The Expression Of Glucocorticoid Receptor In The Lesion Of Pemphigus And Its Significances

Objective: In the sera of most Pemphigus patients have circulating anti-desmoglein (Dsg) 3 immunoglobulin G (IgG) autoantibodies, direct immunofluorescence (DIF) reveals IgG deposition on keratinocyte cell surfaces in the epidermis of all cases, usually associated with C3 deposition, suggesting the disease is an autoimmune disease. But Familial Benign Chronic Pemphigus (FBCP) or Hailey-Hailey disease (HHD) is an autosomal dominant disease and is resulted from malfunction of the Ca2+-dependent ATPase. Glucocorticoid (GC) is the key factor of the hypothalamus-hypophysis-adrenal axis and has very important regulation action on some physiological processes, such as growth, endocrine and metabolism. GC has powerful immunosuppression function and it is extensively used to treat many autoimmune diseases, including Pemphigus.GC takes its effect by binding with the glucocorticoid receptor (GR) in the cytoplasm of the cells, whose aggregation on skin tissue affect local inflammation. On the first aspect, GC can prevent the addiment from activation, may affect the enlisting of neutrophil, lymphocyte and eosinophilic granulocyte; can decrease the production of proteolytic enzyme and many kinds of cytokines. In another aspect, GC can restrain the production of pathogenicity antibody by its immunosuppressive action. It has been found that the different clinical patients of bullous diseases have different response to GC and the part of patients are unsensitive to the GC therapy, which brings about the challenge in the clinical treatment of these diseases. However, the molecular mechanism unsensitive to GC is not fully understood.Method: Forty patients with Pemphigus and thirty patients with HHD were diagnosed clinically and histopathologically. All of them were collected from the dermatological department of the Fourth Affiliated Hospital of Hebei Medical University and the dermatological department of Affiliated Hospital of Hebei Engineer University from November 1999 to September 2006. Thirty healthy skin specimens were taken as controls. All of them had no systemic diseases. They had no statistical difference in gender and age between controls and the patients. All the specimens were cut to 3μm serial section for roution HE staining and immunohistochemistry SP staining respectively.All data were analyzed by SPSS11.5. Kruskal-Wallis H, Mann-Whitney U rank sum test and Spearman rank correlation analysis, statistically processed the results of immunohistochemistry. P<0.05 was significant.Results: 1 The expression of GRα: The GRαwas distributed in the all stratums of epidermis with more quantity of cells in all the patients with pemphigus. 26 of 40 patients with pemphigus were strongly positive, 12 positive, only 2 weakly positive. In the controls, the GRαexpression was mainly stained in the cells of stratum basale with much quantity of cells. 18 of them were positive, 12 weakly positive. In the HHD patients, the GRαwas expressed in the cells of stratum basale with small quantity of cells. 8 of 30 patients with HHD were negative, 22 weakly positive. The results showed there were statistically significant differences in among of the three groups (P<0.05).2 The expression of GRβ: The GRβwas manily expressed in the cells of stratum basale with small quantity of cells in the patients with pemphigus. 15 of 40 patients with pemphigus were negative, 23 weakly positive, only 2 positive. In the controls, it was manily expressed in the cells of stratum basale with small quantity of cells. 16 of the 30 controls were negative, 14 weakly positive. But in the patients with HHD, it was overexpressed in the cells of stratum basale with much quantity of cells. 14 of them were positive, 6 weakly positive, 10 negative. The results showed there's not statistically significant difference in the GRβexpression between pemphigus group and controls (P>0.05), however, GRβin the HHD group was overexpressed compared with the other two groups and there's statistically significant difference (P<0.05).3 The expression of GRαhadn't statistically significant difference between patients with pemphigus vulgaris (PV) and pemphigus erythematosus (PE) (P>0.05), but the expression of GRβin PV patients was higher than in PE patients (P<0.05), showing statistically significant difference. 4 There weren't statistically significant difference in the expression of GRαand GRβbetween the male and female patients with pemphigus (P>0.05).5 There wasn't correlation between the expression of GRαand GRβin Pemphigus (P>0.05) and there wasn't correlation between the expression of GRαand GRβin HHD (P>0.05).6 The expression of GRαand GRβis manily distributed in the epidermis; the little expression of GRαand GRβis distributed in the dermis.Conclusions: 1 The expression of GRαin Pemphigus is higher than in controls, the expression of GRαin controls is higher than in HHD, showing that the better therapeutic effect of GC is correlated with the more quantity of GRαexpression.2 The expression of GRβin HHD is higher than in another two groups, suggesting that the low therapeutic effect of GC is correlated with the more quantity of GRβexpression.3 The expression GRβis perhaps related with the type of disease, which may produces more opposite effectiveness in the treatment of PV patients.4 The levels of GRαand GRβexpression in Pemphigus is unrelated with the gender.5 There isn't correlation between the expression of GRαand GRβin the pemphigus patients. The results are similar to that in the HHD patients.6 The expression of GRαand GRβis manily distributed in the epidermis; the little expression of GRαand GRβis distributed in the dermis, showing that the epidermis is one of important target parts of the GC.