The thesis is devoted to improving the diagnosis and prediction of the course of polyarteritis nodosa (PAN) and ANCA-associated vasculitis by determining the clinical and laboratory features including immunobiochemical markers of inflammation and the vascular wall damage. The study consists of retrospective and prospective analysis. Eighty patients with ANCA-associated vasculitis and 112 PAN patients were included in a retrospective study. Outcome data were collected for 49 patients with ANCA-associated vasculitis and 53 patients who had been diagnosed with PAN. Survival was evaluated as a function of the main demographics, clinical and laboratory parameters, and Birmingham Vasculitis Activity Score (BVAS) assessed at diagnosis.
There were no significant differences between PAN and ANCA-associated vasculitis in the median age of onset and clinical activity according to BVAS. The patients with PAN were predominantly males (65% vs 38% in the compared group, p<0.01). Fever (96% vs 86%), myalgia (79% vs 16%), weight loss (61% vs 45%), arthritis (48% vs 30%), cutaneous manifestations (44% vs 29%), peripheral nervous system involvement (31% vs 11%), diastolic arterial hypertension (30% vs 1.3%) and abdominal pain (13% vs 2.5%), occurred more often in pts with PAN (p<0.05), whereas pulmonary involvement (15 % vs 49%) was more frequent in compared group (p<0.01). Asthma, upper respiratory tract involvement, hemoptysis, ocular manifestations, and glomerulonephritis were found exclusively in patients with ANCA-associated vasculitis.
The median duration of follow-up was 62 months for ANCA-associated vasculitis and 92 months for PAN and 21 deaths were recorded (15 patients with PAN, 4 – MPA, and 2 – GPA). The predominant causes of deaths were multiple organ failure (47.6%), infections (28.6%), and renal failure (23.8%). Cumulative survival rates of PAN and ANCA-associated vasculitis at 1, 3, 5, and 10 years were 88.6, 84.2, 81.8, 68.2%, and 91.8, 87.6, 87.6, 76.7% respectively. The increased creatinine levels of more than 176 umol/l and the presence of hemorrhagic alveolitis are independent predictors of poor survival of patients with GPA and MPA. The age at onset of the disease of more than 60 years significantly reduces the survival of patients with PAN. Multivariate analysis showed that the presence of increased creatinine levels more than 140 umol/l and cardiac involvement were significant negative prognostic factors for PAN patient survival. Vasculitis activity detected by BVAS and other demographic, clinical, and laboratory parameters no effect on mortality.
Four serum proteins (alpha-actin-2, endothelin-1 (ET-1), elastin, and B-cell activating factor (BAFF)) representing different aspects of the pathogenesis of vasculitis were measured in 48 patients with primary systemic vasculitis (PSV) (granulomatosis with polyangiitis – 22, eosinophilic granulomatosis with polyangiitis – 9, microscopic polyangiitis – 6, polyarteritis nodosa – 11) and 26 healthy controls. The prospective study included 18 males and 30 females with a median age of 49. At the screening, 22 patients were without any treatment. The measuring alpha-actin-2, ET-1, elastin, and BAFF levels were performed at screening (in all patients and healthy controls) and 6.75±3.33 (M±SD) months after the beginning of induction therapy (in naïve patients).
The level of alpha-actin-2 in the group of patients with ANCA-associated vasculitis was twice as high as in the healthy controls (p<0.05). The elevated level of alpha-actin-2 (above 85.8 ng/ml) with high sensitivity (83%) and specificity (84%) allows the diagnosis of ANCA-associated vasculitis in patients suspected of these diseases. In patients with PSV who achieved remission or low disease activity after induction therapy, serum alpha-actin-2 levels are decreased twice (p<0.05), in contrast to the alternative group. А significant elevated serum ET-1 level is found in patients with kidney damage. The serum level of elastin is significantly higher in patients with polyarteritis nodosa compared with patients with ANCA-associated vasculitis, which can be used in the differential diagnosis of primary systemic vasculitis (sensitivity – 75%, specificity – 89%, p<0.01). There are significant differences in levels of BAFF between patients with BVAS≥24 and patients with BVAS≤11. According to ROC analysis evaluation of serum BAFF level distinguishes patients with active primary systemic vasculitis from patients with low activity or remission.
