[Effects of pulse-therapy on natural anticoagulant system of the endothelium in nonspecific aortoarteritis]. / Vliianie pul's-terapii na estestvennuiu antikoaguliantnuiu sistemu éndoteliia pri nespetsificheskom aortoarterite.

AIM: To investigate the influence of pulse-therapy on anticoagulant system of the endothelium in patients with nonspecific aortoarteritis. MATERIAL AND METHODS: Eleven patients (9 females and 2 males, mean age 33.4 +/- 8.8 years, the disease duration 5.8 +/- 5.7 years) with nonspecific aortoarteritis were examined. 9 patients had the third anatomic type of the disease with affection of the aortic arch and abdominal aorta vessels, 2 patients had the first anatomic type with isolated affection of the aortic arch. The patients received a standard three day course of pulse-therapy (PT) with glucocorticosteroids (GCS) (metipred in a dose 1000 mg/day or dexametasone in a dose 2 mg/kg/day) with a single dose of cytostatic (CS) (cyclophosphamide in a dose 10 mg/kg b.w.) during the first infusion. Further PT consisted of monthly single infusion of GCS and CS in the above doses for 9 to 12 months. Examination of the patients was carried out before the treatment and on the treatment day 4 and 20 and follow-up month 3, 6 and 12. Estimation of clinical activity was carried out according to BVAS. Levels of protein C, S, antithrombin III were measured by ELISA in plasma. Activities of protein C, antithrombin III and plasminogen were determined by the optical assay with chromogenic substrates. RESULTS: Before the start of the treatment BVAS was 6.8 +/- 4.3. During the follow-up mean scores of BVAS were significantly lower than before the pulse-therapy (2.7 +/- 2.2; 2.5 +/- 3.9; 3.1 +/- 5.1; 1.8 +/- 2.6 and 1.7 +/- 1.7, respectively; p < 0.05). Prior to the treatment, a mean level of protein C was 86.6 +/- 37.5% and range of its activity 175.2 +/- 112.9%. On the fourth day after pulse-therapy a mean concentration of protein C increased (128.8 +/- 29.0%; p < 0.05) while activity of protein C tended to a decrease on the 20th day (99.2 +/- 17.6; p > 0.05). There were no significant differences in the levels of protein S, antithrombin III and its activity, activity of plasminogen in the course of PT. CONCLUSION: PT has a good anti-inflammatory effect in the absence of unfavorable influence on anticoagulant system of the endothelium in patients with nonspecific aortoarteritis.

[Antibodies to proteinase-3 and myeloperoxidase in systemic vasculitis]. / Antitela k proteinaze-3 i mieloperoksidaze pri sistemnykh vaskulitakh.

AIM: To investigate occurrence and diagnostic significance of antibodies to proteinase-3 (aPR-3) and myeloperoxidase (aMPO) in systemic vasculitis (SV). MATERIAL AND METHODS: A total of 98 patients with different forms of SV were examined: nonspecific aortoarteritis (NAA, n = 18), nodular polyarteritis (NP, n = 18), Wegener granulomatosis (WG, n = 20), obliterating thrombangiitis (OT, n = 21), and hemorrhagic vasculitis (HV, n = 21). Eight patients with primary antiphospholipid syndrome (PAPS) and 20 donors comprised a control group. aPR-3 and aMPO were detected by solid-phase enzyme immunoassay using kits ORGenTec Diagnostica GmbH. RESULTS: aPR-3 were detected in 1 (5.6%) patient with NP and in 3 (14.3%) patients with HV. aPR-3 were detected in 13 (65%) of 20 patients with WG being significantly more frequent not only vs controls (0%) but in some forms of SV and PAPS (p < 0.05). Mean aPR-3 level in 13 WG patients was significantly higher than in 4 patients (1 with NP and 3 with HV) the sera of whom also contained aPR-3. 84.6% patients with WG had higher concentrations of aPR-3, this is significantly more frequently than in the comparison group. In NP and HV these autoantibodies were encountered in the serum only in moderate or low concentrations in patients with high clinicolaboratory activity of the disease. In WG patients there was no correlation between aPR-3 presence, form of the disease and basic clinical manifestations, but mean values of index of clinical activity of vasculitis were significantly higher in patients with aPR-3 than in those free of them. Concentration of aPR-3 in an active phase of the disease was significantly higher than in patients in remission. Moreover, aPR-3 were detected in 83.3% cases in active vasculitis and in 37.5% patients without it. Detection of aPR-3 in WG group was associated with mean sensitivity and good specificity. In examination of the patients in an active phase specificity rose but sensitivity fell. Optimal results were obtained in estimation of aPR-3 level. Thus, in moderate or high concentration, aPR-3 have good sensitivity and high specificity for diagnosis of WG, in a high titer (> 15 U/ml) they are highly sensitive and specific for this vasculitis. aMPO were detected in 1 of 18 patients with NP, in 1 of 21--with OT, in 3 of 21--with HV and in 2 of 21--with NAA. None patients with WG or PAPS had aMPO. aMPO were detected in NP and HV in high activity of inflammation. Part of the patients had affected kidneys. CONCLUSION: Thus, WG is characterized by the presence and high concentration of aPR-3. In the latter case aPR-3 have high (100%) sensitivity and specificity for diagnosis of WG. Detection of aPR-3 can be used as an additional laboratory test for diagnosis of WG and estimation of its activity.

