PubMed Health⌕ Search

Biomedical subjects

Hans-Peter Hartung

Publications and source records attributed to Hans-Peter Hartung.

At least 19 recordsLinked to original sources
PubMed2007

CD8 T-cell subsets and viral load in the cerebrospinal fluid of therapy-naive HIV-infected individuals.

Central nervous system involvement is common in HIV infection. We determined the relationship between T-cell subsets and viral load in the cerebrospinal fluid (CSF) of therapy-naive, asymptomatic HIV-infected individuals. A shift from naive to effector-memory CD8 T cells was observed in the CSF of HIV-infected individuals compared with controls. The HIV load strongly correlated with CD8 T cells in CSF. Effector-memory CD8 T cells were positively and effector CD8 T cells were negatively associated with viral replication in CSF.

CD8-Positive T-Lymphocytes↗
PubMed2007

The cell-specific expression of metalloproteinase-disintegrins (ADAMs) in inflammatory myopathies.

Inflammatory cell invasion and cytokine activation are important steps in the pathogenesis of immune-mediated diseases of muscle. Metalloproteinase-disintegrins (ADAMs) are considered to play a critical role in leukocyte migration by promoting cellular adhesion, cleavage of molecules of the extracellular matrix and shedding of membrane bound cytokines. Here, we report the expression patterns of ADAM8, ADAM9, ADAM10, ADAM12, ADAM17 and ADAM19 in cultured human myoblasts and peripheral blood mononuclear cells (PBMCs) in vitro, as well as in biopsies from patients suffering from polymyositis (PM), dermatomyositis (DM), inclusion body myositis (IBM) and non-inflammatory controls. We observed an in vitro downregulation of the RNAs of ADAM10, ADAM17 and ADAM19 in myoblasts after stimulation with various pro- and anti-inflammatory mediators, whereas in PBMCs an RNA upregulation of ADAM9, ADAM10, ADAM17 and ADAM19 was detectable under identical conditions. In human muscle biopsies, invading CD3+ T lymphocytes expressed ADAM17 and ADAM19, whereas macrophages co-localized to ADAM8, as detected by immunohistochemistry. Transfection of PBMCs with ADAM19 single interfering RNA and incubation with a metalloproteinase inhibitor suggest proteolytic activity of ADAM19 and involvement in the shedding of tumor necrosis factor-alpha. No differences in the cellular expression profiles between PM, DM and IBM were found, whereas the sections from non-inflammatory controls did not reveal any positive immunoreactivity for ADAMs, except for ADAM10, which is localized exclusively to muscle fibres. Our results suggest that certain ADAMs are expressed by specific cell populations during the genesis of immune-mediated diseases of human muscle.

ADAM Proteins↗
PubMed2006

Identification of a pathogenic antibody response to native myelin oligodendrocyte glycoprotein in multiple sclerosis.

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system. Although the cause of MS is still uncertain, many findings point toward an ongoing autoimmune response to myelin antigens. Because of its location on the outer surface of the myelin sheath and its pathogenicity in the experimental autoimmune encephalomyelitis model, myelin oligodendrocyte glycoprotein (MOG) is one of the potential disease-causing self antigens in MS. However, the role of MOG in the pathogenesis of MS has remained controversial. In this study we addressed the occurrence of autoantibodies to native MOG and its implication for demyelination and axonal loss in MS. We applied a high-sensitivity bioassay, which allowed detecting autoantibodies that bind to the extracellular part of native MOG. Antibodies, mostly IgG, were found in sera that bound with high affinity to strictly conformational epitopes of the extracellular domain of MOG. IgG but not IgM antibody titers to native MOG were significantly higher in MS patients compared with different control groups with the highest prevalence in primary progressive MS patients. Serum autoantibodies to native MOG induced death of MOG-expressing target cells in vitro. Serum from MS patients with high anti-MOG antibody titers stained white matter myelin in rat brain and enhanced demyelination and axonal damage when transferred to autoimmune encephalomyelitis animals. Overall these findings suggest a pathogenic antibody response to native MOG in a subgroup of MS patients.

Animals↗
PubMed2006

Increased thalamic neurodegeneration following ischaemic cortical stroke in osteopontin-deficient mice.

Inflammation aggravates brain injury caused by stroke and neurodegeneration. Osteopontin (OPN) is a cytokine-like glycoprotein that binds to various integrins and CD44 variants. OPN exerts proinflammatory effects in autoimmune conditions but also has cytoprotective properties and participates in wound healing. In this study, we addressed the role of OPN in ischaemic brain injury using OPN knock-out (KO) mice in models of cortical stroke. Compared with wild-type animals, OPN KO mice exhibited unaltered infarct development at the primary injury site but greatly increased retrograde degeneration of the ipsilateral thalamus. Thalamic neurodegeneration in OPN-deficient mice was associated with pronounced microglia activation and inflammatory gene expression and could be attenuated via pharmacological blockade of the inducible nitric oxide synthase (iNOS). Therefore, delayed neurodegeneration in OPN-deficient mice was at least partly due to an excessive release of nitric oxide via the iNOS pathway. Neuroprotective and anti-inflammatory effects of OPN may be relevant for a variety of neurological disease conditions.

