Noncomplement fixing, IgG(4) autoantibodies predominate in patients with anti-epiligrin cicatricial pemphigoid
Noncomplement fixing, IgG(4) autoantibodies predominate in patients with anti-epiligrin cicatricial pemphigoid
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DOI：
10.1111/1523-1747.ep12337073
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发表时间：
1997-10-01
影响因子：
6.5
通讯作者：
Yancey, KB
中科院分区：
文献类型：
--
作者：
Hsu, R;Lazarova, Z;Yancey, KB
本研究对12例抗瘢痕性类天疱疮患者抗层粘连蛋白-5抗体的特异性、免疫球蛋白G亚类和补体固定能力进行了研究。所有患者的循环免疫球蛋白与1M氯化钠裂解皮肤真皮侧结合，免疫沉淀层粘连蛋白-5由生物合成放射性标记的人角质形成细胞产生，并(在12例中有10例)免疫印迹层粘连蛋白-α3亚单位。用HP系列亚类特异性单抗对这些患者循环中抗层粘连蛋白-5自身抗体的半定量间接免疫荧光显微镜分析表明：(I)在11份血清中有7份以Ig G(4)为主；(Ii)在少数血清中，Ig G(1)和Ig G(2)水平相当低；(3)在任何患者中均无特异性Ig G(3)抗层粘连蛋白-5自身抗体。在纯化的人层粘连蛋白5的酶联免疫吸附试验研究中，发现抗层粘连蛋白-5自身抗体的免疫球蛋白(4)-显性图谱相同。对3例患者的6例皮肤活检直接免疫荧光显微镜观察发现，在原位的表皮基底膜中，免疫球蛋白G(4)也是主要的免疫球蛋白亚类。与这些发现一致的是，11例抗层粘连蛋白-5自身抗体的患者中有11例的血清在体外不能对表皮基底膜产生C3。这些免疫化学研究表明，补体激活在这种疾病的病理生理学中不起主要作用，这些患者的真皮下水泡可能通过抗层粘连蛋白-5抗体本身的直接作用而发展。
This study characterized the specific reactivity, IgG subclass, and complement fixing ability of anti-laminin-5 IgG from 12 patients with anti-epiligrin cicatricial pemphigoid. Circulating IgG from all patients bound the dermal side of 1 M NaCl split skin, immunoprecipitated laminin-5 produced by biosynthetically radiolabeled human keratinocytes, and (in 10 of 12 cases) immunoblotted the laminin-alpha 3 subunit. Analysis of the distribution of IgG subclasses in these patients' circulating anti-laminin-5 autoantibodies by semiquantitative indirect immunofluorescence microscopy using the HP series of subclass-specific monoclonal antibodies revealed: (i) IgG(4) predominant autoantibodies in seven of 11 sera; (ii) IgG(1) and IgG(2) at substantially lower levels in a smaller number of sera; and (iii) no specific IgG(3) anti-laminin-5 autoantibodies in any patients. The same IgG(4)-dominant profile of anti-laminin-5 autoantibodies was found in enzyme-linked immunosorbent assay studies of purified human laminin 5. Direct immunofluorescence microscopy of six skin biopsies from three patients found that IgG(4) was also the predominant subclass of IgG in epidermal basement membranes in situ. Consistent with these findings, sera from 11 of 11 patients with anti-laminin-5 IgG autoantibodies did not fur C3 to epidermal basement membranes in vitro. These immunochemical studies suggest that complement activation does not play a major role in the pathophysiology of this disease and that subepidermal blisters in these patients may develop via a direct effect of anti-laminin-5 IgG itself.