BackgroundCalprotectin (S100A8/A9 or MRP8/14) and S100A12 (leukocyte-derived proteins), interleukin 6 (IL-6) and vascular endothelial growth factor (VEGF) are markers of inflammation and angiogenesis. Ultrasound (US) is sensitive for detection of greyscale synovitis and power Doppler (PD) vascularization. The objective of the present study was to explore the associations between calprotectin, S100A12, IL-6, VEGF, erythrocyte sedimentation rate, C-reactive protein and a comprehensive US assessment in patients with rheumatoid arthritis (RA) starting biologic disease-modifying anti-rheumatic drug (bDMARD) treatment.MethodsA total of 141 patients with RA were assessed by US, clinical examination and biomarker levels at baseline and at 1, 2, 3, 6 and 12 months after initiation of bDMARDs. US assessment of 36 joints and 4 tendon sheaths were scored semi-quantitatively (0–3 scale). European League Against Rheumatism (EULAR) response was calculated. Statistical assessments performed to explore the associations between biomarkers and US sum scores included Spearman’s rank correlation analysis as well as linear and linear mixed model regression analyses.ResultsCalprotectin showed the overall strongest correlations with both US sum scores (r s = 0.25–0.62) and swollen joint counts (of 32) (r s = 0.24–0.47) (p < 0.05 at all examinations). An association with US sum scores remained after we adjusted for age, sex, disease duration and all the other markers in a regression analysis at baseline. Decreased calprotectin at the first month was predictive of both EULAR response (p ≤ 0.001) and decreased sum PD scores at 3, 6 and 12 months (p ≤ 0.05).ConclusionsCalprotectin had the highest association with US synovitis and predicted treatment response. It may thus be considered as a marker for evaluating inflammation and responsiveness in patients with RA on bDMARD treatment.Trial registrationAustralian New Zealand Clinical Trials Registry (ANZCTR) identifier: ACTRN12610000284066. Registered on 8 April 2010 (retrospectively registered).Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-016-1201-0) contains supplementary material, which is available to authorized users.

ObjectivesHerein, we investigate the presence and prognostic value of autoantibodies against carbamylated proteins (anti-CarP) in the serum of patients with primary Sjögren's syndrome (pSS).Patients and methodsSerum levels of anti-CarP antibodies were measured in Norwegian patients with pSS (n=78) and corresponding controls (n=74) using ELISA and analysed in relation with exocrine gland function, degree of salivary gland inflammation, signs of ectopic germinal centre (GC) formation and immunological markers. For univariate comparisons, the Mann–Whitney U test and χ2 or Fisher's exact tests were used. Correlations were assessed with Spearman's rank testing. Multivariate regression analyses were used to assess the effect of anti-CarP positivity on clinical manifestations.ResultsOf the patients with pSS, 27% were positive for anti-CarP IgG antibodies. Levels of anti-CarP correlated positively with total IgG, IgM, rheumatoid factor and β2-microglobulin. Importantly, after adjusting for confounding factors, patients positive for anti-CarP had significantly higher focus score. Furthermore, positive anti-CarP status coincided with 9.2-fold higher odds of having developed GC-like structures in the minor salivary glands. As a patient group considered having worse disease outcome, individuals with ectopic GC-like structures also presented with significantly higher levels of anti-CarP antibodies.ConclusionsPresence of anti-CarP in patients with pSS is strongly associated with increased focal lymphocytic infiltration, formation of ectopic GC-like structures in minor salivary glands, and diminished salivary gland function. Even taking into consideration our relatively small cohort we believe that anti-CarP antibodies offer new possibilities for identifying patients with more active disease and at risk of developing additional comorbidity.

