS, if genetic risk scores for RA and for cardiovascular events may predict the risk of mortality or myocardial infarctions in RA patients, and if prediction is improved when adding non-genetic variables. The project uses data from the population-based Nord-Trøndelag Health Study performed in 1995-7 and 2006-8, including questionnaire data on health and lifestyle, data from a clinical examination, and blood samples. Using hospital files, diagnoses were ascertained in 545 RA cases and 190 AS cases. Control data are available from approximately 36,000 individuals. Genotyping of a large number of genetic variants has been done, and linkages have been performed to the National Causes of Death Registry and the Myocardial Infarction Registry of Middle Norway. The main challenge is whether genotypes for all the previously published genetic variations will be available. The findings from the project will increase our understanding of how important the published genetic risk variants are relative to non-genetic risk factors in a general population, how important the contribution from disease-specific risk genes are to the overall risk of cardiovascular events in RA patients, and whether genetic risk factors for cardiovascular events identified in the general population have the same effects in RA patients. Improved predictive risk scores may also permit identification and preventive measures in individuals at high risk of disease development. For further information about "Are Genetic Risk Scores for Arthritis and Cardiovascular Events Predictive in Arthritis Patients on a Population Level? 2019", please contact the principal investigator