Moll R, Bahn H, Bayerl C, Moll I
Institut für Pathologie, Martin-Luther-Universität Halle-Wittenberg Halle, Saale.
Pathologe. 1996 Jul;17(4):254-61. doi: 10.1007/s002920050163.
Cell-cell and cell-matrix adhesion molecules as well as extracellular matrix components are target structures of antibody-mediated autoimmunity that have recently been well characterized at the molecular biological level. Pathogenic autoantibodies against these molecules are causally related to disturbances of cell and tissue adhesion that become apparent as various (muco-)cutaneous blistering diseases. Desmosomal cadherins (desmogleins and desmocollins) mediate epidermal intercellular adhesion. Among these, desmoglein 1 and desmoglein 3 are the autoantigens of pemphigus foliaceus and pemphigus vulgaris, respectively, exhibiting intraepidermal blistering. The pathogenic relevance of autoantibodies against desmocollins. (IgA pemphigus) and desmoplakins (paraneoplastic pemphigus) still remains unclear. Hemidesmosomes contain the plaque protein BPAG1 and the partly collagen-like transmembrane protein BPAG2, representing the autoantigens of bullous pemphigoid and pemphigoid gestationis with subepidermal blistering. A certain subtype of cicatricial (benign mucous membrane) pemphigoid is characterized by autoantibodies against laminin 5 present in the subhemidesmosomal anchoring filaments, while epidermolysis bullosa acquisita and bullous SLE exhibit autoantibodies against collagen type VII constituting the anchoring fibrils. In addition, autoantibodies against a particular collagen type IV chain of the glomerular basement membrane are responsible for the manifestation of Goodpasture's syndrome. These recent molecular biological findings might be the basis for the development of novel therapeutic strategies.
细胞间和细胞与基质黏附分子以及细胞外基质成分是抗体介导的自身免疫的靶结构，最近在分子生物学水平上已得到充分表征。针对这些分子的致病性自身抗体与细胞和组织黏附紊乱存在因果关系，这些紊乱在各种（黏液性）皮肤水疱病中表现明显。桥粒钙黏蛋白（桥粒芯糖蛋白和桥粒胶蛋白）介导表皮细胞间黏附。其中，桥粒芯糖蛋白1和桥粒芯糖蛋白3分别是落叶型天疱疮和寻常型天疱疮的自身抗原，表现为表皮内水疱形成。针对桥粒胶蛋白（IgA天疱疮）和桥粒斑蛋白（副肿瘤性天疱疮）的自身抗体的致病相关性仍不清楚。半桥粒含有斑块蛋白BPAG1和部分胶原样跨膜蛋白BPAG2，它们是大疱性类天疱疮和妊娠类天疱疮的自身抗原，表现为表皮下水疱形成。瘢痕性（良性黏膜）类天疱疮的某一亚型的特征是存在针对半桥粒锚定细丝中层粘连蛋白5的自身抗体，而获得性大疱性表皮松解症和大疱性系统性红斑狼疮则表现出针对构成锚定原纤维的VII型胶原的自身抗体。此外，针对肾小球基底膜特定IV型胶原链的自身抗体是古德帕斯彻综合征表现的原因。这些最新的分子生物学发现可能是开发新型治疗策略的基础。
