[The unusual mimicker of a polymyositis]. / Der außergewöhnliche Nachahmer einer Polymyositis.

This article describes a hantavirus-associated pronounced myositis as a rare differential diagnosis to polymyositis. The literature on the pathogenesis of hantavirus disease discusses less a direct viral cytopathology but more a secondary immune dysregulation with induction of a capillary leak. This article describes for the first time a case of successful treatment of protracted hantavirus myositis using high-dose glucocorticoids and cyclophosphamide, followed by ciclosporin and MTX.

Evaluation of choroidal substructure perfusion in patients affected by systemic sclerosis: an optical coherence tomography angiography study.

Objective: Vasculopathy in systemic sclerosis (SSc) is characterized by the obliteration of arterioles and a reduced capillary density in various tissues. In SSc, atrophic alterations of the choroid have been suggested based on morphological data acquired by optical coherence tomography (OCT). In this study, we aimed to assess the choroid in eyes of patients with SSc from a microcirculatory, dynamic point of view by adding optical coherence tomography angiography (OCTA) to the diagnostic spectrum.Method: SSc patients were enrolled, and age- and gender-matched healthy subjects were used as controls. In addition to basic ophthalmological and rheumatological examinations, individuals underwent enhanced-depth imaging OCT and OCTA. Subfoveal thicknesses of the choroid as well as all three choroidal vascular sublayers were measured and submacular perfusion values were evaluated.Results: In total, 12 patients with SSc and 12 matched controls were included. The median age of participants was 64 years. Submacular perfusion was significantly lower in the choriocapillaris (Δ = 0.72%; p = 0.045), Sattler's layer (Δ = 2.87%; p = 0.001), and Haller's layer (Δ = 2.69%; p = 0.018) of SSc patients compared to controls. Subfoveal thicknesses of Sattler's layer (Δ = 15 µm; p = 0.026) and Haller's layer (Δ = 41 µm; p = 0.045) were also significantly smaller in the SSc group.Conclusion: Choroidal microcirculation is impaired in SSc, even in patients without ophthalmological symptoms. Choroidal OCT and OCTA may offer additional biomarkers for SSc activity.

[Regulatory T cells and rheumatic diseases]. / Regulatorische T-Zellen und rheumatische Erkrankungen.

BACKGROUND: Regulatory T cells (Treg) are crucial for the maintenance of immunological peripheral tolerance by controlling the activation and expansion of autoreactive cells; therefore, they make a decisive contribution to the prevention and control of autoimmune diseases. OBJECTIVES: The aims of this article are to summarize the history and role of Treg in science and medicine, to provide a brief introduction to the development and function, to explain how failures in Treg biology contribute to the development of autoimmune disease, to explain their specific role in particular rheumatic diseases and to provide an introduction to the therapeutic use of Treg in autoimmune diseases. METHODS: Relevant original literature and review articles were analyzed and the results are summarized in this article. RESULTS: Disorders in Treg biology can contribute to the development of rheumatic diseases in various ways. In addition, their capability to suppress autoimmunity renders Treg an attractive target for the treatment of rheumatic diseases. CONCLUSIONS: The concept of Treg-mediated immunoregulation has evolved into an independent field of research in immunology and medicine. First translational approaches and clinical studies confirmed the therapeutic efficacy of Treg in the treatment of autoimmune syndromes.

CXCR3+CD4+ T cells are enriched in inflamed kidneys and urine and provide a new biomarker for acute nephritis flares in systemic lupus erythematosus patients.

OBJECTIVE: The high frequency of CD4+ T cells in interstitial infiltrates of patients with lupus nephritis suggests a contribution of these cells to local pathogenesis. The aim of this study was to examine the role of CXCR3 and the chemokine CXCL10 in recruiting these cells into the kidney and to determine whether the infiltrating T cells could be monitored in the urine to provide a reliable biomarker for acute lupus nephritis. METHODS: The frequencies of CD3+ T cells, CXCR3+ cells, and CXCL10+ cells were determined by immunohistochemical and immunofluorescence analyses of kidney sections from 18 patients with lupus nephritis. The frequency of CXCR3+CD4+ T cells was determined by flow cytometry of peripheral blood and urine from 38 patients with systemic lupus erythematosus (SLE), and the values were compared with disease activity as determined by the Systemic Lupus Erythematosus Disease Activity Index. RESULTS: In renal biopsy tissues from patients with lupus nephritis, a mean of 63% of the infiltrating cells expressed CXCR3, approximately 60% of them were T cells, and the CXCR3+ cells colocalized with CXCL10-producing cells. In biopsy tissues from SLE patients with acute nephritis, approximately 50% of the urinary CD4+ T cells were CXCR3+, as compared with 22% in the peripheral blood, and the frequency of urinary CXCR3+CD4+ T cells correlated with disease activity. Moreover, the number of urinary CD4+ T cells reflected nephritis activity, and elevation above 800 CD4+ T cells per 100 ml of urine sharply delineated active from inactive nephritis. CONCLUSION: CXCR3+ T cells are recruited into the inflamed kidneys, are enriched in the urine, and are a valuable marker of nephritis activity in SLE. They also present a potential target for future therapies.

The highly attenuated vaccinia virus strain modified virus Ankara induces apoptosis in melanoma cells and allows bystander dendritic cells to generate a potent anti-tumoral immunity.

Vaccinia virus (VV) has been tested as oncolytic virus against malignant melanoma in clinical trials for more than 40 years. Until now, mainly strains comparable to viral strains used for smallpox vaccination have been probed for anti-tumoral therapy. We have shown recently that the wild-type strain Western Reserve (WR) can interfere with crucial functions of monocyte-derived dendritic cells (DCs). Our aim was to examine whether viral immune evasion mechanisms might be responsible for the ineffectiveness of WR-based vaccination strategies and whether the highly attenuated strain modified virus Ankara (MVA) differs from WR with respect to its possible immunostimulatory capacity after intratumoral injection. Using in vitro experiments, we compared the effect of both strains on melanoma cells and on local bystander DCs. We found that both VV-strains infected melanoma cells efficiently and caused disintegration of the actin cytoskeleton, as shown by fluorescence microscopy. In addition, both VV-strains caused apoptotic cell death in melanoma cells after infection. In contrast to MVA, WR underwent a complete viral replication cycle in melanoma cells. Bystander DCs were consecutively infected by newly generated WR virions and lost their capacity to induce allogeneic T cell proliferation. DCs in contact with MVA-infected melanoma cells retained their capacity to induce T cell proliferation. Immature DCs were capable of phagocytosing MVA-infected melanoma cells. Priming of autologous CD8(+) T cells by DCs that had phagocytosed MVA-infected, MelanA positive melanoma cells resulted in the induction of T cell clones specifically reactive against the model antigen MelanA as shown by enzyme-linked immunospot (ELISPOT) analysis. We conclude that the clinical trials with oncolytic wild-type VV failed probably because of suppression of bystander DCs and consecutive suppression of T cell-mediated anti-melanoma immunity. The attenuated VV-strain MVA facilitates the generation of tumour associated antigen (TAA)-specific T cell response as it is oncolytic for melanoma cells, but non-toxic for DC, and should be a promising candidate for intralesional metastatic melanoma therapy.