BackgroundReform of health services has given primary care facilities increased responsibility for patients with serious mental disorders (SMD). There has also been a growing awareness of the high somatic morbidity among SMD patients, an obvious challenge for general practitioners (GPs). The aim of this study was to assess the utilisation of GP services by patients with schizophrenia.MethodsThe Norwegian list patient system is based on fee-for-service (FFS). For each contact, the GPs send a claim to National Health Insurance detailing the diagnosis, the type of contact, procedures performed, and the personal identifier of the patient. In this study complete GP claims data from 2009 for schizophrenia patients aged 25–60 years were used to assess their utilisation of GP services. Regression models were used to measure the association between patient, GP and practice characteristics, with FFS per patient used as a measure of service utilisation. Data on patients with diabetes (DM) and population means were used for comparison.ResultsThe mean annual consultation rate was 5.0 and mean FFS was 2,807 Norwegian Kroner (NOK) for patients diagnosed with schizophrenia. Only 17% had no GP consultation, 26.2% had one or two, 25.3% had three to five, and 16.1% more than five consultations. GPs participated in multidisciplinary meetings for 25.7% of these patients. In schizophrenia patients, co-morbid DM increased the FFS by NOK 1400, obstructive lung disease by NOK 1699, and cardiovascular disease by NOK 863. The FFS for schizophrenia patients who belonged to a GP practice with a high proportion of mental health-related consultations increased by NOK 115 per percent point increase in proportion of consultations. Patients with schizophrenia living in municipalities with < 10,000 inhabitants had a mean increase in FFS of NOK 1048 compared with patients living in municipalities with > 50,000 inhabitants. Diagnostic tests were equally or more frequent used among patients with schizophrenia and comorbid somatic conditions than among similar patients without a SMD.ConclusionThis study showed that most patients diagnosed with schizophrenia had regular contact with their GP, providing opportunities for the GP to care for both mental and somatic health problems.

An accurate dissection of peripheral blood enumeration is lacking in primary Sjögren's syndrome (pSS). The purpose of this study was to quantify different leucocyte populations in peripheral blood of patients with pSS. Numbers of specific leucocyte subsets were determined in 86 pSS patients and 74 healthy donors quantifying 21 distinct subtypes by flow cytometry. Subgroups of pSS patients were stratified based on presence of extraglandular manifestations (EGMs) and SSA/SSB autoantibodies. Overall, pSS patients manifested decreased lymphocyte subpopulations compared to healthy donors. Such decreases were more pronounced in SSA/SSB positive patients and patients with EGM. Granulocyte and monocyte subpopulations were increased in pSS patients compared to healthy donors, with the greatest increases in SSA/SSB positive patients. Unsupervised hierarchal clustering based on cell quantities was used to further subgroup the pSS patients into four clusters. One of the clusters characterized by higher concentrations of NKT cells, CD56hi NK cells, CD20 CD38 B cells and CD8 CD38 T cells was associated with weaker clinical symptoms than the other clusters, possibly marking a milder disease phenotype. In conclusion, our analyses indicate significant alterations in the cellular profiles of peripheral blood leucocytes in patients with pSS and may help to stratify the patients according to disease severity.

Chronic graft versus host disease (cGVHD) is the most common long-term complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). During the last decade, the interest of micro RNAs (miRNAs) in the pathophysiological process of cGVHD has increased. The objectives of this study were to investigate a wide range of serum miRNAs in allografted patients and identify associations between miRNAs and cGVHD. The study included 79 allotransplanted adults, where serum samples were obtained one year after the allo-HSCT, and miRNA profiling analysis in serum was performed. 50 of the 79 patients (63%) had signs of cGVHD at the one-year post-allo-HSCT control. miRNA-sequencing analysis revealed 1380 different miRNAs detected for at least one patient, while 233 miRNAs (17%) were detected in more than 70 patients. We identified ten miRNAs that differed significantly between patients with and without cGVHD (p &lt;0.005, false discovery rate (FDR) &lt;0.1), and all or these miRNAs were detected for &gt;75 of the patients. Furthermore, five distinct miRNAs; miR-365-3p, miR-148-3p, miR-122-5p, miR-378-3p, and miR-192-5p, were found to be particularly associated with cGVHD in our analysis and validated by receiver operating characteristics (ROC) analysis. Based on only three miRNAs, miR-365-3p, miR-148-3p, and miR-378-3p, we developed a miRNA signature which by bioinformatic approaches and linear regression model utterly improved our potential diagnostic biomarker model for cGVHD. We conclude that miRNAs are differently expressed among patients with and without cGVHD, although further and larger studies are needed to validate our present findings.