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Target Autoantigen (target + autoantigen)

Distribution by Scientific Domains

Medical Sciences	100%

Selected Abstracts

Desmoglein-3 is a target autoantigen in spontaneous canine pemphigus vulgaris

EXPERIMENTAL DERMATOLOGY, Issue 2 2003
Thierry Olivry
Abstract: Pemphigus vulgaris (PV) is an autoimmune blistering skin disease of humans and companion animals. In human patients, PV is associated with the production of IgG autoantibodies specific for keratinocyte desmosomal glycoproteins of the cadherin family. The purpose of this study was to determine whether antikeratinocyte IgG autoantibodies were present in the skin and serum of dogs with PV, and also to identify the canine PV autoantigen(s) targeted by circulating autoantibodies. Eleven dogs were selected because of the microscopic demonstration of suprabasal epithelial acantholysis. Direct immunofluorescence revealed the presence of IgG autoantibodies bound to the membrane of keratinocytes in skin biopsy specimens of 8/9 dogs (89%). Using indirect immunofluorescence, serum-circulating IgG autoantibodies were found in 10/11 (91%) and 5/11 (45%) dogs, using normal canine gingiva and cultured canine oral keratinocytes, respectively. By immunoblotting using cultured canine oral keratinocyte protein lysates, IgG autoantibodies from 7/9 (78%) tested dogs recognized a 130-kDa antigen that comigrated with that identified by rabbit polyclonal antibodies raised against desmoglein-3. This 130 kDa antigen was confirmed to represent the canine equivalent of human desmoglein-3 by immunoprecipitation-immunoblotting. The results of these studies provide evidence that the canine desmoglein-3 homologue is a major autoantigen in dogs with PV. These observations further establish spontaneous canine PV as a natural model for research on pathogenesis, etiology and novel therapeutic approaches for this disease of humans. [source]

Mycobacterial Hsp65-IgG,expressing tolerogenic B cells confer protection against adjuvant-induced arthritis in Lewis rats

ARTHRITIS & RHEUMATISM, Issue 5 2007
Shailesh R. Satpute
Objective Tolerization of T cells directed against a target autoantigen is a desired goal of experimental approaches for the treatment of autoimmune diseases, and novel and improved methods of tolerance induction are continuously being sought. Because most traditional methods of tolerance induction using soluble antigen are effective in the prevention of autoimmunity but fail to control established disease, this study was carried out to explore an innovative tolerogenic approach for the treatment of ongoing disease, using the rat adjuvant-induced arthritis (AIA) model of human rheumatoid arthritis. Methods Lewis (RT.1l) rats were injected subcutaneously with heat-killed Mycobacterium tuberculosis H37Ra to induce AIA. Before or after AIA induction, Lewis rats were treated intraperitoneally (IP) with tolerogenic B cells expressing a fusion construct of mycobacterial 65-kd heat-shock protein (Hsp65) and IgG heavy-chain. For comparison, control rats were treated IP with ovalbumin (OVA),IgG,expressing B cells or soluble mycobacterial Hsp65, and the effects on AIA were observed. We also tested the immune response to mycobacterial Hsp65 in B cell,tolerized rats. Results Administration of tolerogenic mycobacterial Hsp65,expressing B cells as well as soluble mycobacterial Hsp65, but not OVA-expressing B cells, resulted in a significant decrease in the severity of subsequent AIA. However, in rats with established disease, only the B cell regimen of mycobacterial Hsp65, but not the soluble antigen, suppressed ongoing AIA. Conclusion Mycobacterial Hsp65-IgG,expressing B cells can successfully attenuate the progression of AIA. This study introduces a promising approach for the treatment of arthritis that should be further explored. [source]

