Myeloperoxidase was isolated from leucocytes obtained from the blood of patients suffering from chronic granulocytic leukaemia. The enzyme was purified 850 fold and was homogeneous in ultracentrifuge and free boundary electrophoresis. The molecular weight of the enzyme was found to be about 160,000. The enzyme forms a spectrally characteristic complex with hydrogen peroxide with absorption maximum at 458 mμ. The spectrum of the native enzyme has absorption maxima at 430 and 570 mμ. The reduced enzyme is characterized by a spectrum with absorption maxima at 472 and 637 mμ. The investigated myeloperoxidase catalysed oxidation of amino acids by hydrogen peroxide. Products of the oxidation of amino acids were ammonia, carbon dioxide, and an aldehyde corresponding to the oxidized amino acid. The observed reaction of deamination and decarboxylation is activated by chloride ions. In the presence of the chloride ions the optimum of the reaction is shifted toward the higher pH values. The velocity of the reaction was found to be dependent on the concentration of the amino acid studied. Km values for various amino acids increased in the range 3.4 × 10−4 to 10−3 M in proportion to rising hydrophobic properties of the substrates. Taurine was found to be a competitive inhibitor in the examined reaction, and Ki values were in the range of 2 to 3 × 10−4 M, for different amino acids.

Since publication of the ACR criteria for vasculitis, the sensitivity for each type of vasculitis, except GCA, has diminished, although the specificities have remained high, highlighting the need for updated classification criteria.

The objective of our study was to evaluate the T-helper (Th) and regulatory T (Treg) cell profile in ANCA-positive granulomatosis with polyangiitis (GPA) and its relation to disease activity. In a prospective study, we studied two groups of GPA patients: (i) disease flare (active-GPA, BVAS>6, n = 19), (ii) sustained remission (≥ 1-year prior enrollment, inactive-GPA, BVAS = 0, n = 18). 24 age-sex matched healthy subjects served as controls. Active-GPA patients were followed for 6 months and reevaluated during remission (early remission; n = 13). We analyzed subsets of Th-cells (flow cytometry), production of signature cytokines by in vitro stimulated lymphocytes, and broad spectrum of serum cytokines (Luminex). In all GPA patients we observed expansion of effector Th17 cells, and increased production of IL-17A by in vitro stimulated T cells, as compared to controls. Disease flare was characterized by marked reduction in Treg cells, whereas in sustained remission we showed expansion of both Treg and Th2 subset. Finally, analyzing the cytokine profile, we identified CCL23 and LIGHT, as potential biomarkers of active disease. We conclude that in GPA, expansion of Treg and Th2 lymphocytes in parallel to increased Th17 response is a characteristic feature of sustained remission. In contrast, Treg cells are markedly decreased in disease flare.

No abstract

The 2016 European Vasculitis Society (EUVAS) meeting, held in Leiden, the Netherlands, was centered around phenotypic subtyping in antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV). There were parallel meetings of the EUVAS petals, which here report on disease assessment; database; and long-term follow-up, registries, genetics, histology, biomarker studies, and clinical trials. Studies currently conducted will improve our ability to discriminate between different forms of vasculitis. In a project that involves the 10-year follow-up of AAV patients, we are working on retrieving data on patient and renal survival, relapse rate, the cumulative incidence of malignancies, and comorbidities. Across Europe, several vasculitis registries were developed covering over 10,000 registered patients. In the near future, these registries will facilitate clinical research in AAV on a scale hitherto unknown. Current studies on the genetic background of AAV will explore the potential prognostic significance of genetic markers and further refine genetic associations with distinct disease subsets. The histopathological classification of ANCA-associated glomerulonephritis is currently evaluated in light of data coming out of a large international validation study. In our continuous search for biomarkers to predict clinical outcome, promising new markers are important subjects of current research. Over the last 2 decades, a host of clinical trials have provided evidence for refinement of therapeutic regimens. We give an overview of clinical trials currently under development, and consider refractory vasculitis in detail. The goal of EUVAS is to stimulate ongoing research in clinical, serological, and histological management and techniques for patients with systemic vasculitis, with an outlook on the applicability for clinical trials.