Mechanisms and Classification
Normally, the immune system destroys foreign antigens or altered self-cells (e.g., tumor cells). In autoimmune diseases, this process malfunctions. Autoreactive lymphocyte clones are formed, and autoantibodies and cytotoxic T cells are generated against healthy tissues.
Diseases are divided into two main groups:
- Organ-specific. The attack targets a specific organ. Examples include autoimmune thyroiditis, type 1 diabetes mellitus, atrophic gastritis, and autoimmune hemolytic anemia.
- Systemic. Targets are autoantigens present in multiple tissues throughout the body. Examples include systemic lupus erythematosus (SLE), rheumatoid arthritis, and multiple sclerosis.
Frequently, a single individual may present with multiple concurrent autoimmune pathologies.
Etiology and Risk Factors
Autoimmune diseases have a multifactorial etiology, triggered by a combination of external and internal factors.
Exogenous (External) Factors:
- Infections, vaccination.
- Ultraviolet radiation (excessive sun exposure), hypothermia.
- Certain medications.
Endogenous (Internal) Factors:
- Genetics. Susceptibility is linked to major histocompatibility complex (HLA) genes and immunoglobulin genes.
- Hormonal status. Female sex hormones (estrogens) can provoke flares. For instance, SLE occurs up to 10 times more frequently in women, and patients' conditions often worsen during pregnancy or postpartum.
- Complement system defects. Impaired clearance of immune complexes and depletion of serum complement levels.
- Cytokine dysregulation. Imbalance between pro- and anti-inflammatory cytokines.
Role of Infections and Immune-Privileged Organs
Infectious agents can trigger pathology via two main pathways. The first is molecular mimicry, where microbial proteins structurally resemble human proteins, causing antibodies to mistakenly target host tissues. The second pathway involves the pathogen altering the structure of the body's own antigens, rendering them foreign to the immune system.
A special mechanism involves immune-privileged organs. Normally, certain tissues (brain, eye, thyroid gland, testes) are separated from the immune system by blood-tissue barriers, and lymphocytes do not typically contact them. If trauma or inflammation disrupts the barrier, the immune system encounters these antigens for the first time, perceives them as foreign, and launches an autoimmune reaction.
Principles of Treatment
The baseline therapeutic strategy aims to suppress the pathological immune response.
- Anti-inflammatory and cytotoxic drugs form the backbone of therapy.
- Glucocorticoids (GCs). Used during acute flares. Pulse therapy (ultra-high doses of GCs combined with cytotoxics) is an option, though it carries severe side effects.
- Targeted (biological) therapy. Includes anticytokine agents (blocking inflammatory mediators) and cellular receptor suppression.
- Aminoquinoline derivatives (hydroxychloroquine, chloroquine). Exhibit anti-inflammatory, antioxidant, and photoprotective properties. Prescribed in the absence of severe organ damage.