Introduction to Sjogren's Syndrome

Causes of Sjogren's Syndrome

Sjogren's syndrome is an autoimmune condition marked by the presence of antinuclear antibodies and rheumatoid factor. Other antibodies (anti-Ro) are associated with extraglandular (outside of the glands) manifestations of Sjogren's syndrome. Organ-specific antibodies are found in approximately 60% of patients with Sjogren's syndrome. Sjogren's syndrome is associated with chronic stimulation of the immune system, specifically B-cells and T-cells. Histologically, focal lymphocytic infiltrates (a collection of fluid and cells in the tissue) are located mostly around glandular ducts (salivary and lacrimal ducts) and other exocrine glands (skin, lungs, gastrointestinal tract, and vagina). The infiltrate contains B-cells, T-cells, and plasma cells. Eventually, the infiltrate grows and occupies the inner epithelium (inner lining of the gland) which leads to dysfunction and enlargement of the gland.

Although the exact cause of Sjogren's syndrome remains unknown, several theories have been proposed in an attempt to explain the pathophysiology of the disorder. These include:

• Chronic inflammation
• Cellular apoptosis
• Autonomic dysfunction
• Genetic predisposition
• Neurotransmitter abnormality

Chronic Inflammation Theory

The chronic inflammation theory proposes that continuous infiltration of immune cells (lymphocytes, monocytes, and plasma cells) into the salivary and lacrimal glands eventually results in replacement of normal glandular tissue with chronic inflammatory cells causing progressive dysfunction of the glands with reduced production and secretion of saliva and tears.

Evidence shows that defective glandular tissue seems to be inherently related to the development of antigens which, for unknown reasons, instead of being seen as part of the body, become the focus of an autoimmune attack, bringing on the continued infiltration of lymphocytes. In addition, the attacking cells (B/T-lymphocytes) fail to undergo normal apoptosis (cell death) which results in their proliferation and may be a factor in prolonging the autoimmune process.

Cellular Apoptosis Theory

The term "apoptosis" refers to death of a cell and is a form of cellular "self-destruction". It has been hypothesized that apoptosis of glandular cells, especially ductal cells, may eventually lead to the glandular dysfunction that is responsible for the classical dry eye and dry mouth symptoms of Sjogren's syndrome. Apoptosis of glandular cells may be triggered by viral infections including:

• Epstein-Barr virus (EBV) infection
• Hepatitis C virus (HCV) infection
• Human Immunodeficiency Virus (HIV) infection

Autonomic Dysfunction Theory

This theory proposes that a dysfunction of the autonomic nervous system, the part of the nervous system that controls the production and secretion of saliva and tears, may be a major contributing factors leading to glandular dysfunction and the development of Sjogren's syndrome.

Genetic Predisposition Theory

Proponents of this theory believe that some people who develop Sjogren's syndrome may be genetically predisposed to this disorder. Evidence supporting a genetic predisposition for Sjogren's syndrome has been linked to the major histocompatibility complex genes known as human leukocyte antigens (HLAs). An increased prevalence of specific HLA genes, including HLAB8, DR3, and DRw52, has been found in patients with primary Sjogren's syndrome.

Genetic evidence has also recently indicated that defective glandular development may predispose an individual to developing epithelial glandular cells that secrete certain immuno-stimulatory agents which are not seen in patients who do not have Sjogren's syndrome.

Neurotransmitter Abnormality

Biopsies of the salivary glands of patients with Sjogren's syndrome have shown that while only 50-60% of glandular tissue is destroyed, the symptoms of dry mouth and dry eye are as severe as if there was only minimal healthy tissue remaining. This puzzle has led some scientists to theorize that some aspect of the immune cells that are produced impair the release of the neurotransmitter acetylcholine and that this may account for the cessation or severe reduction of saliva or tear production even in the presence of healthy glandular tissue.