Sami N, Bhol K C, Ahmed A R
Center for Blistering Diseases, Department of Medicine, New England Baptist Hospital, Boston, MA, USA.
Clin Exp Immunol. 2002 Sep;129(3):533-40. doi: 10.1046/j.1365-2249.2002.01942.x.
Oral pemphigoid (OP) is a chronic autoimmune disease, involving the oral cavity, characterized by a homogenous linear deposition of immunoglobulins, complement, or both along the basement membrane zone (BMZ) and a subepithelial blister formation. The alpha6/beta4 heterodimer is an integrin family of adhesion receptors, which mediates basal cell to matrix interactions. Recent evidence suggests a pathophysiologic role for antibodies against human alpha6 integrin in blister formation in OP, in organ culture studies. Fifty percent of OP patients have been reported to experience disease progression to involve other mucosal tissues, including the eye and larynx. To prevent this extension of disease, systemic therapy with systemic corticosteroids, dapsone, and immunosuppressive agents has been recommended. The use of intravenous immunoglobulin (IVIg) in the treatment of pemphigoid has been recently described. In this study, we present the use of IVIg, in a group of seven patients, with severe OP, in whom systemic conventional treatment was contraindicated. To determine the influence of treatment on antibodies to human alpha6 integrin in OP, seven patients with OP treated with IVIg therapy and a comparable control group of seven patients with OP, treated with conventional therapy, were evaluated at monthly intervals, for a 12 consecutive month treatment period. An effective clinical response was observed in all seven patients treated with IVIg therapy, after a mean treatment period of 4.5 months. IVIg therapy induced a prolonged and sustained clinical remission in all seven patients after a mean treatment period of 26.9 months. A statistically significant difference was observed in the quality of life pre- and post-IVIg therapy (P < 0.001). Both the study and the control groups had a very similar initial serological response to treatment. A statistically significant reduction in the antibody titres was observed after four months of treatment, in both groups (P = 0.015). Thereafter, patients treated with IVIg therapy had a faster rate of decline in the antibody titres, and the difference in the rate of decline between the study and control groups became statistically significant after six months of treatment (P = 0.03). The use of IVIg therapy resulted in reduction of antialpha6 antibody titres and in inducing and maintaining both a sustained, clinical and serological remission.
口腔类天疱疮（OP）是一种慢性自身免疫性疾病，累及口腔，其特征为免疫球蛋白、补体或两者沿基底膜带（BMZ）呈均匀线性沉积以及上皮下疱形成。α6/β4异二聚体是一种整合素家族的黏附受体，介导基底细胞与基质的相互作用。近期证据表明，在器官培养研究中，抗人α6整合素抗体在OP的疱形成中具有病理生理作用。据报道，50%的OP患者会出现疾病进展，累及包括眼和喉在内的其他黏膜组织。为防止疾病扩展，已推荐使用全身用皮质类固醇、氨苯砜和免疫抑制剂进行全身治疗。最近有人描述了静脉注射免疫球蛋白（IVIg）在类天疱疮治疗中的应用。在本研究中，我们报告了IVIg在一组7例重度OP患者中的应用，这些患者因禁忌而无法接受全身常规治疗。为确定治疗对OP患者抗人α6整合素抗体的影响，对7例接受IVIg治疗的OP患者和7例接受常规治疗的OP患者组成的可比对照组，在连续12个月的治疗期内每月进行评估。在平均治疗期4.5个月后，所有7例接受IVIg治疗的患者均观察到有效的临床反应。在平均治疗期26.9个月后，IVIg治疗使所有7例患者实现了长期且持续的临床缓解。IVIg治疗前后的生活质量存在统计学显著差异（P < 0.001）。研究组和对照组对治疗的初始血清学反应非常相似。两组在治疗4个月后抗体滴度均出现统计学显著降低（P = 0.015）。此后，接受IVIg治疗的患者抗体滴度下降速度更快，治疗6个月后，研究组和对照组之间的下降速度差异具有统计学显著性（P = 0.03）。使用IVIg治疗可降低抗α6抗体滴度，并诱导和维持持续的临床和血清学缓解。
