Detection of cleaved alpha-fodrin autoantigen in Sjögren's syndrome: apoptosis and co-localisation of cleaved alpha-fodrin with activated caspase-3 and cleaved poly(ADP-ribose) polymerase (PARP) in labial salivary glands

Abstract

Sjögren's syndrome (SS) is a systemic autoimmune disease which targets the exocrine glands and is associated with autoantibodies. The mechanism of salivary gland destruction or autoantibody production is poorly understood but it is increasingly accepted that apoptosis plays a role.

Objective: The objective of this study is to demonstrate the presence of cleaved alpha-fodrin autoantigen and apoptosis in the salivary glands of patients with primary Sjögren's syndrome.

Methods: 18 patients with primary Sjögren's syndrome provided tissues from a labial salivary gland biopsy. Using terminal deoxynucleotidyl transferase mediated dUTP nick end labelling (TUNEL) assays to detect DNA fragmentation followed by sequential immunoperoxidase assays in the same patient biopsy to detect cleaved alpha-fodrin, Poly(ADP-ribose) polymerase (PARP), and caspase-3, we show a co-localisation between apoptotic markers and disease.

Results: Co-localisation of cleaved alpha-fodrin, PARP and caspase-3 expression was demonstrated primarily in the ducts along with DNA fragmentation in 16/18 salivary gland biopsies from Sjögren's syndrome patients. None of these apoptotic markers was strongly expressed in healthy tissues.

Conclusion: Apoptotic signals may provide useful therapeutic targets and cleaved alpha-fodrin may prove to be a marker of disease in primary Sjögren's syndrome. Further studies are required to ascertain the specific association of cleaved alpha-fodrin with primary and secondary Sjögren's syndrome.