Biomedical subjects

Rüdiger Eming

Publications and source records attributed to Rüdiger Eming.

6 recordsLinked to original sources

PubMed2006

Detection of low avidity desmoglein 3-reactive T cells in pemphigus vulgaris using HLA-DR beta 1*0402 tetramers.

In the present study, we developed a HLA class II tetramer-based detection system utilizing DRB1*0402 tetramers loaded with recently identified immunodominant peptides of desmoglein 3 (Dsg3), the major autoantigen of pemphigus vulgaris (PV). Initial experiments demonstrated staining of a Dsg3-reactive T cell hybridoma which was derived from HLA-DR0402-transgenic mice with loaded PE-labeled DRbeta1*0402 tetramers. However, staining of autoreactive T cell clones (TCC) derived from PV patients resulted only in positive staining by addition of exogenous peptides to the staining reactions. There was a dose-dependent specific binding of TCC to the tetramers with the agonistic Dsg3 peptide which was not altered by exogenous unrelated Dsg3 peptide. Noteworthy, the TCC did not stain with HLA-DR4 tetramers complexed with unrelated Dsg3 peptides. The findings of this study suggest that HLA class II tetramers may provide a highly specific approach to monitor ex vivo the T cellular autoimmune response against Dsg3 in patients with PV.

Alleles↗

PubMed2006

Immunoadsorption in pemphigus.

The principle of extracorporal immunoadsorption (IA) is based on affinity adsorption of pathogenic (auto-)antibodies and circulating immune complexes (CIC) which reversibly bind to an immobilized ligand of the adsorber. In pemphigus, a blistering autoimmune disease affecting skin and mucous membranes, autoantibodies, mainly of the IgG subclass are directed against desmosomal adhesion molecules and other non-desmosomal antigens on the surface of epidermal keratinocytes, such as acetylcholine receptors. The pathogenicity of these autoantibodies has been shown in various in vitro and in vivo systems. Recently, IA was applied in severe pemphigus demonstrating that a rapid and dramatic decline in desmoglein (Dsg)-reactive autoantibodies is accompanied by clinical remission of mucocutaneous blisters and erosions. As an adjuvant treatment, IA was combined with systemic immunosuppressive medication and current protocols initially apply treatment cycles of 3-4 IAs on consecutive days followed by immunoapheresis once a week or repeating the initial cycle in 4 week intervals depending on the disease activity. IA in pemphigus is generally safe and well tolerated.

Animals↗

PubMed2006

Prolonged clinical remission of patients with severe pemphigus upon rapid removal of desmoglein-reactive autoantibodies by immunoadsorption.

BACKGROUND: In pemphigus, loss of epidermal adhesion is induced by binding of circulating autoantibodies to the desmosomal cadherins desmoglein 3 (Dsg3) in pemphigus vulgaris (PV) and desmoglein 1 (Dsg1) in pemphigus foliaceus (PF), respectively. Therapeutic removal of Dsg-reactive autoantibodies by immunoadsorption (IA) has been demonstrated to exert clinical remission of the disease. OBJECTIVES: The aim of this intervention study was to evaluate the efficacy and safety of the peptide-based Globaffin adsorber system in the treatment of severe pemphigus cases. PATIENTS AND METHODS: We applied IA in 4 PV and 2 PF patients with severe chronic disease resistant to conventional immunosuppressive therapy. IA was performed on 4 consecutive days, representing 1 treatment cycle, followed by a 4-week treatment-free interval. Serum samples for determining serum IgG and anti-Dsg1/Dsg3 IgG autoantibodies were drawn daily before and after IA, respectively. During follow-up, patients were examined carefully, and laboratory parameters were controlled monthly for up to 1 year. RESULTS: IA led to excellent clinical responses. Skin and mucosal lesions cleared almost completely within weeks. One IA cycle reduced anti-Dsg1 and anti-Dsg3 autoantibodies by an average of 50-70% as determined by ELISA. CONCLUSIONS: Using the Globaffin adsorber system, IA represents an effective and safe treatment opportunity in severe and therapy-resistant pemphigus.

Adult↗

PubMed2006

T cell control in autoimmune bullous skin disorders.

Autoimmune bullous disorders are a group of severe skin diseases characterized clinically by blisters and erosions of skin and/or mucous membranes. A hallmark of these disorders is the presence of IgG and occasionally IgA autoantibodies that target distinct adhesion structures of the epidermis, dermoepidermal basement membrane, and anchoring fibrils of the dermis. This Review focuses on the potential role of autoreactive T cells in the pathogenesis of these disorders. Pemphigus vulgaris (PV) and bullous pemphigoid (BP) are the best-characterized bullous disorders with regard to pathogenesis and T cell involvement. Activation of autoreactive T cells in PV and BP is restricted by distinct HLA class II alleles that are prevalent in individuals with these disorders. Autoreactive T cells are not only present in patients but can also be detected in healthy individuals. Recently, a subset of autoreactive T cells with remarkable regulatory function was identified in healthy individuals and to a much lesser extent in patients with PV, suggesting that the occurrence of autoimmune bullous disorders may be linked to a dysfunction of Tregs.

Animals↗

PubMed2006

Autoimmune bullous disorders.

Bullous skin diseases represent a group of organ-specific autoimmune disorders characterised by binding of circulating autoantibodies to adhesion molecules of the epidermis and the dermo-epidermal basement membrane zone. Binding of these autoantibodies to their antigenic targets results in loss of adhesion between epidermal keratinocytes and at the level of the basement membrane zone. Chronic blisters and secondary painful erosions are the clinical hallmark of autoimmune bullous disorders. Histopathology reveals the location of blister formation and helps to classify the subtype of the bullous skin disorder. Immunofluorescence is crucial for diagnosing autoimmune bullous skin disorders. Tissue-bound autoantibodies are detected by direct immunofluorescence of perilesional skin. Circulating autoantibodies can be visualised by indirect immunofluorescence using tissue substrates such as monkey oesophagus and sodium chloride-split human skin. Most of the autoantigens are available as recombinant proteins, which allows for autoantibody screening by ELISA or immunoblot analysis to confirm the primary diagnosis and, importantly, for immunoserological follow-up of patients.

Autoantibodies↗

PubMed2002

Humanized mice as a model for rheumatoid arthritis.

Genetic susceptibility to rheumatoid arthritis (RA), a common autoimmune disease, is associated with certain HLA-DR4 alleles. Treatments are rarely curative and are often tied to major side effects. We describe the development of a humanized mouse model wherein new, less toxic, vaccine-like treatments for RA might be pretested. This model includes four separate transgenes: HLA-DR*0401 and human CD4 molecules, a RA-related human autoantigenic protein (HCgp-39), and a T-cell receptor (TCRalphabeta) transgene specific for an important HCgp-39 epitope, eliciting strong Th1 responses in the context of HLA-DR*0401.

Animals↗