关键词: Autoantibodies Autoimmunity Dogs Immunoglobulin A Immunoglobulin G Pemphigus foliaceus

Mesh : Dogs Animals Pemphigus / immunology veterinary Desmocollins / immunology Dog Diseases / immunology Immunoglobulin A / immunology blood Autoantibodies / immunology blood Humans HEK293 Cells Immunoglobulin G / immunology blood Fluorescent Antibody Technique, Indirect / veterinary

来  源:   DOI:10.1016/j.vetimm.2024.110773   PDF(Pubmed)

Abstract:
Pemphigus foliaceus (PF) is an autoimmune skin disease of dogs characterized by intraepidermal pustules containing neutrophils and dissociated keratinocytes that develop in association with circulating and tissue-bound IgG autoantibodies. A subset of IgG autoantibodies in canine PF target desmocollin-1 (DSC1), a component of intercellular adhesion complexes within the epidermis. Passive transfer of IgG autoantibodies from canine PF sera to mice was previously shown to induce skin disease in the absence of infiltrating neutrophils. In attempts to identify a mechanism responsible for neutrophil recruitment, past studies evaluated the prevalence of IgA autoantibodies in canine PF sera where they were found in <20% of affected dogs. We re-evaluated the prevalence of anti-DSC1 IgA in canine PF due to concerns regarding the sensitivity of previously used methods. We hypothesized that anti-DSC1 IgA are present in most dogs with PF but have been under-detected due to competition with concurrent anti-DSC1 IgG for binding to their mutual antigenic target. Despite removing approximately 80% of IgG from patient sera using affinity chromatography, we did not detect an increase in anti-DSC1 IgA by performing indirect immunofluorescence on canine DSC1-transfected HEK293T cells. Taken together, our results do not support a role for pathogenic IgA in canine PF.
摘要:
天疱疮(PF)是狗的一种自身免疫性皮肤病,其特征是表皮内脓疱中含有嗜中性粒细胞和解离的角质形成细胞,与循环和组织结合的IgG自身抗体相关。犬PF靶向桥蛋白-1(DSC1)中的IgG自身抗体子集,表皮内细胞间粘附复合物的一种成分。先前已显示,在没有浸润中性粒细胞的情况下,将IgG自身抗体从犬PF血清被动转移到小鼠会诱发皮肤病。为了确定导致中性粒细胞募集的机制,过去的研究评估了IgA自身抗体在犬PF血清中的患病率,其中<20%的受影响的狗中发现了它们。由于担心以前使用的方法的敏感性,我们重新评估了犬PF中抗DSC1IgA的患病率。我们假设抗DSC1IgA存在于大多数患有PF的狗中,但由于与并发抗DSC1IgG竞争结合其相互抗原靶标而未被检测到。尽管使用亲和层析从患者血清中去除大约80%的IgG,通过对犬DSC1转染的HEK293T细胞进行间接免疫荧光,我们未检测到抗DSC1IgA的增加.一起来看,我们的结果不支持致病性IgA在犬PF中的作用.
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