天疱疮患者皮损局部异位淋巴结构的病理学特征

Pathological features of ectopic lymphoid structure in skin lesions of patients with pemphigus

目的 探讨天疱疮患者皮损处浸润淋巴细胞病理学特征及其与外周血抗桥粒黏蛋白（Dsg）1/Dsg3抗体滴度的相关性。方法 对2014—2016年上海交通大学医学院附属瑞金医院皮肤科93例寻常型和落叶型天疱疮患者的组织病理片进行分析。计算每例 × 50镜下淋巴细胞总数，定义为淋巴细胞密集程度指数。采用酶联免疫吸附试验（ELISA）测定天疱疮患者血清中抗Dsg1/Dsg3抗体滴度。统计淋巴细胞密集程度指数与抗体滴度间相关性。对其中8例寻常型和8例落叶型天疱疮患者的皮损样本进行免疫组化染色，分析CD3^＋ T细胞、CD20^＋ B细胞、CD138^＋ 浆细胞的分布。结果 在93例病理切片中，Grade1、Grade2、Grade3淋巴细胞聚集出现概率分别为100.00%、68.09%、10.64%，寻常型（56例）和落叶型天疱疮（37例）比较，Grade1-3淋巴细胞聚集出现概率差异无统计学意义。淋巴细胞的密集程度在寻常型和落叶型天疱疮患者比较，差异无统计学意义，与天疱疮患者血清中特异性抗Dsg1和抗Dsg3 的抗体滴度无相关性。在16例天疱疮病例中，全部有CD3^＋ T细胞出现，15例有CD20^＋ B细胞，12例有CD138^＋ 浆细胞存在。16例切片中，Grade1-3淋巴细胞聚集区域中均含有大量的CD3^＋ T细胞，而含有CD20^＋ B细胞的淋巴细胞聚集占总数的52.80% ± 5.78%，含有CD138^＋ 浆细胞的淋巴细胞聚集占总数的34.59% ± 7.42%。CD3^＋ T细胞、CD20^＋ B细胞、CD138^＋ 浆细胞在寻常型（8例）和落叶型天疱疮（8例）分布差异无统计学意义。结论 天疱疮患者皮损处普遍出现不同程度的淋巴细胞浸润，可能形成异位淋巴结构，参与皮损的形成和加重。

Objective To investigate pathological features of infiltrating lymphocytes in skin lesions of patients with pemphigus, and to analyze their correlation with titers of anti-desmoglein （Dsg）1 and anti-Dsg3 antibodies in peripheral blood. Methods A retrospective pathological analysis was performed in 93 patients with pemphigus vulgaris or pemphigus foliaceus, who visited the Department of Dermatology of Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine between 2014 and 2016. For each HE-stained section, the total number of lymphocytes per ×50 microscopic field was counted, and defined as lymphocyte density index. Enzyme-linked immunosorbent assay （ELISA） was conducted to determine the serum titers of anti- Dsg1 and anti-Dsg3 antibodies in the patients with pemphigus. The correlations between the lymphocyte density index and titers of anti- Dsg1 and anti-Dsg3 antibodies were analyzed. Immunohistochemical staining was performed in lesional skin samples from 8 patients with pemphigus vulgaris and 8 patients with pemphigus foliaceus, so as to analyze the distribution of CD3^＋ T cells, CD20^＋ B cells and CD138^＋ plasma cells. Results Of the 93 pathological sections, 93 （100.00%） showed Grade1 lymphocyte aggregates, 64 （68.09%） showed Grade 2 lymphocyte aggregates, and 10 （10.64%） showed Grade 3 lymphocyte aggregates, and the 56 cases of pemphigus vulgaris and 37 of pemphigus foliaceus showed the similar proportion of grade 1, 2 and 3 lymphocyte aggregates. There was also no significant difference in the lymphocyte density index between patients with pemphigus vulgaris and pemphigus foliaceus （P 〉 0.05）, and the lymphocyte density index was uncorrelated with the serum titers of anti-Dsg1 and anti-Dsg3 antibodies in patients with pemphigus. Of the 16 cases of pemphigus, CD3^＋ T cells were found in all cases, CD20^＋ B cells in 15, and CD138^＋ plasma cells in 12. Of 16 sections, all showed a large amount of CD3^＋ T cells in Grade 1 - 3 lymphocyte aggregates, while lymphocyte aggregates containing CD20^＋ B cells and CD138^＋ plasma cells were found in 52.80% ± 5.78% and 34.59% ± 7.42% of sections respectively. No significant differences in the distribution of CD3^＋ T cells, CD20^＋ B cells, CD138^＋ plasma cells were found between the 8 cases of pemphigus vulgaris and 8 cases of pemphigus foliaceus. Conclusion Different degrees of lymphocyte infiltration generally exist in skin lesions of patients with pemphigus, which may form ectopic lymphoid structures and contribute to the development and aggravation of pemphigus skin lesions.