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Autoantibodies Specific (autoantibody + specific)

Distribution by Scientific Domains

Medical Sciences	75%

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]

Anti-disialosyl antibodies mediate selective neuronal or Schwann cell injury at mouse neuromuscular junctions

GLIA, Issue 3 2005
Susan K. Halstead
Abstract The human paralytic neuropathy, Miller Fisher syndrome (MFS) is associated with autoantibodies specific for disialosyl epitopes on gangliosides GQ1b, GT1a, and GD3. Since these gangliosides are enriched in synaptic membranes, anti-ganglioside antibodies may target neuromuscular junctions (NMJs), thereby contributing to disease symptoms. We have shown previously that at murine NMJs, anti-disialosyl antibodies induce an ,-latrotoxin-like effect, electrophysiologically characterized by transient massive increase of spontaneous neurotransmitter release followed by block of evoked release, resulting in paralysis of the muscle preparation. Morphologically, motor nerve terminal damage, as well as perisynaptic Schwann cell (pSC) death is observed. The relative contributions of neuronal and pSC injury to the paralytic effect and subsequent repair are unknown. In this study, we have examined the ability of subsets of anti-disialosyl antibodies to discriminate between the neuronal and glial elements of the NMJ and thereby induce either neuronal injury or pSC death. Most antibodies reactive with GD3 induced pSC death, whereas antibody reactivity with GT1a correlated with the extent of nerve terminal injury. Motor nerve terminal injury resulted in massive uncontrolled exocytosis with paralysis. However, pSC ablation induced no acute (within 1 h) electrophysiological or morphological changes to the underlying nerve terminal. These data suggest that at mammalian NMJs, acute pSC injury or ablation has no major deleterious influence on synapse function. Our studies provide evidence for highly selective targeting of mammalian NMJ membranes, based on ganglioside composition, that can be exploited for examining axonal,glial interactions both in disease states and in normal NMJ homeostasis. © 2005 Wiley-Liss, Inc. [source]

Cellular and humoral autoimmunity directed at bile duct epithelia in murine biliary atresia,,

HEPATOLOGY, Issue 5 2006
Cara L. Mack
Biliary atresia is an inflammatory fibrosclerosing lesion of the bile ducts that leads to biliary cirrhosis and is the most frequent indication for liver transplantation in children. The pathogenesis of biliary atresia is not known; one theory is that of a virus-induced, subsequent autoimmune-mediated injury of bile ducts. The aim of this study was to determine whether autoreactive T cells and autoantibodies specific to bile duct epithelia are present in the rotavirus (RRV)- induced murine model of biliary atresia and whether the T cells are sufficient to result in bile duct inflammation. In vitro analyses showed significant increases in IFN-,,producing T cells from RRV-diseased mice in response to bile duct epithelial autoantigen. Adoptive transfer of the T cells from RRV-diseased mice into naïve syngeneic SCID recipients resulted in bile duct,specific inflammation. This induction of bile duct pathology occurred in the absence of detectable virus, indicating a definite response to bile duct autoantigens. Furthermore, periductal immunoglobulin deposits and serum antibodies reactive to bile duct epithelial protein were detected in RRV-diseased mice. In conclusion, both cellular and humoral components of autoimmunity exist in murine biliary atresia, and the progressive bile duct injury is due in part to a bile duct epithelia,specific T cell,mediated immune response. The role of cellular and humoral autoimmunity in human biliary atresia and possible interventional strategies therefore should be the focus of future research. (HEPATOLOGY 2006;44:1231,1239.) [source]

No evidence for association of the TP53 12139 and the BAX,248 polymorphisms with endemic pemphigus foliaceus (fogo selvagem)

INTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 2 2006
K. F. Köhler
Summary Pemphigus foliaceus (PF) is an autoimmune bullous epidermal disease, characterized by autoantibodies specific to the desmosomal protein desmoglein 1 (dsg1) and by acantholysis, the rupture of the cellular junctions among keratinocytes. Known also as fogo selvagem (wild fire) in Brazil, the disease has distinct epidemiological characteristics, being endemic in certain regions of South America. It is a multifactorial (complex) disease, with oligo- or polygenic disease susceptibility. In view of the previously reported evidences of a role for apoptosis dysregulation in pemphigus pathogenesis, we hypothesized that genetic variants of molecules participating in apoptosis may contribute to interindividual variation of susceptibility to PF. The TP53 12139(G,C) and the BAX,248(G,A) single nucleotide polymorphisms (SNP) were analysed in a genetic association study. The allelic, genotypic and allele carrier frequencies for these SNPs did not differ statistically between the patient and the control groups, for both the Euro- and the Afro-Brazilian population strata. The results of this study lead us to conclude that, although the TP53 and BAX alleles analysed differ functionally, this variation does not alter the functionality of the molecules in a way that would interfere with the development of the disease. [source]