Labordiagnostik bei systemischen Autoimmunerkrankungen

The detection of autoantibodies is well established in daily clinical practice for evaluation of systemic autoimmune diseases like rheumatoid arthritis (RA), connective tissue diseases and vasculitides. Rheumatoid factor (RF) or the anti-citrullinated protein antibody (ACPA) is only observed in approximately 80% of patients suffering from rheumatoid arthritis. Anti-CarP autoantibodies might serve as a novel marker, filling this gap. The detection of ANA (anti-nuclear antibody) facilitates the diagnosis of connective tissue diseases. Elevated levels of anti-centromer antibodies, anti-topoisomerase I [anti-Scl-70] antibodies and the anti-RNA polymerase III antibodies, which belong to the group of ANA, are frequently present in the serum of patients suffering from systemic sclerosis and are therefore incorporated into the new classification criteria. To establish the diagnosis of an antiphospholipid syndrome, the detection of the lupus anticoagulant and the aCL-/anti-beta 2GPI-antibodies of IgG, IgM and IgA isotypes plays a pivotal role. The anti-neutrophil cytoplasmic antibodies (ANCAs) are associated with vasculitides of small vessels. Screening with immunofluorescence testing (IFT) is established as the first step followed by additional immunoassays specific for proteinase 3 (PR3) and myeloperoxidase (MPO) autoantibodies. Novel bedside test procedures for these antibodies allow an early diagnosis in critically ill patients. New biomarkers for polymyalgia rheumatic and for spondyloarthritides are also described, but their clinical relevance remains uncertain and necessitates further studies

Targeting activated synovial fibroblasts in rheumatoid arthritis by peficitinib

Background: Synovial fibroblasts (SF) play a major role in the pathogenesis of rheumatoid arthritis (RA) and develop an aggressive phenotype destroying cartilage and bone, thus termed RASF. JAK inhibitors have shown to be an efficient therapeutic option in RA treatment, but less is known about the effect of JAK inhibitors on activated RASF. The aim of the study was to examine the effects of JAK inhibitors on activated RASF. Methods: Synovium of RA patients was obtained during knee replacement surgeries. Synoviocytes were isolated and pretreated with JAK inhibitors. Pro-inflammatory cytokines and matrix degrading proteinases were measured by ELISA in supernatant after stimulation with oncostatin M or IL-1β. The proliferation of RASF was measured by BrdU incorporation. Cell culture inserts were used to evaluate cell migration. For adhesion assays, RASF were seeded in culture plates. Then, plates were extensively shaken and adherent RASF quantified. Cell viability, cytotoxicity and apoptosis were measured using the ApoTox-Glo™ Triplex and the CellTox™ Green Cytotoxicity Assay. Results: Tofacitinib and baricitinib decreased the IL-6 release of RASF stimulated with oncostatin M. JAK inhibition attenuated the IL-6 release of IL-1β activated and with soluble IL-6 receptor treated RASF. In contrast, only peficitinib and filgotinib decreased the IL-6 release of RASF activated with IL-1β. Peficitinib decreased also the MMP-3, CXCL8, and CXCL1 release at 5 μM. Moreover, peficitinib was the only JAK inhibitor suppressing proliferation of activated RASF at 1 μM. Peficitinib further decreased the migration of RASF without being cytotoxic or pro-apoptotic and without altering cell adhesion. Conclusions: JAK inhibitors effectively suppress the inflammatory response induced by oncostatin M and by transsignaling of IL-6 in RASF. Only peficitinib modulated the IL-1β-induced response of RASF and their proliferation in vitro at concentrations close to reported Cmax values of well tolerated doses in vivo. In contrast to filgotinib, peficitinib also highly suppressed RASF migration showing the potential of peficitinib to target RASF

Adipokine expression in systemic sclerosis lung and gastrointestinal organ involvement