[Pulse-therapy with glucocorticoids and cyclophosphamide in the treatment of thromboangiitis obliterans]. / Pul's-terapiia gliukokortikoidami i tsiklofosfamidom v lechenii obliteriruiushchego trombangiita.

Effectiveness of glucocorticoid and cyclophosphamide pulse-therapy was studied in patients with thrombangitis abliterans (TA). We examined 28 males. All of them were treated with antiplatelet agents and vasodilators in standard doses. In addition, 16 patients received a standard three-day scheme of a glucocorticoid and cyclophosphamide pulse-therapy. The examination of the patients was carried out before the treatment and in a month. Estimation of clinical activity was made according to the BVAS index, serum levels of C-reactive protein (CRP) and von Willebrand factor antigen (VWF-Ag), ESR. Before the start of the treatment there were no significant differences in the values of BVAS, ESR and CRP between the groups. In a month, BVAS index, concentrations, the rate of high serum levels of CRP and frequency of amputations were significantly reduced in patients treated with pulse-therapy. So, this pulse-therapy has a considerable anti-inflammatory effect and decreases frequency of amputations in thrombangiitis obliterans.

[Antibodies to phospholipids and the vascular endothelium in nodular polyarteritis]. / Antitela k fosfolipidam i éndoteliiu sosudov pri uzelkomov poliarteriite.

Clinical significance of antibodies to phospholipids (aPL) and vascular endothelium (aVE) was evaluated in 20 patients (9 women and 11 men aged 36 +/- 10.8 years) with nodular polyarteritis (NP) corresponding to classification criteria of the USA Rheumatology College. Antibodies to cardiolipin (aCL) (IgG and IgM) and to beta 2-glycoprotein (beta 2-GP1) (IgG) were titered by solid-phase enzyme immunoassay. Total serum level of aVE (IgG + IgM + IgA) was measured by solid-phase enzyme immunoassay using Eahy. 926 endothelial hybrydoma cell culture. Anticardiolipin antibodies were detected in 11 (55%) of 20 patients, 3 of these had IgG aCL, 4 IgM aCL, and 4 both antibody isotypes. Serum titers of all aCL were moderate in all cases. No antibodies to beta 2-GP1 were detected in any of the patients. Total serum endothelial activity varied from 0 to 89.7% in patients with NP. Mean aVE level was 24.45 +/- 21.2%, which was significantly higher than in donors (p < 0.001). In 4 (26.7%) of 15 patients with NP total level of aVE surpassed the upper threshold normal value. The presence of aCL directly correlated with the presence of reticular livedo (r = 0.54, p < 0.05), but not with any other clinical laboratory manifestations of the disease, including thrombotic complications (deep thrombosis of lower limb veins, stroke, myocardial infarction), renal involvement, increased erythrocyte sedimentation rate, increased concentrations of von Willebrand factor antigen and C-reactive protein, or angiitis activity. Vascular endothelial antibodies directly correlated with renal involvement (r = 1.00, p < 0.01), distal gangrene of the limb (r = 0.83, p < 0.01), and angiitis activity (r = 0.78, p < 0.001), with high level of von Willebrand factor antigen and increased erythrocyte sedimentation rate (r = 0.66 and r = 0.64, respectively; p < 0.01), but not with aCL (r = 0.43, p > 0.05) of any isotype (aCL IgG r = -0.01; r = 0.34; p < 0.05). All patients with aVE had aCL in the serum (aCL IgG in 1, aCL IgG and IgM in 1, and aCL IgM in 2 patients). The results indicate different significance of a CL and aVE in NP; the mechanisms of realization of their pathogenetic potential are still to be investigated.