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Introduction/Aims: Cytosolic 5′-nucleotidase 1A (cN-1A) autoantibodies have been recognized as myositis-related autoantibodies. However, their correlations with clinical characteristics and other myositis-specific and myositis-associated autoantibodies (MSAs/MAAs) are still unclear. We aimed to establish the prevalence and clinical and laboratory associations of cN-1A autoantibodies in a cohort of patients with connective tissue diseases. Methods: A total of 567 participants (182 idiopathic inflammatory myopathies [IIM], 164 systemic lupus erythematosus [SLE], 121 systemic sclerosis [SSc], and 100 blood donors [BD]) were tested for the presence of cN-1A autoantibodies and other myositis-specific and myositis-associated autoantibodies (MSAs/MAAs). Clinical and laboratory characteristics were compared between anti-cN-1A positive and negative patients with sporadic inclusion body myositis (sIBM) and between anti-cN-1A positive and negative patients with non-IBM IIM. Results: In the sIBM cohort, 30 patients (46.9%) were anti-cN-1A positive vs. 18 (15.2%) in the non-IBM IIM cohort, 17 (10%) were anti-cN-1A positive in the SLE cohort and none in the SSc or the BD cohorts. Anti-cN-1A positivity had an overall sensitivity of 46.9% and a specificity of 93.2% for sIBM. Dysphagia was more frequent in the anti-cN-1A positive vs. negative sIBM patients (p =.04). In the non-IBM IIM group, being anti-cN-1A antibody positive was associated with the diagnosis polymyositis (p =.04) and overlap-myositis (p =.04) and less disease damage evaluated by physician global damage score (p <.001). Discussion: cN-1A autoantibodies were predominantly found in IIM patients and was associated with dysphagia in sIBM patients. Notably, anti-cN-1A appears to identify a distinct phenotype of anti-cN-1A positive non-IBM IIM patients with a milder disease course.

Background: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with increased risk of cardiac dysfunction. The pathophysiological mechanisms are poorly understood, and prognostic markers are warranted. Purpose: We aimed to identify SLE-characteristics associated with measures of cardiac size and function during a five-year follow-up. Methods: We included 108 patients with SLE: 90% females, mean age 46 ± 13 years, median disease duration 14 (range 7–21) years. We performed blood sampling for potential biomarkers as well as a standard echocardiography at baseline and at a 5-year follow-up. To investigate associations with baseline and prospective 5-year changes in echocardiographic parameters, we performed multivariate regression analyses of SLE-related baseline variables (clinical disease activity, lupus nephritis, chronic kidney disease, anti-cardiolipin and/or anti-beta-2 glycoprotein I antibodies, and lupus anticoagulant (LAC)) and adjusted for traditional risk factors. Results: During follow-up, diastolic function regressed in two out of five echocardiographic measures (E/A ratio 1.4 ± 0.5 vs. 1.3 ± 0.5, p = 0.002; tricuspid regurgitation peak velocity 2.0 ± 0.6 vs. 2.2 ± 0.4 mmHg, p < 0.001). Left ventricular (LV) end-diastolic volume index increased (43.7 ± 13.9 vs. 52.5 ± 15.7 mL/m2, p < 0.001). Left and right ventricular systolic function remained stationary. LAC was associated with inferior diastolic function: lower E/A ratio (p = 0.04) and higher E/e’ ratio at baseline (p = 0.04) and increased left ventricular atrial volume index during follow-up (p = 0.01). LAC was further associated with LV dilatation during follow-up (p = 0.01). Conclusion: Presence of LAC was associated with measures of diastolic function as well as progressive LV dilatation during the 5-year follow-up. Thus, LAC might be a predictor of cardiac dysfunction in SLE patients. LAC is known to have implications for the microvascular circulation, but the cl

