Pathogenesis of Sjögren's syndrome.
OBJECTIVE
To summarize recent developments in our understanding of the pathogenesis of Sjögren's syndrome with a focus on the relationship between inflammation and exocrine dysfunction.


RESULTS
Animal models demonstrated the complex interactions between immunologic and nonimmunologic mechanisms in Sjögren's syndrome. Activation of the innate immune system can lead to exocrine dysfunction before or without significant inflammation, whereas in other models, salivary gland function is preserved despite intense inflammatory infiltrates. Primary or inflammation-related abnormalities in water channels contribute to the exocrinopathy. Activation of the innate immunity in patients is demonstrated by the upregulation of type-1 interferon-regulated genes (interferon signature) in peripheral blood and salivary glands and abnormal expression of B cell-activating factor and its receptors. Nonimmune mechanisms that may contribute to exocrine dysfunction include local and systemic androgen deficiency and autonomic nervous system dysfunction. Autoantibodies against the muscarinic acetylcholine receptors would provide a link between autoimmunity and exocrine dysfunction, but the data on the presence, frequency and physiologic affect of these antibodies remain controversial.


CONCLUSIONS
Recent discoveries from studies in patients with Sjögren's syndrome and animal models suggest a complex interplay between genetic factors, environmental and stochastic events that involve innate and adaptive immunity, hormonal mechanisms and the autonomic nervous system. Some of these findings suggest that exocrine gland dysfunction may precede autoimmunity or represent a process independent from inflammation in the pathogenesis of Sjögren's syndrome.
Nikolov
Nikolay P
NP
Sjögren's Syndrome Clinic, National Institute of Dental and Craniofacial Research (NIDCR), Molecular Physiology and Therapeutics Branch, National Institutes of Health (NIH), Bethesda, Maryland 20892, USA.
Illei
Gabor G
GG
D000818:Animals; D001323:Autoantibodies / Q000378:metabolism; D001341:Autonomic Nervous System / Q000503:physiopathology; D053264:B-Cell Activating Factor / Q000378:metabolism; D015984:Causality; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D016898:Interferon-alpha / Q000235:genetics / Q000378:metabolism; D008297:Male; D011976:Receptors, Muscarinic / Q000276:immunology; D012727:Sex Characteristics; D012859:Sjogren's Syndrome / Q000209:etiology* / Q000235:genetics / Q000276:immunology / Q000503:physiopathology
D001323:Autoantibodies; D053264:B-Cell Activating Factor; D016898:Interferon-alpha; D011976:Receptors, Muscarinic; C505719:TNFSF13B protein, human