Animals↗
PubMed2006

Inhibition by mitoxantrone of in vitro migration of immunocompetent cells: a possible mechanism for therapeutic efficacy in the treatment of multiple sclerosis.

BACKGROUND: Damage of the blood-brain barrier and invasion of immunocompetent cells into the central nervous system represent key events in the immunopathogenesis of multiple sclerosis. Mitoxantrone hydrochloride reduces progression of disability and clinical exacerbations in patients with multiple sclerosis. Its precise mode of action is unclear. OBJECTIVE: To investigate the effects of mitoxantrone on the migratory capacity of immunocompetent cells ex vivo and in vitro. DESIGN: Case-control study. SETTING: Department of Neurology, Heinrich Heine University, Düsseldorf, Germany. PARTICIPANTS: Peripheral blood mononuclear cells (PBMCs) were obtained from 11 patients with multiple sclerosis before and after intravenous mitoxantrone treatment; PBMCs from 5 healthy control donors were treated with mitoxantrone in vitro. MAIN OUTCOME MEASURES: The migratory capacity was studied in an in vitro Boyden chamber assay; cells and their rates of migration were analyzed by light microscopy and flow cytometry. To determine the specificity of our findings, PBMCs were treated with perfosfamide in vitro. RESULTS: Mitoxantrone decreased the migratory capacity of CD14(+) monocytes and (to a lesser degree) of CD4(+) and CD8(+) T lymphocytes. These observations were confirmed when control PBMCs were treated with an equivalent dose of mitoxantrone in vitro. Similar effects were seen when PBMCs were preincubated with perfosfamide. The inhibitory effects of mitoxantrone on the migratory capacity of PBMCs were mediated by reduced matrix metalloproteinase 9 activity, as demonstrated by zymography, polymerase chain reaction, and inhibitory studies. CONCLUSION: Mitoxantrone may inhibit the migration of inflammatory cells into and within the central nervous system.

Adult↗
PubMed2006

Interleukin 23 in acute inflammatory demyelination of the peripheral nerve.

BACKGROUND: Interleukin (IL) 23, a newly identified heterodimeric proinflammatory cytokine and a novel IL-12 family member comprising the p40 subunit of IL-12 but a different p19 subunit, has been reported to preferentially act on memory T cells and play an important role during cellular immune responses. Recent evidence suggests that IL-23 rather than IL-12 is critically involved in the pathogenesis of various immune-mediated disorders. OBJECTIVE: To determine the role of IL-23p19 during the course of acute immune-mediated demyelinating diseases of the peripheral nervous system. DESIGN: The sequential RNA expression of IL-23p19 in sciatic nerves from rats with experimental autoimmune neuritis, an animal model of the human Guillain-Barré syndrome (GBS), was analyzed by semiquantitative reverse transcriptase-polymerase chain reaction. Expression and distribution patterns of IL-23p19 protein were studied in sural nerve biopsies and cerebrospinal fluid samples from 5 patients with classical Guillain-Barré syndrome and 5 controls with noninflammatory neuropathies using immunohistochemistry and immunoblotting, respectively. RESULTS: We found IL-23p19 RNA to be up-regulated prior to the onset of first clinical symptoms with peak expression levels preceding maximum disease severity during experimental autoimmune neuritis. In patients, IL-23p19 protein was detectable in cerebrospinal fluid samples from patients with Guillain-Barré syndrome, and endoneurial macrophages were identified as the cellular source of IL-23p19 in sural nerve biopsies. CONCLUSION: Our present data indicate that IL-23 may play an important role during the early effector phase in immune-mediated demyelination of the peripheral nerve.

Animals↗
PubMed2006

Plasma exchange in neuroimmunological disorders: Part 1: Rationale and treatment of inflammatory central nervous system disorders.

Plasma exchange is a well-established therapeutic procedure commonly used in many neurological disorders of autoimmune etiology. It is thought that the beneficial effects of plasma exchange occur through the elimination of pathognomonic inflammatory mediators, including autoantibodies, complement components, and cytokines. In various neurological disorders, randomized controlled studies have demonstrated the efficacy of plasma exchange (eg, in Guillain-Barré syndrome and other forms of immune neuropathies). Although widely used, the potential benefit of plasma exchange in the treatment of multiple sclerosis, myasthenia gravis, and Lambert-Eaton syndrome is less clear.

