Objective To identify genes that may participate in the pathophysiology of Sjögren's syndrome (SS), the technique of differential display was applied to labial minor salivary gland (MSG) biopsy samples. Methods Total RNA was isolated from MSG biopsy samples from a woman with primary SS and a control subject, and the differential display protocol with 8 different random oligonucleotide primers was performed. One particular differentially expressed fragment showed 98% homology with the cysteine‐rich secretory protein 3 (CRISP‐3) gene. The result was verified by reverse transcription‐polymerase chain reaction (RT‐PCR) with messenger RNA (mRNA) samples from MSG biopsy tissues obtained from 4 women with primary SS. A CRISP‐3 RNA probe was synthesized for in situ hybridization of 7 MSG biopsy samples from patients with primary SS. In an attempt to interpret the expression of CRISP‐3, normal peripheral blood lymphocytes (PBLs) were activated in vitro at different time points and assayed for CRISP‐3 expression. Finally, B cells were transfected with the coding region of CRISP‐3 and monitored for the up‐regulation of different B cell activation markers. Results The CRISP‐3 gene was detected by RT‐PCR in all SS patients tested. Mainly the mononuclear cells infiltrating the MSGs of patients expressed CRISP‐3 mRNA. In addition, CRISP‐3 was detected by RT‐PCR between 30 minutes and 6 hours in phorbol myristate acetate‐activated normal PBLs, while staurosporine inhibited this expression. CRISP‐3‐transfected B cells exhibited an up‐regulation in CD25 surface expression. Conclusion The CRISP‐3 gene is identified as a novel early response gene that may participate in the pathophysiology of the autoimmune lesions of SS.

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The protein tyrosine phosphatase CD45 is a highly expressed glycoprotein present on all nucleated cells of hematopoietic origin. To date, all the functions attributed to CD45 are inherently coupled to its phosphatase activity. For instance, the regulation of lymphocyte antigen receptor signaling is mediated through the dephosphorylation, and hence activation, of Src-family kinases by CD45. Moreover, signaling via cytokine receptors is negatively modulated by CD45 by dephosphorylation of Janus kinase family members. Recently, another function for CD45, unrelated to regulation of surface receptor signaling, has been unraveled. Specific engagement of CD45 by monoclonal antibodies at the surface of lymphocytes induced their death, through an alternative caspase-independent pathway. In striking contrast to all other previously reported functions for CD45, its phosphatase activity is completely dispensable for the induction of cell death. This article reviews the current knowledge on the death pathway triggered by CD45 ligation on lymphocytes. In an attempt to better elucidate the mechanism of cell death induction through CD45, we also provide original data regarding the susceptibility of various subsets of immature and mature T and B cells to death induced by CD45 engagement. The physiological significance and therapeutic potential of CD45-induced death are also discussed.