Role of ANCA in Pathogenesis
Antineutrophil cytoplasmic antibodies (ANCA) are detected in the majority of autoimmune vasculitides. Although the exact mechanism of their action is not fully elucidated, the following cascade is proposed: antibodies bind to components of the neutrophil cytoplasm, leading to activation of these cells. Activated neutrophils release hydrolytic enzymes that directly damage the vessel wall.
There are two main types of antibodies:
- cANCA (cytoplasmic): bind to proteinase 3, located in the azurophilic granules of neutrophils. They are most specific for granulomatosis with polyangiitis (detected in 70–99% of patients) and are considered a poor prognostic factor.
- pANCA (perinuclear): produce a characteristic granular staining pattern around the nucleus, with myeloperoxidase as their target. These antibodies are typical for microscopic polyangiitis and eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome).
Morphological Dependence on Vessel Caliber
Stereotypical pulmonary changes in vasculitis include hemorrhagic infarcts, necrotic foci, hemorrhages, and hemosiderosis. However, the specific morphological picture strictly depends on the caliber of the vessels involved in the pathological process:
- Medium and small branches of the pulmonary artery: inflammation is accompanied by thrombosis, leading to the development of classic pulmonary hemorrhagic infarcts.
- Small vessels (capillaries): their involvement causes alveolitis, capillaritis, diffuse hemorrhages, and subsequent hemosiderosis.
- Small branches of the bronchial artery: inflammation in this vascular bed leads to necrosis and destruction of the bronchial wall.
Major Nosologies Affecting the Lungs
Granulomatosis with Polyangiitis (Wegener's) A systemic necrotizing arteritis affecting the upper respiratory tract, respiratory tree, lung parenchyma, and kidneys. Isolated pulmonary involvement is extremely rare. It typically affects individuals around 50 years of age, with a peak incidence in winter. Macroscopically, multiple dark-red nodules and cavities are symmetrically identified in both lungs. The microscopic picture is represented by the histological triad: necrotizing polymorphocellular granulomas, vasculitis, and foci of necrosis. Without treatment, the disease progresses rapidly, leading to death from renal failure.
Microscopic Polyangiitis This disease belongs to the pulmonary-renal syndrome. Unlike classic polyarteritis nodosa, inflammation here extends down to arterioles, venules, and capillaries (including glomerular capillaries). Hemorrhagic alveolitis develops in the lungs—a combination of diffuse alveolar damage, capillaritis, hemorrhages, and infarcts. In late stages, carnification and pulmonary fibrosis develop. Men are affected 1.5 times more frequently, with a mean age of 56 years.
Eosinophilic Granulomatosis with Polyangiitis (Churg-Strauss Syndrome) An angiitis with granulomatous inflammation presenting with a diagnostic triad: bronchial asthma, blood eosinophilia (greater than 10%), and systemic vasculitis. The disease progresses through three stages: from allergic reactions (rhinitis, asthma) to systemic leukocytoclastic vasculitis and severe organ pathology. Specific infarcts with destructive thrombovasculitis, eosinophilic infiltration, and granulomas in the demarcation zone form in the lungs.
Vasculitides with Specific Pulmonary Affinity
Certain systemic vasculitides exhibit strict patterns of pulmonary vessel involvement:
- Polyarteritis Nodosa: a chronic systemic vasculitis of small and medium-sized arteries (associated with hepatitis B in 30% of cases). A critical diagnostic feature is that this disease never involves the pulmonary circulation or glomerular capillaries. Pulmonary vasculitis can occur only in branches of the bronchial artery. The classic morphological marker is the simultaneous presence of all stages of inflammation and healing within different vessels.
- Takayasu Arteritis: a giant-cell aortitis affecting predominantly young Asian females (under 40 years of age). In addition to the aortic arch, the pulmonary trunk is involved in 12–86% of cases. The walls of the affected vessels thicken, and their lumens become significantly narrowed.