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Objective:To investigate the local infiltration of tissue-resident memory CD4 + T (CD4 + T RM) cells in lesions of patients with pemphigus and its clinical implications. Methods:From September 2017 to December 2018, 20 patients with pemphigus and 15 healthy human controls were collected from Department of Dermatology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine. Flow cytometry was performed to determine the proportion of CD4 + T RM cells in skin lesions of pemphigus patients and normal skin of healthy controls. The degree of CD4 + T RM cell infiltration in skin lesions was compared among different body sites of the patients with pemphigus, and the correlation between the proportion of CD4 + T RM cells and the time to disease control was analyzed. Normally distributed data were analyzed by using t test, and non-normally distributed data by using non-parametric test; the Pearson correlation coefficient was used to analyze correlations of the proportion of CD4 + T RM cells with pemphigus disease area index (PDAI) scores and circulating anti-desmoglein (Dsg) antibody titers. Results:Among the 20 patients, there were 16 with pemphigus vulgaris and 4 with pemphigus foliaceus. All the patients had skin involvement, 14 lesional tissue samples were taken from the trunk, and 6 from the limbs. There was no significant difference between the healthy control group and pemphigus group in terms of age, gender or biopsy sites (all P > 0.05) . The proportions of CD3 + T cells (72.75% ± 8.22%) and CD4 + T RM cells (44.05% ± 14.27%) in the skin lesions of patients with pemphigus were significantly higher than those in the skin tissues of the healthy controls (31.33% ± 8.72%, 12.60% ± 5.12%, t = 14.24, 9.10, respectively, both P < 0.001) . Among the patients with pemphigus, the proportion of CD4 + T RM cells was significantly higher in the skin lesions on the trunk (49.57% ± 12.32%) than in those on the limbs (31.17% ± 9.75%, t = 3.23, P < 0.05) . The proportion of CD4 + T RM cells in the skin lesions was positively correlated with the PDAI scores ( r2 = 0.246, P = 0.026) , but not correlated with serum titers of circulating anti-Dsg1 ( r2 = 0.137, P > 0.05) or anti-Dsg3 ( r2 = 0.162, P > 0.05) antibodies in the patients. During the treatment with systemic glucocorticoids, the proportion of CD4 + T RM cells in the skin lesions was significantly higher in the patients whose lesions could not be controlled within 4 weeks than in those whose lesions could be controlled within 4 weeks ( t = 3.22, P < 0.05) . Conclusion:The proportion of CD4 + T RM cells markedly increased in the skin lesions of patients with pemphigus, which may be related to the severity of the disease and response to treatment.
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Objective To evaluate the specific antibody-producing capacity of locally infiltrating B lymphocytes in lesions of patients with pemphigus vulgaris (PV).Methods Totally,35 patients with PV and 22 healthy controls were enrolled into this study.Skin tissues were resected from blisters or erosions of the patients with PV,and from normal skin of healthy controls.Then,mononuclear cells were isolated from these skin tissues.Flow cytometry was performed to determine the percentages of lymphocytes,CD 19+ B lymphocytes,and desmoglein (Dsg)1-and Dsg3-specific CD19+ B lymphocytes.B lymphocytes isolated from the lesional skin of patients with PV were cultured in vitro.Enzyme-linked immunosorbent assay (ELISA) was conducted to determine titers of anti-Dsg1 and anti-Dsg3 antibodies in the cell culture supernatant.Receiver operating characteristic (ROC) curve analysis was conducted to calculate positive rates of anti-Dsg1 and anti-Dsg3 antibodies.Results The percentages of lymphocytes (17.95％ ± 3.85％) and CD19+ B lymphocytes (4.27％ ± 1.13％) were significantly higher in the lesional skin of PV patients than in the normal skin of healthy controls (7.83％ ± 1.29％,0.61％ ± 0.31％ respectively;t =2.49,U =13.00 respectively,both P ＜ 0.05).Among the CD19+ B lymphocytes in the lesional skin of PV patients,the percentage of CD19qgG+ B cells was (38.33 ± 5.56)％,and percentages of Dsg1-and Dsg3-specific CD19+ B lymphocytes were 12.87％ ± 1.267％ and 10.42％ ± 1.243％ respectively.After the in vitro culture for 6 days,the titers of anti-Dsg1 and anti-Dsg3 antibodies in the cell culture supematant were (4.89 ± 1.56) U/ml and (35.45 ± 13.03) U/ml respectively,with their positive rates being 85％ (17/20)and 95％ (19/20) respectively.Conclusion There are Dsg1-and Dsg3-specific B lymphocytes aggregating in the lesional skin of patients with PV,which can produce anti-Dsg1 and anti-Dsg3 antibodies after in vitro culture.
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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.
