Apoptosis and estrogen deficiency in primary Sjögren syndrome.
OBJECTIVE
Primary Sjögren syndrome is an autoimmune disorder characterized by lymphocytic infiltrates and destruction of the salivary and lacrimal glands, and systemic production of autoantibodies to the ribonucleoprotein particles SS-A/Ro and SS-B/La. The purpose of this review is to discuss recent advances in the pathogenesis of primary Sjögren syndrome.


RESULTS
Although several candidate autoantigens including alpha-fodrin have been reported in Sjögren syndrome, the pathogenic roles of the autoantigens in initiation and progression of SS are still unclear. It is possible that individual T cells activated by an appropriate self antigen can proliferate and form a restricted clone. Recent evidence suggests that the apoptotic pathway plays a central role in tolerizing T cells to tissue-specific self antigen, and may drive the autoimmune phenomenon. Cleavage of certain autoantigens during apoptosis may reveal immunocryptic epitopes that could potentially induce autoimmune response. The studies reviewed imply that Fas-mediated cytotoxicity and caspase-mediated alpha-fodrin proteolysis are involved in the progression of tissue destruction in Sjögren syndrome. Fas ligand (FasL), and its receptor Fas are essential in the homeostasis of the peripheral immune system. It can be considered that a defect in activation-induced cell death of effector T cells may result in the development of autoimmune exocrinopathy in Sjögren syndrome.


CONCLUSIONS
Although the mechanisms by which estrogen deficiency influences autoimmune lesions remain unclear, it is possible that antiestrogenic actions might be a potent factor in the formation of pathogenic autoantigens.
Hayashi
Yoshio
Y
Department of Pathology, Tokushima University School of Dentistry, Tokushima, Japan. hayashi@dent.tokushima-u.ac.jp
Arakaki
Rieko
R
Ishimaru
Naozumi
N
D000818:Animals; D017209:Apoptosis; D002352:Carrier Proteins / Q000378:metabolism; D004967:Estrogens / Q000172:deficiency* / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008840:Microfilament Proteins / Q000378:metabolism; D012859:Sjogren's Syndrome / Q000209:etiology* / Q000378:metabolism / Q000473:pathology*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D013049:Spectrin
D002352:Carrier Proteins; D004967:Estrogens; D008840:Microfilament Proteins; D013049:Spectrin