Objective: . To assess the role of LN as a risk factor for myocardial infarction (MI), stroke and cardiovascular mortality (CVM) in patients with SLE.Methods: . The study was conducted using individual-level data from multiple nationwide registers. We identified a cohort of patients diagnosed with SLE and further determined if they had a diagnosis of LN during 1995-2011. Each SLE patient was matched with five population controls. Hazard ratios (HRs) were calculated to measure the risk of MI, stroke and CVM in SLE patients relative to population controls and in SLE patients with relative to without LN.Results: . We identified 1644 SLE patients with incident SLE; 233 of these patients had a diagnosis of incident LN during follow-up. The number of events in the SLE cohort was: 42 (MI), 74 (stroke) and 56 (CVM). For MI, the HR was 2.2 (95% CI: 1.4, 3.4) in SLE without LN and 18.3 (95% CI: 5.1, 65) in SLE with LN. The HR for LN was 8.5 (95% CI: 2.2, 33; P = 0.002). For stroke, HRs were 2.1 (95% CI: 1.5, 2.9) and 4.1 (95% CI: 1.9, 8.7) in SLE without and with LN, respectively, and we found no significant association with LN (P = 0.115). For CVM, the respective HRs were 1.6 (95% CI: 1.1, 2.4) and 7.8 (95% CI: 3.0, 20). The corresponding HR for LN was 4.9 (95% CI: 1.8, 13.7; P = 0.002).Conclusion: . The risk of MI and CVM, but not of stroke, is significantly higher in SLE patients with LN than SLE patients without LN.

Objective. To determine the incidence of systemic lupus erythematosus (SLE) and SLE with concomitant or subsequent lupus nephritis (LN) in Denmark during 1995.2011, using data from the Danish National Patient Registry (NPR). Methods. To assess the incidence of SLE, we identified all persons aged . 18 years in the NPR with at least 1 International Classification of Diseases, 10th ed (ICD-10) code of SLE and at least 365 days of followup under this diagnosis. Identification of LN cases was based on fulfillment of these criteria and . 1 registration under an ICD-10 code of nephritis concomitantly with or after first SLE registration. Results. The overall annual incidence rate per 100,000 for SLE was 2.35 (95% CI 2.24.2.49); 0.69 (95% CI 0.60.0.78) for men and 3.96 (95% CI 3.75.4.17) for women. For LN, the mean annual incidence rate per 100,000 was estimated to be 0.45 (95% CI 0.38.0.53); 0.20 (95% CI 0.13.0.28) for men and 0.69 (95% CI 0.57.0.83) for women. The differences in SLE incidence rates between sexes decreased by age, and the incidence did not differ between men and women after the age of 60 years for LN. The estimated incidences showed no trends by calendar time. Estimated overall point prevalence (December 31, 2011) per 100,000 was 45.2 (95% CI 43.3.47.4) and 6.4 (95% CI 5.7.7.2) for SLE and LN, respectively. Conclusion. Our Danish population-based data showed a stable incidence of SLE and LN. As expected, we found higher incidence rates among women than among men, particularly in younger persons.

This study aimed to demonstrate possible associations between genetic polymorphisms in Toll-like receptor 3, interferon induced with helicase C domain 1 (IFIH1) and DEAD (Asp-Glu-Ala-Asp) box polypeptide 58 and systemic lupus erythematosus (SLE), including the phenotypes lupus nephritis and malar rash, as well as the presence of autoantibodies against nucleic acid-containing complexes. Genotyping was carried out in two Danish cohorts [Copenhagen (CPH) and Odense (ODE)] totaling 344 patients and was compared with 641 previously genotyped healthy controls. In the ODE cohort, the patients were only genotyped for the rs1990760 polymorphism of IFIH1. Single nucleotide polymorphisms (SNPs) were determined by a multiplex bead-based assay (CPH cohort) or real-time PCR (ODE cohort). Associations were investigated using the Cochran-Armitage trend test. The odds ratio (OR) for minor allele homozygotes versus major allele homozygotes suggested a protective effect of the IFIH1 rs1990760 SNP for SLE in the ODE cohort [OR 0.52, 95 % confidence intervals (95 % CI) 0.31-0.88, Pcorr. = 0.05] but not in the CPH cohort, although the OR suggested a trend in the same direction, and when combining the two patient cohorts, ORs were 0.57, 95 % CI 0.37-0.88. None of the other investigated polymorphisms showed any association with SLE. Regarding phenotypes, we found a statistically significant association between rs1990760 and malar rash in the CPH cohort, with ORs suggesting a protective effect (OR 0.28, 95 % CI 0.13-0.62 for heterozygotes and OR 0.11, 95 % CI 0.03-0.41 for homozygotes, Pcorr. = 0.0001). There were no significant associations between rs1990760 and presence of anti-dsDNA, anti-U1RNP, or anti-Smith antibodies. Our study supports previous findings of an association between the rs1990760 polymorphism of IFIH1 and SLE and indicates that this SNP may also be associated with malar rash in SLE patients although this finding needs confirmation.

