Kazuo Suzuki

Presence of anti-phosphatidylserine-prothrombin complex antibodies and anti-moesin antibodies in patients with polyarteritis nodosa

We measured both serum anti‐phosphatidylserine–prothrombin complex (anti‐PSPT) antibodies and anti‐moesin antibodies, as well as various cytokines (interleukin [IL]‐2, IL‐4, IL‐5, IL‐10, IL‐13, IL‐17, granulocyte macrophage colony‐stimulating factor, γ‐interferon, tumor necrosis factor‐α) levels in polyarteritis nodosa (PAN) patients with cutaneous manifestations. All patients showed the presence of a histological necrotizing vasculitis in the skin specimen. They were treated with i.v. cyclophosphamide pulse therapy (IV‐CY) and prednisolone therapy or steroid pulse therapy. The immunological assessments were performed on sera collected prior to and after treatment with IV‐CY or steroid pulse therapy. We found a significant positive correlation between serum anti‐moesin antibodies and both clinical Birmingham Vasculitis Activity Scores and Vasculitis Damage Index. Anti‐PSPT antibody and IL‐2 levels after treatment in PAN patients were significantly lower than before treatment. In contrast, anti‐moesin antibody levels were higher following IV‐CY or steroid pulse therapy compared with the pretreatment levels. In the treatment‐resistant PAN patients (n = 8), anti‐PSPT antibody levels after treatment were significantly lower than before treatment. In contrast, anti‐moesin antibody levels after treatment in the patients were significantly higher compared with the pretreatment levels. Immunohistochemical staining revealed moesin overexpression in mainly fibrinoid necrosis of the affected arteries in the PAN patients. We suggest that measurement of serum anti‐PSPT antibody levels could serve as a marker for PAN and aid in earlier diagnosis of PAN. We also propose that elevated serum anti‐moesin antibodies could play some role of the exacerbation in patients with PAN.

Correlation of interleukin‐6 and monocyte chemotactic protein‐1 concentrations with crescent formation and myeloperoxidase‐specific anti‐neutrophil cytoplasmic antibody titer in SCG/Kj mice by treatment with anti‐interleukin‐6 receptor antibody or mizoribine

Myeloperoxidase‐specific anti‐neutrophil cytoplasmic antibody (MPO–ANCA) is associated with rapidly progressive glomerulonephritis (RPGN) and glomerular crescent formation. Pathogenic factors in RPGN were analyzed by using SCG/Kj mice, which spontaneously develop MPO–ANCA‐associated RPGN. The serum concentration of soluble IL‐6R was determined by using ELISA and those of another 23 cytokines and chemokines by Bio‐Plex analysis. Sections of frozen kidney tissue were examined by fluorescence microscopy and the CD3+B220+ T cell subset in the spleen determined by a flow cytometry. Concentrations of IL‐6 and monocyte chemotactic protein‐1 were significantly correlated with the percentages of crescent formation. Anti‐IL‐6R antibody, which has been effective in patients with rheumatoid arthritis, was administered to SCG/Kj mice to elucidate the role of IL‐6 in the development of RPGN. MPO–ANCA titers decreased after administration of anti‐IL‐6R antibody, but not titers of mizoribine, which is effective in Kawasaki disease model mice. These results suggest that IL‐6‐mediated signaling is involved in the production of MPO–ANCA.

The European Vasculitis Society 2016 Meeting Report

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.