Sjögren's syndrome

Clinical and morphological picture

The pathological process in this disease is progressive. The core of the problem lies in the interaction between the autoantibodies produced by the body and the antigens of its own exocrine glands.

This interaction triggers a cascade of reactions leading to serious consequences:

• Destruction of glandular tissue: Salivary and lacrimal glands are affected first. Their structure is progressively destroyed, leading to a sharp decrease in secretion production (hypofunction).
• Ocular involvement: Lack of tear fluid provokes the development of keratoconjunctivitis sicca — a specific inflammation of the cornea and conjunctiva.
• Generalized dryness: As the disease progresses, patients experience pronounced dryness of various mucous membranes. The mucous membranes of the nose, oral cavity, and genitals are involved, significantly reducing the quality of life and creating favorable conditions for secondary complications.

Immunopathogenesis and cytokine cascade

The development of Sjögren's syndrome is multifactorial. One of the key triggers initiating the pathological process is considered to be the presence of a chronic viral infection in the body.

The tissue damage mechanism can be represented as a clear sequence:

1. Tissue infiltration: Specific immune cells — CD4+ T lymphocytes — begin to dominate in the foci of exocrine gland inflammation.
2. Release of mediators: These cells initiate a powerful cytokine cascade. The active synthesis of proinflammatory molecules begins: interleukin-1 (IL-1), interleukin-6 (IL-6), interferon-gamma (IFN-γ), and tumor necrosis factor-alpha (TNF-α).
3. Epithelial alterations: Under the influence of high concentrations of these cytokines, glandular epithelial cells change their properties, inducing the expression of class II HLA molecules on their surface.
4. Closing the vicious cycle: The appearance of class II HLA molecules on cells where they are atypical (epithelial cells) leads to hyperactivation of T and B lymphocytes. This, in turn, causes a sharp increase in antibody production, including massive generation of autoantibodies that continue to destroy the gland.

Predisposing factors and diagnostics

Why do some patients develop this disease while others do not? Internal predisposing factors of the body play a huge role:

• Genetic factors: A strict association of the disease with certain major histocompatibility complex antigens has been proven. Specifically, these are the carriage of HLA-DR3, -DQ1, and -DQ2 alleles.
• Hormonal factors: Estrogens have a significant influence on the development of the autoimmune process, which explains the gender-specific distribution of the pathology.

To confirm the diagnosis in clinical practice, clinicians rely on two main pillars:

• Laboratory criteria: Patients' blood is routinely screened for specific markers. These include autoantibodies to nuclear antigens and rheumatoid factor.
• Histological criteria: Microscopic examination of a biopsy from the affected glandular tissue reveals characteristic foci of lymphoid infiltration, confirming the autoimmune nature of the inflammation.

Briefly: answers to topical questions

Class and exam questions

What else to study on this topic

• The role of chronic viral infection as a trigger of the autoimmune response
• Mechanisms of class II HLA induction on epithelial cells by cytokines
• Features of the interaction between CD4+ T lymphocytes and B lymphocytes in glandular tissue
• The influence of estrogens on the severity of immunoinflammatory changes
• Histological picture: stages of lymphoid infiltration of exocrine glands

Other topics in the "Pathology of the Immune System" section

Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.