Several studies indicate a role for toll-like receptors (TLRs) in the pathogenesis of systemic lupus erythematosus (SLE). We aimed to investigate the risk of SLE and typical clinical and serological manifestations of SLE potentially conferred by selected single nucleotide polymorphisms (SNPs) of genes encoding TLR7, TLR8, and TLR9. Using a multiplexed bead-based assay, we analyzed eight SNPs in a cohort of 142 Danish SLE patients and a gender-matched control cohort comprising 443 individuals. Our results showed an association between the rs3853839 polymorphism of TLR7 and SLE (G vs. C, P = 0.008, OR 1.60, 95 % CI 1.12-2.27 in females; P = 0.02, OR 4.50, 95 % CI 1.18-16.7 in males) confirming recent findings in other populations. Additionally, an association between the rs3764879 polymorphism of TLR8 and SLE (G vs. C, P < 0.05, OR 1.36, 95 % CI 0.99-1.86 in females; P = 0.06, OR 4.00, 95 % CI 0.90-17.3 in males) was found. None of the other investigated SNPs were associated with SLE but several SNPs were associated with clinical and serological manifestations. In summary, a previously shown association between the rs3853839 SNP of TLR7 and SLE in Asian patients was also found in Danish patients. Together with the association of several other SNPs of TLR8 and TLR9 with various clinical and serological manifestations of SLE these findings corroborate the pathogenic significance of TLRs in SLE.

Kjeld Hermansen, Lene Sundahl Mortensen, Marie-Louise HermansenDepartment of Endocrinology and Metabolism C, Aarhus University Hospital, DK-8000 Aarhus, DenmarkAbstract: Patients with type 2 diabetes mellitus (T2DM) have an increased risk of cardiovascular disease (CVD). Unfortunately, several potential barriers exist for CVD risk management in diabetes, including the need for significant lifestyle changes, potential problems with hypoglycemia, weight gain, injection tolerability, treatment complexity with current diabetes therapies and other, unmodifiable factors. Improving glycemic control may impact CVD risk. Treatment of T2DM usually starts with lifestyle changes such as diet and exercise. When these become insufficient, pharmacotherapy is required. Various oral antidiabetic drugs (OADs) are available that reduce hyperglycemia. The first line of therapy is usually metformin, since it does not increase weight and seems to have a beneficial effect on CVD mortality and risk factors. As T2DM progresses, insulin treatment becomes necessary for the majority of patients. The last few years have seen the development of long-acting, rapid-acting, and premixed insulin analog formulations. The treat-to-target algorithms of recent studies combining OADs plus insulin analogs have demonstrated that patients can reach glycemic treatment targets with low risk of hypoglycemia, greater convenience, and – with some analogs – limited weight gain vs conventional insulins. These factors may possibly have a positive influence on CVD risk. Future studies will hopefully elucidate the benefits of this approach.Keywords: diabetes mellitus, type 2 diabetes, cardiovascular disease, hyperglycemia, insulin, oral antidiabetic drugs