New insights into pathogenesis and treatment of anca-associated vasculitis. autoantibodies and beyond

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a group of rare systemic diseases affecting small-caliber vessels. The damage caused by AAV mainly involves the lung and kidneys. AAV includes three different types: granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). Although the different phenotypic forms of AAV share common features, recent studies have shown that there are significant differences in terms of pathogenetic mechanisms involving both the adaptive and innate immune systems. Advances in our understanding of pathogenesis have enabled the development of immuno-targeted therapies. This review illustrates the characteristics of the various forms of AAV and the new therapies available for this disease that can have lethal consequences if left untreated

Chloroquine enhances human CD8+ T cell responses against soluble antigens in vivo

The presentation of exogenous protein antigens in a major histocompatibility complex class I–restricted fashion to CD8+ T cells is called cross-presentation. We demonstrate that cross-presentation of soluble viral antigens (derived from hepatitis C virus [HCV], hepatitis B virus [HBV], or human immunodeficiency virus) to specific CD8+ T cell clones is dramatically improved when antigen-presenting dendritic cells (DCs) are pulsed with the antigen in the presence of chloroquine or ammonium chloride, which reduce acidification of the endocytic system. The export of soluble antigen into the cytosol is considerably higher in chloroquine-treated than in untreated DCs, as detected by confocal microscopy of cultured cells and Western blot analysis comparing endocytic and cytosolic fractions. To pursue our findings in an in vivo setting, we boosted groups of HBV vaccine responder individuals with a further dose of hepatitis B envelope protein vaccine with or without a single dose of chloroquine. Although all individuals showed a boost in antibody titers to HBV, six of nine individuals who were administered chloroquine showed a substantial CD8+ T cell response to HBV antigen, whereas zero of eight without chloroquine lacked a CD8 response. Our results suggest that chloroquine treatment improves CD8 immunity during vaccination

Apoptotic epitope-specific CD8+ T cells and interferon signaling intersect in chronic hepatitis C virus infection

CD8(+) T cells specific to caspase-cleaved antigens derived from apoptotic T cells represent a principal player in chronic immune activation (CIA). Here, we found that both apoptotic epitope (AE)-specific and hepatitis C virus (HCV)-specific CD8(+) T cells were mostly confined within the effector memory (EM) or terminally differentiated EM CD45RA(+) cell subsets expressing a dysfunctional T-helper-1-like signature program in chronic (c)HCV infection. However, AE-specific CD8(+) T cells produced tumor necrosis factor (TNF)-α and interleukin-2 at the intrahepatic level significantly more than HCV-specific CD8(+) T cells, despite both populations acquiring high levels of programmed death-1 receptor expression. Contextually, only AE-specific CD8(+) T cells correlated with both interferon-stimulated gene levels in T cells and hepatic fibrosis score. Taken together, these data suggest that AE-specific CD8(+) T cells can sustain CIA by their capacity to produce TNF-α and be resistant to inhibitory signals more than HCV-specific CD8(+) T cells in cHCV infection

Polyfunctional Type-1, -2, and -17 CD8+ T Cell Responses to Apoptotic Self-Antigens Correlate with the Chronic Evolution of Hepatitis C Virus Infection

Caspase-dependent cleavage of antigens associated with apoptotic cells plays a prominent role in the generation of CD8+ T cell responses in various infectious diseases. We found that the emergence of a large population of autoreactive CD8+ T effector cells specific for apoptotic T cell-associated self-epitopes exceeds the antiviral responses in patients with acute hepatitis C virus infection. Importantly, they endow mixed polyfunctional type-1, type-2 and type-17 responses and correlate with the chronic progression of infection. This evolution is related to the selection of autoreactive CD8+ T cells with higher T cell receptor avidity, whereas those with lower avidity undergo prompt contraction in patients who clear infection. These findings demonstrate a previously undescribed strict link between the emergence of high frequencies of mixed autoreactive CD8+ T cells producing a broad array of cytokines (IFN-γ, IL-17, IL-4, IL-2…) and the progression toward chronic disease in a human model of acute infection

Hepatitis C virus infection and autoimmune diseases

Hepatitis C virus (HCV) infection is associated with a number of extrahepatic disorders. The most studied conditions associated with HCV are type II mixed cryoglobulinemia and B cell lymphoma. However, many reports suggest that HCV might also be associated with a number of autoimmune disorders, both organ-specific and not organ-specific. Although concomitant treatment of HCV infection is a confounding factor when ascertaining the actual role of HCV in inducing autoimmune disease, a considerable amount of experimental data indicates that HCV is able to subvert the immune system and consequently induce autoimmunity. In the present review, we report a series of observations which associate chronic HCV infection with the onset of autoimmune disorders. © 2012 Paroli et al, publisher and licensee Dove Medical Press Ltd

VIRUS ESCAPE FROM IMMUNE CONTROL - MECHANISMS OF PERSISTENCE WITHIN THE HOST

[No abstract available

A rare case of reactive arthritis associated with Enterobius vermicularis infection

[No abstract available

Churg-Strauss syndrome associated with antiphospholipid antibodies in a patient with recurrent myocardial and cerebral ischemia

We report on a case of Churg-Strauss syndrome (CSS) associated with the presence of antiphospholipid antibodies. The patient had a history of recurrent myocardial infarction and presented with acute ischemic cerebral disease. Eosinophilia with typical lung and skin lesions led us to diagnose the patient with CCS. We hypothesize that the presence of antiphospholipid antibodies significantly contributed to the ischemic events. We suggest that the search for antiphospholipid antibodies should be included in the laboratory work-up in CSS patients and patients affected by primary systemic vasculitides in general. Moreover, anticoagulant treatment appears to be warranted in all CSS patients and antiphospholipid antibodies to counteract this thrombosis-favoring association. © 2012 Paroli et al, publisher and licensee Dove Medical Press Ltd

Hepatitis C flare due to superinfection by genotype 4 in an HCV genotype 1b chronic carrier

We report here on a patient affected by chronic hepatitis C who developed acute hepatitis C virus (HCV) superinfection with replacement of genotype 1 b by genotype 4. The history revealed no risk factors for a new exposure to HCV, with the exception of colonoscopy with mucosal biopsy performed about 3 months before. This report underlines the absence of an effective immune-mediated cross-protection against different HCV genotypes. Moreover, the possible relationship between HCV infection and colonoscopy points out the importance of strict adherence to international guidelines for disinfection and cleaning of invasive diagnostic tools for all subjects examined, including HCV chronic carriers. (C) 2002 Lippincott Williams Wilkins

Cardiac abnormalities in a patient with localized scleroderma

[No abstract available