The effect of HIV coinfection, HAART and TB treatment on cytokine/chemokine responses to Mycobacterium tuberculosis (Mtb) antigens in active TB patients and latently Mtb infected individuals.

Identification of Mtb specific induced cytokine/chemokine host biomarkers could assist in developing novel diagnostic, prognostic and therapeutic tools for TB. Levels of IFN-γ, IL-2, IL-17, IL-10, IP-10 and MIP-1α were measured in supernatants of whole blood stimulated with Mtb specific fusion protein ESAT-6/CFP-10 using xMAP technology. The study groups were HIV positive TB patients (HIV(+)TB(+)), HIV negative TB patients (HIV(-)TB(+)), HIV positive tuberculin skin test positive (TST+) (HIV(+)TST(+)), HIV negative TST+ (HIV(-)TST(+)), and HIV(-)TST(-) individuals.

Complementary role of HCV and HIV in T-cell activation and exhaustion in HIV/HCV coinfection.

Objectives: To investigate whether T-cell activation and exhaustion is linked to HCV- and HIV disease parameters in HIV/HCV infected individuals, we studied T-cell characteristics in HIV/HCV coinfected patients and controls.

Methods: 14 HIV/HCV coinfected, 19 HCV monoinfected, 10 HIV monoinfected patients and 15 healthy controls were included in this cross-sectional study. Differences in expression of activation and exhaustion markers (HLA-DR, CD38, PD-1, Tim-3 and Fas) and phenotypic markers on CD4(+) and CD8(+) T-cells were analysed by flow cytometry and were related to HCV disease parameters (HCV-viremia, ALT and liver fibrosis).

Effect of administration of apoptotic blebs on disease development in lupus mice.

Introduction: Systemic lupus erythematosus (SLE) is an autoimmune disease characterised by the formation of autoantibodies against nuclear components. Disturbed apoptosis and reduced clearance of apoptotic material have been assigned a role in the pathogenesis of SLE. During apoptosis, apoptotic blebs are formed, in which SLE autoantigens are clustered.

Pegylated interferon-α monotherapy leads to low response rates in HIV-infected patients with acute hepatitis C.

Background: Despite a rising incidence of acute HCV in patients infected with HIV, the optimal therapeutic strategy (pegylated interferon-α [PEG-IFN-α] monotherapy or in combination with ribavirin) is still under debate.

Methods: A total of 23 HIV-infected patients were prospectively diagnosed with acute HCV and treated with PEG-IFN-α2a monotherapy (180 μg/week) for 24 or 48 weeks. Add-on ribavirin was allowed from week 4 of therapy onwards.

Association between IL28B polymorphisms and first-phase viral load decrease in chronic hepatitis C virus-infected patients treated with peginterferon alfa-2b/ribavirin.

Host polymorphisms in the IL28B region have recently been associated with outcome of treatment for hepatitis C virus (HCV) infection. This study clearly shows an association between first-phase viral load decrease and the IL28B rs12979860 polymorphism in chronic HCV-infected patients. Furthermore, a higher treatment efficiency factor (ɛ) was found in those HCV-infected patients with a CC genotype compared with those with a CT and TT genotype.

The role of dendritic cells in the pathogenesis of systemic lupus erythematosus.

The etiology of the autoimmune disease systemic lupus erythematosus is not known, but aberrant apoptosis and/or insufficient clearance of apoptotic material have been assigned a pivotal role. During apoptosis, nucleosomes and several endogenous danger-associated molecular patterns are incorporated in blebs. Recent data indicate that apoptotic blebs induce maturation of myeloid dendritic cells, resulting in IL-17 production by T cells.

Mouse dendritic cells matured by ingestion of apoptotic blebs induce T cells to produce interleukin-17.

Objective: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the formation of antinuclear autoantibodies. Increased apoptosis and reduced clearance of apoptotic material have been assigned a role in the pathogenesis of SLE, but the underlying mechanisms remain elusive. During apoptosis apoptotic blebs are formed in which autoantigens are clustered.

Apoptosis-induced acetylation of histones is pathogenic in systemic lupus erythematosus.

Objective: In systemic lupus erythematosus (SLE), inadequate removal of apoptotic cells may lead to challenge of the immune system with immunogenic self antigens that have been modified during apoptosis. We undertook this study to evaluate whether apoptosis-induced histone modifications are targets for the immune system in SLE.

Methods: The epitope of KM-2, a monoclonal antihistone autoantibody derived from a lupus mouse, was mapped by random peptide phage display.

The interferon gamma gene in celiac disease: augmented expression correlates with tissue damage but no evidence for genetic susceptibility.

Celiac disease (CD) is a complex genetic disorder characterized by gluten intolerance. The Th1 immune response, with a key position for interferon gamma (IFN-gamma), is an important determinant of intestinal remodeling in CD. We aimed at further ascertaining the role of IFN-gamma, either as a genetic factor in the etiology, or as a facilitator of disease initiation/progression.