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.
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.


CONCLUSIONS
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.
Wang
Yan
Y
Department of Oral Biology, School of Dentistry, University of Missouri-Kansas City, Kansas City, MO 64108, USA.
Virji
Adi S
AS
Howard
Paul
P
Sayani
Yaseen
Y
Zhang
Jianghong
J
Achu
Paul
P
McArthur
Carole
C
D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000276:immunology; D001324:Autoantigens / Q000032:analysis*; D002352:Carrier Proteins / Q000032:analysis / Q000276:immunology*; D053148:Caspase 3 / Q000032:analysis*; D053938:DNA Fragmentation; D005260:Female; D006801:Humans; D008046:Lip / Q000378:metabolism; D008297:Male; D008840:Microfilament Proteins / Q000032:analysis / Q000276:immunology*; D008875:Middle Aged; D011064:Poly Adenosine Diphosphate Ribose / Q000032:analysis*; D012469:Salivary Glands / Q000737:chemistry / Q000276:immunology*; D012859:Sjogren's Syndrome / Q000276:immunology*; D013049:Spectrin
D001324:Autoantigens; D002352:Carrier Proteins; D053148:Caspase 3; D008840:Microfilament Proteins; D011064:Poly Adenosine Diphosphate Ribose; D013049:Spectrin