Sjögren’s Syndrome: Causes

Pathogenesis (disease development)

Sjögren’s syndrome is one of the systemic autoimmune diseases (excessive reaction of the immune system against the body’s own tissues) from the group of collagenoses, which leads to a chronic inflammatory disease or destruction of the exocrine glands, whereby the salivary and lacrimal glands are most frequently affected. Histologically (by fine tissue), there is lymphocyte infiltration (interspersion of the mucosa or salivary glands with lymphocytes/belonging to the white blood cells), disruption of the ductal system, and atrophy (shrinkage) of the parenchyma (tissue) of the salivary glands.

Etiology (causes)

The causes of the primary form of Sjögren’s syndrome are unknown.

Biographic causes

  • Genetic burden – Genes: HLA-associated (HLA-DR2, HLA-DR3).
    • Genetic risk dependent on gene polymorphisms:
      • Genes/SNPs (single nucleotide polymorphism):
        • Genes: STAT4, TNPO3
          • SNP: rs7574865 in the gene STAT4
            • Allele constellation: GT (1.55-fold).
            • Allele constellation: TT (2.4-fold)
          • SNP: rs10488631 in the gene TNPO3
            • Allele constellation: GT (1.7-fold).
            • Allele constellation: GG (3.4-fold)
  • Hormonal factors – climacteric (menopause in women) and postmenopause (period that begins when menstruation has been absent for at least a year).

Disease-related causes – secondary Sjögren’s syndrome.

  • Hepatitis B, C
  • Collagenoses
  • Lupus erythematosus (group of autoimmune diseases in which the formation of autoantibodies occurs).
  • Primary biliary cholangitis (PBC, synonyms: non-purulent destructive cholangitis; formerly primary biliary cirrhosis) – relatively rare autoimmune disease of the liver (affects women in about 90% of cases); begins primarily biliary, i.e. at the intra- and extrahepatic (“inside and outside the liver“) bile ducts, which are destroyed by inflammation (= chronic non-purulent destructive cholangitis). In the longer course, the inflammation spreads to the entire liver tissue and eventually leads to scarring and even cirrhosis; detection of antimitochondrial antibodies (AMA); PBC is frequently associated with autoimmune diseases (autoimmune thyroiditis, polymyositis, systemic lupus erythematosus (SLE), progressive systemic sclerosis, rheumatoid arthritis); Associated with ulcerative colitis (inflammatory bowel disease) in 80% of cases; long-term risk of cholangiocellular carcinoma (CCC; bile duct carcinoma, bile duct cancer) is 7-15%.
  • Rheumatoid arthritis – chronic inflammatory multisystem disease, usually manifested in the form of synovitis (inflammation of the synovial membrane).