PL1 Subepithelial bullous diseases , topic overview

ORAL DISEASES, Issue 2006
M Mravak-Stipeti
Subepithelial bullous diseases comprise the group of mucocutaneous autoimmune blistering diseases characterized by subepithelial separation and the deposition of immunoglobulin and complement against several antigens along the basement membrane zone (BMZ). This result in spectrum of diseases that affect skin, oral mucosa, and other mucosal membranes and include bullous pemphigoid (BP), mucous membrane (cicatricial) pemphigoid (MMP), linear IgA disease (LAD), and chronic bullous dermatosis of childhood (CBDC). The most common clinical features are oral erosions, desquamative gingivitis and conjunctival fibrosis, as well as skin lesions, predominantly in older female population. The heterogeneity of clinical presentation and diversity of target autoantigens have contributed to difficulties in characterizing this condition immunologically. In addition to the clinical presentation and a subepithelial vesicle or bullae on routine histologic analysis, the diagnosis is based on direct and indirect immunofluorescence studies. The nature of the disease is determined by the target antigens in the epithelium and BMZ such as antigen 180 (BP180), antigen 230 (BP230), laminin 5, and beta 4 integrin. Circulating IgG and IgA antibodies bind to different epitopes of BP180. The use of salt-split skin substrate enables differentiation between epidermal and dermal 'binders'. Since the antigen and the antibody titer appear to have direct relationships with the disease severity, and a combination of clinical finding and antibody titer provides valuable prognostic data, these investigations should be carried out routinely. Clinicians should recognize clinical spectrum of SBD, the histopathologic and immunopathologic characteristics, the differential diagnosis, the treatment, and the natural history of the disease. Involvement of oral medicine specialists, dermatologists, ophthalmologists, otolaryngologists and gastroenterologists contribute to early diagnosis and will aid in providing SBD patients with the highest quality of care. [source]

Bullous pemphigoid antigen II (BP180) and its soluble extracellular domains are major autoantigens in mucous membrane pemphigoid: the pathogenic relevance to HLA class II alleles and disease severity

BRITISH JOURNAL OF DERMATOLOGY, Issue 1 2006
N. Oyama
Summary Background, Mucous membrane pemphigoid (MMP), a chronic autoimmune subepithelial blistering disease, is associated with circulating IgG and/or IgA autoantibodies against several basement membrane zone antigens. The heterogeneity of clinical presentation and diversity of target autoantigens have contributed to difficulties in characterizing this condition immunologically. Objectives, To analyse serum autoantibody profile and HLA class II alleles in MMP patients and to correlate this with the clinical presentation of disease. Methods, Well-defined subgroups consisting of 124 patients with MMP were examined for IgG and IgA reactivity with immunoblotting using human epidermal, dermal and placental amnion proteins. The results were further analysed on the basis of detailed clinical (sites of involvement and disease severity) and immunopathological criteria (immunofluorescence study and HLA class II alleles). Results, Immunoblot assay revealed that the majority of MMP patients had IgG (93 of 124, 75%) and/or IgA autoantibodies (63 of 124, 51%) to BP180 (including its soluble ectodomains, 120-kDa LAD-1 and 97-kDa LABD97 antigens). Other antigens targeted predominantly by IgG autoantibodies included: BP230 in 34 (27%), ,4 integrin in 26 (21%), and laminin 5 in three (2%). All the BP230+ sera and 23 (88%) ,4 integrin+ sera also reacted with at least one of the BP180 antigens. Over 85% of patients with reactivity to ,4 integrin had ocular involvement. In most cases of MMP, more severe clinical features were associated with antibody reactivity to multiple basement membrane zone antigens, as well as reactivity to multiple BP180 component antigens. Dual BP180/LAD-1 reactivity with IgG and IgA was associated with a more severe phenotype. In addition, the subset-dependent autoantibody reactivity correlated well with specific HLA class II alleles, DQB1*0301, DRB1*04 and DRB1*11. Conclusions, Our results confirmed that BP180 is a major autoantigen targeted by the sera of patients with MMP. The disease-prevalent HLA class II alleles and humoral autoimmune response against the particular subsets of antigenic epitope(s) within BP180 ectodomain may contribute to the clinicopathological significance and disease severity of MMP. [source]