Objective, Sjogren's syndrome (SS) is a chronic autoimmune disease characte
rized by lymphocytic infiltrations of the exocrine glands. Disease progress
ion may lead to uncontrolled clonal proliferation of B lymphocytes and deve
lopment of lymphoma. This study was undertaken to examine the possible invo
lvement of the cell cycle checkpoint genes p53 and p21 in the pathophysiolo
gy of the syndrome.
Methods. Protein expression of p53 and p21 was studied, by immunohistochemi
stry and Western blot analysis, in minor salivary gland (MSG) biopsy specim
ens from 7 patients with SS and 5 control subjects. In addition, sequence a
nalysis of the p53 gene was performed on DNA samples obtained from MSG biop
sy samples of the same 7 patients with SS and from 4 patients with SS and i
n 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 sequenc
e analysis showed that the p53 gene was of the wild type, Furthermore, sequ
ence analysis of the p53 gene from patients with SS and in situ NHL reveale
d 2 novel mutations in exon 5 of the p53 gene. These mutations are single-b
ase substitutions and appear to be functional since exon 5 is included in t
he 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 i
n the pathogenesis of this syndrome. The novel mutations of the p53 gene im
plicate dysregulation of this tumor suppressor gene as a possible mechanism
for lymphoma development in SS.