OBJECTIVES The immunomodulatory properties of adipokines have previously been reported in autoimmune disorders. Less is known about the role of adipokines in systemic sclerosis (SSc). Lung and gastrointestinal tract are frequently involved in SSc; therefore, these organs were analyzed for adipokine expression as well as pulmonary samples of patients suffering from idiopathic pulmonary fibrosis (IPF) as comparison. METHODS Gastric samples (antrum, corpus) of SSc were analyzed immunohistochemically for adiponectin, resistin and visfatin compared with non-SSc related gastritis. Inflammatory cells were quantified in gastric samples and correlated with adipokine expression. Lung samples of SSc, IPF and healthy controls were also analyzed. Protein levels of lung tissue lysates and bronchoalveolar lavages (BAL) in minor fibrotic stages were measured by ELISA. RESULTS Lung sections of donor parenchyma showed significantly stronger adiponectin signals as IPF and SSc (donor vs. IPF: p < 0.0001). In SSc and IPF, resistin and visfatin were increased within immune cell infiltrates, but overall no difference in expression for resistin or visfatin compared to controls was observed. In BAL and lung protein lysates of early stages of fibrosis, adiponectin and visfatin were not reduced in IPF and SSc compared to controls. In gastric samples collected by standard endoscopic gastric biopsy, adiponectin was also significantly reduced in SSc- compared to non-SSc gastritis (p = 0.049) while resistin and visfatin were comparable although deeper fibrotic layers were not included in the respective samples. Adiponectin-positive tissues showed higher amounts of CD4 but not CD8 T cells. Controls showed no correlation between CD4 T cells and resistin, whereas SSc showed significantly more CD4 T cells in resistin-negative tissues. CONCLUSION Adipokines are expressed in gastric and lung samples of patients with SSc and in lung samples affected by IPF. Prominently, adiponectin levels were reduced in fibrotic SSc gastritic tissue as well as in IPF and SSc lung tissue. Consequently, adiponectin expression seems to be associated with fibrotic progression in the context of SSc and IPF

The Hawthorne effect on adherence to hand hygiene in patient care: a systematic review

Background: Numerous studies demonstrate that the Hawthorne effect (behaviour change caused by awareness of being observed) increases health workers’ hand hygiene adherence but it is not clear if they are methodologically robust, magnitude of the effect, how long it persists or whether it is the same across clinical settings. Objective: Determine rigour of the methods used to assess the Hawthorne effect on hand hygiene, effect size estimation, variations between clinical settings and persistence. Methods: Systematic literature review with meta-analysis. Results: Nine studies met the criteria for the review. Methodological quality was poor. Data pooling was possible across six studies. The Hawthorne effect ranged from 4.2% to 65.3% with a median of 35.6%. It was 4.2% in one study conducted in intensive care and 16.4% in transplant units. It was most marked when data were collected across an entire hospital and in a group of general hospitals. Differences between wards in the same hospital were apparent. In the two studies where duration was estimated, the Hawthorne effect appeared transient. Conclusions: Despite methodological shortcomings the review indicates clear evidence of a Hawthorne effect on general wards. There is some evidence that it may vary according to clinical specialty and across different wards within the same organisation. The review identifies a need for standardised methodologies to measure the Hawthorne effect in hand hygiene to overcome the dilemma of reporting the potentially inflated rates of adherence obtained through overt audit. Occasional covert audit could give a better estimation of ‘real’ hand hygiene adherence but its acceptability and feasibility to health workers need to be explored

Value differences as determinants of importers' perceptions of exporters' unethical behavior: The impact on relationship quality and performance

The article focuses on the value drivers of the unethical marketing behavior of exporters, as seen from the perspective of their importers, and how this in turn affects the quality of their working relationship and performance. Based on a sample of 189 Cypriot importers, the study revealed that similarities in national, corporate, and personal values between importers and their foreign suppliers are negatively related to unethical marketing practices of the latter as perceived by the former, and vice versa. Perceived export marketing unethicality, in turn, negatively influences the exporter-importer relationship quality (as expressed in terms of cooperation, communication, trust, and commitment), which subsequently has harmful effects on the performance of the relationship. In addition, the existence of a high similarity in both value strength and ethical codes between importers and their export suppliers was found to positively affect the quality of the working relationship. Finally, the association of both corporate and personal values similarity with perceived export marketing unethicality was found to be moderated by network ties, although this was not evident in the case of national values similarity. The findings of the study have important implications for import managers in terms of properly selecting and handling relationships with their foreign suppliers