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Objective To summarize clinical and histopathological features of trauma-triggered autoimmune bullous skin diseases,and to explore its possible pathogenesis.Methods Clinical manifestations,histopathological features and treatment of 3 cases of trauma-triggered pemphigus or pemphigoid were analyzed,and summarized according to related domestic and overseas literature.Results Of the 3 cases,1 was a female aged 62 years,and 2 were males aged 60 and 71 years respectively.They all had a history of skin trauma or surgery before the onset of the diseases,and time intervals from trauma to diseases were 5,5 weeks and 3 days respectively.The 3 cases were diagnosed as bullous pemphigoid (anti -BP180 antibody 109 U/ml,anti-BP230 antibody negative),pemphigus vulgaris (anti-Dsg1 antibody 68.8 U/ml,anti-Dsg3 antibody 219 U/ml) and pemphigus foliaceus (anti-Dsg1 antibody 143 U/ml,anti-Dsg3 antibody negative) respectively.Their lesions were relieved dramatically after oral and (or) topical glucocorticoid treatment.Conclusions Trauma may be a triggering factor for autoimmune bullous skin diseases.For patients with post-traumatic poor wound healing or skin erythema,blisters and erosion,which can hardly be attributed to trauma or surgery itself,autoimmune bullous skin diseases should be considered,and histopathological or immunopathological examinations should be performed timely.
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Objective To assess the effectiveness and safety of propranolol in infantile hemangiomas by comparing with prednisone.Methods A systematic literature search of PubMed,Embase,Cochrane,Ovid,Google Scholar and CNKI,VIP,Wanfang database was conducted to identify studies about the treatment of propranolol in children with hemangiomas.We chose randomized controlled trials and clinical controlled trials.We selected literatures by certain standards.Results Eight papers including 9 studies were identified by the strategy mentioned above.These 8 literatures met our inclusion criteria after review by two independent reviewers.The studies comprised 407 patients.Six of the control group were oral prednisone,and there was no statistic heterogeneity (P =0.09,I2 =0％).The fixed model was used to do the statistic analysis.The outcome showed the effective rate of propranolol was higher than that of prednisone,with statistically significant difference (OR=7.56,95％ CI:3.18-17.98).Three of the control group included observation or oral placebo,without statistic heterogeneity (P=0.48,I2=0％) either.The outcome showed the effective rate of propranolol on hemangioma was higher than that of the control group (OR=23.15,95％CI:7.15-74.94).Of all the eight researches,five reported adverse effects,with statistic heterogeneity (P=0.0003,I2 =81 ％).In addition,the adverse rate of propranolol was lower than that of prednisone,with statistically significant difference (OR=0.12,95％ CI:0.02-0.75).Conclusions The results of this meta-analysis show that oral propranolol could obviously decrease the volume and improve the color of infantile hemangiomas.And propranolol is a significantly more effective for IH than steroids.The incidence of adverse effects of propranolol is also lower than that of prednisone.As a result,propranolol should be recommended as the first choice therapy for infantile hemangioma.
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<p><b>OBJECTIVE</b>To investigate the significance of beta-adrenergic receptor 2 (beta2-AR) and vascular endothelial growth factor-2 (VEGFR-2) in the occurrence and development of infantile hemangioma through detecting the expression of beta2-AR and VEGFR-2 in the different stages of infantile hemangiomas.</p><p><b>METHODS</b>According to the Mulliken's classification standard, we classified the specimens as proliferating group (32 cases), involuting group (17 cases) and involuted group (11 cases). Normal skin tissue surrounding the hemangioma from 7 cases were chosen as control group. The expression of beta2-AR and VEGFR-2 was detected by immunohistochemical technique in proliferating hemangioma, involuting hemangioma, involuted hemangioma. The mean optical density was measured by image analysis system (Image Pro Plus 6.0) and SPSS 16.0 software was applied for statistical analysis.</p><p><b>RESULTS</b>The expression of beta2-AR and VEGFR-2 was strongly positive in proliferating hemangioma, while positive in involuting hemangioma and weakly positive in the involuted stage. The mean optical density of each phase was 0.064 751 2 +/- 0.012 747, 0.031 6017 +/- 0.006 848,0.011 869 8 +/- 0.039 349 for beta2-AR, and 0.068 940 9 +/- 0.029 274, 0.028 445 5 +/- 0.006 396, 0.011 184 1 +/- 0.004 198 for VEGFR-2. The differences between different stages had a statistically significance (P < 0.05). Correlation analysis on the mean optical density between beta2-AR and VEGFR-2 had a statistically significance (P < 0. 05).</p><p><b>CONCLUSIONS</b>Beta2-AR and VEGFR-2 may be involved in the occurrence and development of infantile hemangioma.</p>