Causes of Immune Aggression
The development of the disease begins with a breakdown of natural immunological tolerance. Key factors in this process include polyclonal lymphocyte activation and congenital or acquired defects in cell apoptosis. Various microbial superantigens can serve as additional triggers initiating the pathological process.
Cytokines play a crucial role in pathogenesis. In SLE, there is a pronounced overproduction of $T_H2$-type cytokines—primarily IL-4, IL-6, and IL-10. It is their excess that leads to the uncontrolled hyperactivation of B lymphocytes, which begin massive synthesis of autoantibodies.
Spectrum of Produced Autoantibodies
In lupus, the immune system loses specificity and begins producing antibodies against a wide variety of the body's own structures. Depending on the target, several groups of autoantibodies are distinguished:
- Antinuclear antibodies (ANAs): directed against multivalent nucleoprotein complexes, such as nucleosomes and ribonucleoproteins.
- Anticytoplasmic antibodies: attack structures inside the cell.
- Against surface structures: their targets are membrane components of cells that have undergone apoptosis (programmed cell death).
- Against blood cells: antibodies destroy erythrocytes, platelets, leukocytes, and lymphocytes, clinically manifesting as severe cytopenias.
- Antiphospholipid antibodies: a specific group of antibodies whose circulation inevitably causes dangerous thrombotic disorders.
Mechanisms of Tissue Destruction
Systemic inflammation is sustained through multiple pathways simultaneously. First, immune complexes deposit in healthy tissues, causing complement system activation and leukocyte recruitment. Second, the vascular endothelium is damaged by cytokines (specifically IL-1 and TNF-α). An additional contribution comes from an increased pool of $T_H17$ lymphocytes: IL-17 secreted by them significantly enhances inflammation and accelerates organ damage (kidneys, lungs, joints, CNS).
Chronification of the process is maintained by a positive feedback loop (vicious cycle of inflammation). This molecular cascade consists of five steps:
- Complex aggregates form, including antimicrobial peptides (cathelicidin), components of destroyed cells (DNA, HMGB1 protein), and DNA-specific IgG autoantibodies.
- Dendritic cells recognize and capture these aggregates via the FcγRIIa receptor.
- Inside the dendritic cell, Toll-like receptor 9 (TLR9) is activated.
- Receptor activation induces potent secretion of interferon-alpha (IFN-α).
- The release of IFN-α stimulates a new wave of autoantibody formation, immune complex assembly, and complement activation, closing the loop.
Clinical and Laboratory Diagnostics
Diagnosis is based on identifying specific markers and assessing tissue damage. In addition to classic cutaneous manifestations (dermatitis and butterfly rash) and serositis (inflammation of serous membranes), the following parameters are evaluated in the laboratory:
- Immunofluorescence (IF): a classic method for detecting antinuclear antibodies.
- Assay for specific markers: searching for antibodies against double-stranded DNA.
- Skin biopsy analysis: reveals characteristic deposits of IgG and IgM class immunoglobulins in affected tissues.
- Effusion analysis: contents of serous cavities (pericardial, pleural, peritoneal) localize immune complexes and reveal complement components (C3 and C4).
- Cerebrospinal fluid (CSF) analysis: in neurological manifestations of SLE, specific LE cells—neutrophils that have phagocytosed nuclear material—are detected.