Causes And Risk Factors
Symptoms of Sjögren syndrome develop when salivary glands and lacrimal (tear-producing) glands are damaged by the immune system (Rischmueller 2016).
Cells that line salivary glands and produce saliva, called epithelial cells, are major targets of the autoimmune attack. Epithelial cells in other organs such as the liver, kidneys, lungs, and thyroid are also frequently damaged by the immune system in Sjögren patients (Rischmueller 2016; Kyriakidis 2014; Mitsias 2006).
Sjögren syndrome is a multifactorial disease caused by interaction among genetic and environmental factors. Several viruses have been implicated in Sjögren syndrome, and multiple potential mechanisms of disease have been proposed (Mariette 2016; Mavragani 2013; Catanzaro 2014; Igoe 2013).
Genetics and family history. Sjögren syndrome and other autoimmune disorders often cluster in families. Immediate family members of Sjögren patients have up to 12 times the risk of developing Sjögren syndrome compared with the general population (Kuo 2015).
Genetic predisposition to Sjögren syndrome and a number of other autoimmune diseases is associated with variants of the human leukocyte antigen (HLA) gene complex (Rischmueller 2016; Ferro 2016; Tincani 2013; Cruz-Tapias 2012).
Viruses. Viral infections may trigger Sjögren syndrome. Potential viral triggers include (Nakamura 2016; Kurien 2017; Nakamura 2015; Origgi 1988; Igoe 2013):
- Cytomegalovirus (CMV)
- Epstein-Barr virus (EBV)
- Human T-lymphotropic virus type 1 (HTLV-1)
- Hepatitis C virus (HCV)
EBV reactivation may play a role in Sjögren syndrome initiation and progression. EBV infects over 90% of adults worldwide, but in most people the virus becomes inactive after infection (Petrova 2010; Ho 1988). Increased levels of EBV virus and antibodies have been noted in Sjögren patients, suggesting that ongoing EBV activity may trigger autoimmune processes (Kurien 2017; Draborg 2013).
Gender. Sjögren syndrome is nine times more common in women than men. The gender difference may be related to hormonal factors (Kurien 2017; Rubtsov 2010; Mavragani 2014).
Age. While primary Sjögren syndrome can occur at any age, its onset is most common in those aged 55 to 65 (Rischmueller 2016), and risk remains elevated into older age (Patel 2014).
Unlike primary Sjögren syndrome, secondarySjögren occurs in people who have another autoimmune disease (Mariette 2016). A variety of other disorders and conditions have also been associated with Sjögren syndrome (Catanzaro 2014; Bartoloni 2015; Quartuccio 2015; Wong 2014; Martinez 2011; Francois 2016; Kim-Lee 2015; Salliot 2007; Ohtsuka 1992; Selmi 2012; Lindvall 2002; Karp 2010; Jara 2007; Pedro-Botet 1993; Ziavra 2000; Maripuri 2009; Ebert 2012; Nilsson 2015; Baruch 1977; Sarkar 2009; Mialon 1997; Alenghat 2016).
Autoimmune Diseases Associated with Sjögren Syndrome
Other Diseases and Disorders Associated with Sjögren Syndrome
Cytomegalovirus (CMV) and Sjögren Syndrome
About half of the US population has been exposed to cytomegalovirus (CMV), a member of the herpesvirus family (Bate 2010). CMV may play an important role in the onset and progression of certain autoimmune disorders, including Sjögren syndrome (Halenius 2014; Varani 2011; Schuster 2014).
When healthy adults become infected with CMV, they usually experience no symptoms or mild flu-like symptoms. Once a person has been infected with CMV, the virus remains in the body throughout life (Sansoni 2014; Lancini 2014).
Although chronic CMV may not cause significant symptoms in most people, its lingering presence can contribute to a type of immune system dysfunction known as immune senescence (Sansoni 2014; Savva 2013; Chou 2013). Premature senescence of the immune system, which may be induced by CMV, has been proposed to be a contributing factor in autoimmune disorders (Solana 2012; Prelog 2006; Thewissen 2005).
CMV infects the salivary glands, a primary target of autoimmune attack in Sjögren syndrome. In fact, CMV was originally called “salivary gland virus” (Shillitoe 1982; Smith 1956).
Studies in mice have demonstrated an association between chronic CMV infection and the development of an autoimmune disease with features of Sjögren syndrome. These Sjögren-like features include buildup of immune cells and severe inflammation in the salivary and lacrimal (tear) glands, production of autoantibodies, progressive loss of salivary gland function, and decreased secretion of saliva and tears (Schuster 2014; Ohyama 2006).
An article titled A Common Virus That May Accelerate Immune Senescence, published in the January 2015 issue of Life Extension magazine, discusses the effects of long-term CMV infection in greater detail and explores interventions that may help prevent some of the problems associated with this common virus.