OBJECTIVE: Sjögren's syndrome (SS) is a chronic autoimmune disease characterized by lymphocytic infiltrations of the exocrine glands. Disease progression may lead to uncontrolled clonal proliferation of B lymphocytes and development of lymphoma. This study was undertaken to examine the possible involvement of the cell cycle checkpoint genes p53 and p21 in the pathophysiology of the syndrome. METHODS: Protein expression of p53 and p21 was studied, by immunohistochemistry and Western blot analysis, in minor salivary gland (MSG) biopsy specimens from 7 patients with SS and 5 control subjects. In addition, sequence analysis of the p53 gene was performed on DNA samples obtained from MSG biopsy samples of the same 7 patients with SS and from 4 patients with SS and in situ non-Hodgkin's lymphoma (NHL). RESULTS: The study revealed increased protein expression of p53 and p21 in MSG biopsy specimens from patients as compared with controls, while sequence analysis showed that the p53 gene was of the wild type. Furthermore, sequence analysis of the p53 gene from patients with SS and in situ NHL revealed 2 novel mutations in exon 5 of the p53 gene. These mutations are single-base substitutions and appear to be functional since exon 5 is included in the coding region of the p53 gene. CONCLUSION: This is the first report on wild-type p53 gene activation in SS. Our findings indicate a probable role for the DNA damage response genes in the pathogenesis of this syndrome. The novel mutations of the p53 gene implicate dysregulation of this tumor suppressor gene as a possible mechanism for lymphoma development in SS.
OBJECTIVE: Sjögren's syndrome (SS) is a chronic autoimmune disease characterized by lymphocytic infiltrations of the exocrine glands. Disease progression may lead to uncontrolled clonal proliferation of B lymphocytes and development of lymphoma. This study was undertaken to examine the possible involvement of the cell cycle checkpoint genes p53 and p21 in the pathophysiology of the syndrome. METHODS: Protein expression of p53 and p21 was studied, by immunohistochemistry and Western blot analysis, in minor salivary gland (MSG) biopsy specimens from 7 patients with SS and 5 control subjects. In addition, sequence analysis of the p53 gene was performed on DNA samples obtained from MSG biopsy samples of the same 7 patients with SS and from 4 patients with SS and in situ non-Hodgkin's lymphoma (NHL). RESULTS: The study revealed increased protein expression of p53 and p21 in MSG biopsy specimens from patients as compared with controls, while sequence analysis showed that the p53 gene was of the wild type. Furthermore, sequence analysis of the p53 gene from patients with SS and in situ NHL revealed 2 novel mutations in exon 5 of the p53 gene. These mutations are single-base substitutions and appear to be functional since exon 5 is included in the coding region of the p53 gene. CONCLUSION: This is the first report on wild-type p53 gene activation in SS. Our findings indicate a probable role for the DNA damage response genes in the pathogenesis of this syndrome. The novel mutations of the p53 gene implicate dysregulation of this tumor suppressor gene as a possible mechanism for lymphoma development in SS.
Authors: H Taubert; B Thamm; A Meye; F Bartel; A K Rost; D Heidenreich; V John; J Brandt; M Bache; P Würl; H Schmidt; D Riemann Journal: Clin Exp Immunol Date: 2000-11 Impact factor: 4.330
Authors: Hyunjoo Lee; Shabirul Haque; Jennifer Nieto; Joshua Trott; John K Inman; Steven McCormick; Nicholas Chiorazzi; Patricia K A Mongini Journal: J Immunol Date: 2012-05-18 Impact factor: 5.422
Authors: Adrianos Nezos; Fotini Gravani; Anna Tassidou; Efstathia K Kapsogeorgou; Michael Voulgarelis; Michael Koutsilieris; Mary K Crow; Clio P Mavragani Journal: J Autoimmun Date: 2015-07-14 Impact factor: 7.094
Authors: Shabirul Haque; Xiao Jie Yan; Lisa Rosen; Steven McCormick; Nicholas Chiorazzi; Patricia K A Mongini Journal: FASEB J Date: 2013-10-21 Impact factor: 5.191