Symptoms and Complications
- Fatigue (79%)
- Dry eyes (75%)
- Dry mouth (73%)
- Joint pain (65%)
- Trouble sleeping (64%)
- Increased rate of neonatal lupus erythematosus with congenital heart block requiring a pacemaker in pregnant women with anti-Ro/SS-A and anti-La/SS-B antibodies
- Type I cryoglobulinemia
- Affection of organs such as the liver, pancreas, kidneys, lungs, and central nervous system

Associated Conditions
- Celiac disease
- Fibromyalgia
- Systemic lupus erythematosus (lupus)
- Autoimmune thyroiditis
- Multiple sclerosis and spondyloarthropathy
- Several malignancies, principally non-Hodgkin lymphoma

Causes and Pathogenesis
- Combination of genetics and an environmental trigger such as exposure to a virus or bacterium
- Can occur independently (primary Sjögren's syndrome) or as a result of another connective tissue disorder (secondary Sjögren's syndrome)
- Association with other autoimmune diseases such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), or systemic sclerosis
- Lack of fully elucidated pathogenetic mechanisms
- Immune system-mediated loss of exocrine glands
- Infiltration of lymphocytes causing glandular dysfunction
- Association with increased levels of IL-1RA in cerebrospinal fluid (CSF)
- Interleukin 1 system involvement and cytokine-induced sickness behavior

Genetic Predisposition and Environmental Triggers
- The major histocompatibility complex/human leukocyte antigen (MHC/HLA) region is significantly associated with primary Sjögren's syndrome.
- A genome-wide association study identified six independent loci associated with primary Sjögren's syndrome.
- These loci include IRF5, STAT4, BLK, IL12A, TNIP1, and CXCR5.
- HLA-DR and HLA-DQ alleles are involved in the pathogenesis of Sjögren's syndrome.
- HLA class II alleles are associated with specific subsets of autoantibodies.
- Glandular viral infection can activate the innate immune system through toll-like receptors.
- Epstein-Barr virus (EBV), human T-lymphotropic virus 1, and hepatitis C virus have been implicated in Sjögren's syndrome.
- EBV reactivation is common in Sjögren's patients, indicating viral replication and immune response in target organs.
- The exact mechanisms of EBV reactivation in Sjögren's lesions are not fully understood.
- Other environmental factors may also contribute to the development of Sjögren's syndrome.

Autoantibodies and Epigenetic Abnormalities
- Loss of B-cell tolerance leads to the production of autoantibodies.
- Anti-SSA/Ro and anti-SSB/La antibodies are associated with Sjögren's syndrome.
- Seropositivity for anti-Ro and anti-La antibodies is linked to greater disease severity and longer duration.
- These antibodies are abundant in the salivary glands of Sjögren's patients.
- Their role in the pathogenesis of Sjögren's syndrome is essential.
- Epigenetic abnormalities may play a key role in the pathogenesis of autoimmune diseases, including Sjögren's syndrome.
- DNA methylation, histone acetylation, and microRNA expression are potential epigenetic mechanisms involved.
- Research in this area is limited.
- Further studies are needed to understand the impact of epigenetic abnormalities on Sjögren's syndrome.
- Targeting epigenetic modifications could be a potential therapeutic approach.

Ethnic Variations
- Patients of different ethnic origins carry different HLA-susceptibility alleles.
- HLA-DR and HLA-DQ alleles are involved in Sjögren's syndrome pathogenesis.
- Northern and Western European and North American patients have a high prevalence of B8, DRw52, and DR3 genes.
- HLA class II alleles are associated with specific subsets of autoantibodies.
- Ethnic variations may contribute to differences in disease presentation and severity.

Sjogren's syndrome (Wikipedia)

Not to be confused with Sjögren–Larsson syndrome and Marinesco–Sjögren syndrome.

Sjögren syndrome or Sjögren's syndrome (SjS, SS) is a long-term autoimmune disease that affects the body's moisture-producing glands (lacrimal and salivary), and often seriously affects other organ systems, such as the lungs, kidneys, and nervous system.

Sjögren's syndrome
Other names	Sjögren's syndrome, sicca syndrome
Image with a microscope of focal lymphoid infiltration in the minor salivary gland associated with Sjögren's syndrome.
Pronunciation	UK: /ˈʃɜːɡrɛn/, US: /ˈʃoʊɡrɛn/ Swedish: [ˈɧø̂ːɡreːn]
Specialty	Immunology, rheumatology
Symptoms	Dry mouth, dry eyes, other areas of dryness
Complications	Lymphoma
Usual onset	Middle age
Duration	Long term
Causes	Autoimmune disease (unknown cause)
Diagnostic method	Tissue biopsy, blood tests
Differential diagnosis	Medication side effect, anxiety, sarcoidosis, amyloidosis
Treatment	Artificial tears, medications to reduce inflammation, surgery
Prognosis	Normal life expectancy
Frequency	~0.7%