Sami N, Bhol K C, Beutner E H, Plunkett R W, Leiferman K M, Foster C S, Ahmed A R
Department of Oral Medicine, Harvard School of Dental Medicine, Boston, Massachusetts 02115, USA.
Clin Immunol. 2001 Aug;100(2):219-27. doi: 10.1006/clim.2001.5065.
There are several reports in the literature describing the coexistence of features of pemphigus vulgaris and pemphigoid in the same patient. We describe 15 patients with clinical, histological, and immunopathological features of mucous membrane (cicatricial) pemphigoid at the time of initial diagnosis. All 15 patients failed to respond clinically to conventional systemic agents over a mean period of 7.2 years. Hence, IVIg therapy was used. Prior to initiating IVIg therapy, features of mucous membrane pemphigoid and pemphigus vulgaris were demonstrated by various serological tests. Different assays were performed to identify molecular characteristics of these two autoantibodies. Twenty-five healthy normal individuals, 22 patients with mucous membrane pemphigoid, 17 patients with pemphigus vulgaris, and 12 patients with pemphigus foliaceus served as controls for comparison of serological studies. On indirect immunofluorescence, using monkey esophagous as substrate, sera of all 15 patients had demonstrable levels of anti-intercellular cement substance (ICS) or anti-keratinocyte cell surface antibody. Sera of 14 patients on salt split skin bound to the epidermal side of the split, which was consistent with mucous membrane pemphigoid. Sera of all 15 patients demonstrated binding to a 205-kDa protein (human B4 integrin) and a 130-kDa protein (desmoglein 3) on immunoblot. In a sample of sera from each of the 6 patients with mucous membrane pemphigoid and pemphigus vulgaris, the anti-ICS antibody was of the IgG4 subclass. The IgG4 subclass is a characteristic feature associated with pathogenic autoantibodies in pemphigus vulgaris. Hence, in such patients, a dual diagnosis should be considered and confirmed by various serological assays. It is possible that the presence of two pathogenic autoantibodies in these patients could have contributed to the lack of response to conventional immunosuppressive therapy.
文献中有几篇报道描述了寻常型天疱疮和类天疱疮的特征在同一患者中共存的情况。我们描述了15例初诊时具有黏膜（瘢痕性）类天疱疮临床、组织学和免疫病理学特征的患者。所有15例患者在平均7.2年的时间里对传统全身用药均无临床反应。因此，采用了静脉注射免疫球蛋白（IVIg）治疗。在开始IVIg治疗之前，通过各种血清学检测证实了黏膜类天疱疮和寻常型天疱疮的特征。进行了不同的检测以鉴定这两种自身抗体的分子特征。25名健康正常个体、22例黏膜类天疱疮患者、17例寻常型天疱疮患者和12例落叶型天疱疮患者作为对照用于血清学研究的比较。在间接免疫荧光检测中，以猴食管为底物，所有15例患者的血清均有可检测水平的抗细胞间黏附物质（ICS）或抗角质形成细胞表面抗体。14例患者的血清在盐裂皮肤上与裂隙的表皮侧结合，这与黏膜类天疱疮一致。所有15例患者的血清在免疫印迹上均显示与一种205-kDa蛋白（人B4整合素）和一种130-kDa蛋白（桥粒芯糖蛋白3）结合。在6例黏膜类天疱疮和寻常型天疱疮患者的每份血清样本中，抗ICS抗体为IgG4亚类。IgG4亚类是寻常型天疱疮中与致病性自身抗体相关的特征性表现。因此，对于此类患者，应考虑双重诊断并通过各种血清学检测加以证实。这些患者中存在两种致病性自身抗体可能导致了对传统免疫抑制治疗无反应。
