%0 Journal Article
%T Posttranslational Protein Modification in the Salivary Glands of Sj£¿gren¡¯s Syndrome Patients
%A Rafael Herrera-Esparza
%A Mayra Rodr¨ªguez-Rodr¨ªguez
%A Mar¨ªa Elena P¨¦rez-P¨¦rez
%A Martha Adriana Badillo-Soto
%A Felipe Torres-del-Muro
%A Juan Jos¨¦ Bollain-y-Goytia
%A Deyanira Pacheco-Tovar
%A Esperanza Avalos-D¨ªaz
%J Autoimmune Diseases
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/548064
%X The present study investigated posttranslational reactions in the salivary glands of patients with Sj£¿gren¡¯s syndrome. We analysed the biopsies of primary Sj£¿gren¡¯s patients using immunohistochemistry and a tag-purified anticyclic citrullinated protein (CCP) antibody to detect citrullinated peptides, and the presence of peptidylarginine deiminase 2 (PAD2) was assessed simultaneously. The present work demonstrated the weak presence of the PAD2 enzyme in some normal salivary glands, although PAD2 expression was increased considerably in Sj£¿gren¡¯s patients. The presence of citrullinated proteins was also detected in the salivary tissues of Sj£¿gren¡¯s patients, which strongly supports the in situ posttranslational modification of proteins in this setting. Furthermore, the mutual expression of CCP and PAD2 suggests that this posttranslational modification is enzyme dependent. In conclusion, patients with Sj£¿gren¡¯s syndrome expressed the catalytic machinery to produce posttranslational reactions that may result in autoantigen triggering. 1. Introduction Sj£¿gren¡¯s syndrome is an autoimmune epithelitis that primarily affects the salivary and lachrymal glands and results clinically in Sicca syndrome, which is characterised by xerostomia, xerophthalmia, and keratoconjunctivitis [1]. Citrulline is an ¦Á-amino acid that can be isolated from watermelon [2]. In addition, it is an intermediate compound of the urea cycle and is synthesised in the liver by the conversion of ornithine to arginine during urea formation [3]. Citrulline exists in two forms: free citrulline, which is a product of the NOS enzyme family, and citrulline that results from the posttranslational modification of certain proteins at arginine residues, which is catalysed by peptidylarginine deiminases (PADs). This family of enzymes deiminates proteins at arginine residues to yield citrulline residues, and in this manner, protein citrullination is NOS independent [4]. We previously demonstrated inflammatory citrullination in the salivary glands of Sj£¿gren¡¯s syndrome patients that was partially dependent on iNOS. This enzyme is overexpressed in inflammatory cells and infiltrates of the acini and salivary epithelia, and the in situ NO overdrive may contribute to glandular damage [5]. TNF and other proinflammatory cytokines are frequently observed in the glandular tissues of these patients, and these factors may trigger the production of iNOS [6]. Although protein citrullination is an important event in rheumatoid arthritis pathogenesis [7, 8], this process may also occur in Sj£¿gren¡¯s syndrome.
%U http://www.hindawi.com/journals/ad/2013/548064/