Central Nervous System Diseases↗
PubMed2006

Plasma exchange in neuroimmunological disorders: part 2. Treatment of neuromuscular disorders.

Plasma exchange is a well-established therapeutic procedure commonly used in many neurological disorders of autoimmune etiology. In this second part of our review, we assess the role of plasma exchange in the treatment of neuromuscular disorders. In Guillain-Barré syndrome and other immune-mediated neuropathic disorders, randomized controlled trials have demonstrated the therapeutic efficacy of plasma exchange. Myasthenia gravis and Lambert-Eaton syndrome represent neuromuscular disorders where plasmapheresis might be of potential efficacy.

Autoimmune Diseases of the Nervous System↗
PubMed2006

Mycophenolate mofetil and tacrolimus: new therapeutic options in neuroimmunological diseases.

Mycophenolate mofetil (MMF) and tacrolimus are novel immunosuppressive drugs, both first established in transplantation medicine and now used increasingly in neuroimmunological diseases including myasthenia gravis, dysimmune polyneuropathies, and myositis. In myasthenia gravis, the efficacy and safety of MMF has been shown by one open-label trial; one small, double-blind, placebo-controlled trial; and a few retrospective analyses. Similarly, for tacrolimus the greatest experience and evidence for efficacy and safety have been gathered in myasthenia gravis. MMF and tacrolimus have both been used as an alternative treatment for various other autoimmune diseases in which azathioprine or cyclosporine were not sufficiently effective. However, experience with tacrolimus in dysimmune polyneuropathies and myositis is limited. At this time, the available data suggest that MMF and tacrolimus are well suited for long-term immunosuppression in patients with myasthenia gravis. The spectrum of neuroimmunological diseases in which these drugs may be used has not been finally delineated and will require further controlled studies.

Autoimmune Diseases of the Nervous System↗
PubMed2006

High throughput analysis of TCR-beta rearrangement and gene expression in single T cells.

Analysis of T-cell receptor beta chain (TCR-beta) rearrangement is essential to investigate T-cell responses in human autoimmune diseases, infection and cancer. Since the TCR-beta locus contains 55 variable (V) region gene segments, multiple assays have been necessary to determine TCR-beta rearrangements of individual T cells. We established a seminested rtPCR method for single T-cell analysis with two sets of degenerate primers covering 76 and 24% of the TCR-Vbeta genes, respectively. The specificity of the approach was validated by screening cDNAs obtained from T-cell clones (TCC) with defined TCR-beta rearrangement. We applied the method successfully to profile TCR-beta rearrangement of single T cells sorted from body fluids or dissected tissue. Concomitant analysis of other gene transcripts allowed determining phenotype and function of TCR-beta-defined single T cells. Our fast, cost-efficient and high throughput approach will facilitate studies on T-cell responses in human diseases.

Brain Neoplasms↗
PubMed2006

Immunopathogenesis and immunotherapy of multiple sclerosis.

Multiple sclerosis (MS) is a chronic disease of the CNS that is characterized by inflammation, demyelination and axonal injury. Although the etiology of MS is still unknown, many findings point toward a central role for the immune system in the pathogenesis of the disease. This hypothesis is strongly supported by the beneficial effects of immunomodulatory and immunosuppressive therapy on disease activity. Over the past few years, substantial progress has been made in deciphering the immune response in MS. Although animal models have advanced our knowledge of basic mechanisms of immune responses in the CNS, recent studies have also highlighted the differences between MS and its animal equivalent, experimental autoimmune encephalomyelitis. New immunotherapeutic agents have been developed and evaluated in clinical trials. Here, we review current knowledge of the immunopathogenesis of MS and corresponding animal models of disease, and discuss new immunointerventional treatment strategies based on changing pathogenetic concepts.

Animals↗
PubMed2006

Immune circuitry in the peripheral nervous system.

PURPOSE OF REVIEW: The aim of this review is to describe the local immune circuitry in the peripheral nervous system and its dialogue with systemic immunity under pathological conditions. Specifically, interactions of the immune system with cellular and extracellular components within peripheral nerve and immune functions of tissue-resident endoneurial macrophages and Schwann cells will be discussed. RECENT FINDINGS: New insights into the elements involved in the pathogenesis of immune-mediated disorders of the peripheral nervous system provide a better understanding of the complex interplay of these cellular and molecular components in the immunology of the peripheral nervous system. SUMMARY: The application of innovative and cutting-edge technologies to the study of immunoinflammatory disorders of the peripheral nervous system provides a better understanding of underlying principles of the organization of the immune network present in the peripheral nerve and its dialogue with the systemic immune system. This may foster the development of specific and highly effective therapies for immune-mediated disorders of the peripheral nerve.

Animals↗