[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.

[Serum neopterin in hemorrhagic vasculitis]. / Neopterin syvorotki krovi pri gemorragicheskom vaskulite.

Out of 12 patients with hemorrhagic vasculitis (HV) having the disease for 3-3.2 years (5 males and 7 females aged 18-55 years, mean age 34 +/- 13.8 years) renal affection was found in 3 (25%) patients. Renal function was normal in all the patients. One patient had nephrotic and two had mixed nephritis. One patient had gastrointestinal lesions. Serum neopterin was measured by radioimmunoassay. Mean concentration of serum neopterin was significantly higher than in donors (9.15 +/- 6.82 nmol/l and 5.2 +/- 2.1 nmol/l, respectively). A high neopterin level was found in 2 (67%) of 3 patients with nephritis and in 1(11%) of 9 patients free of nephritis. Mean neopterin was significantly higher in 3 patients with renal disorders than in the comparison group. A positive correlation existed between neopterin level and the clinical activity index, ESR, IgA, IgG CIC concentrations.

[Antibodies to phospholipids and ischemic disorders of cerebral circulation in young age]. / Antitela k fosfolipidam i ishemicheskie narusheniia mozgovogo krovoobrashcheniia v molodom vozraste.

Antibodies to phospholipids (APL) were studied in 97 patients which had ischemic stroke in young age (up to 46 years). These antibodies (Abs) were found in 25 patients (26%): Abs to cardiolipin--in 15 patients (60%), Abs to lupoid anticoagulant in 18 from 24 patients (75%), Abs to phosphatidylethanolamine--in 4 from 13 patients (31%). Disorders of cerebral circulation (DCC) usually began at the age of 14-45 years and were characterized by ischemic strokes and by transitory DCC. There was no correlation between the occlusion of extracranial arteries and their hemodynamic significant stenosis. There was occlusion of intracranial arteries in 7 from 12 patients (58%). Other risk factors of the stroke development were also found in 19 patients (76%) together with Abs to phopholipids. Other manifestations of antiphospholipid syndrome (APLS) were observed in 68% of the patients: miscarriage of pregnancy (63%), thrombosis of peripheric veins (16%), thrombocytopenia (32%), ischemic heart disease (28%). Comparison of APL+ and APL- patients revealed that transitory DCC, occlusion of intracranial arteries, intact extracranial arteries, widening or condensation of the cardial valves on echo-ECG, abortions, increase of ESR were significantly more frequently observed in the former group. For confirmation of APLS diagnosis it was necessary to study simultaneously Abs to cardiolipin and lupoid anticoagulant. Prophylaxis of repeated DCC in APLS included administration of both aspirin and anticoagulants of indirect action.

[Endothelial antibodies in Sneddon's syndrome]. / Antitela k éndoteliiu pri sindrome Sneddona.

Endothelial antibodies (EAB) were determined by enzyme immunoassay in 39 patients with Sneddon syndrome. EAB were detected in 12 patients (31%). Antibodies to phospholipids occurred more frequently in EAB-positive patients. Clinically, EAB-positive and EAB-negative patients were similar except renal syndrome which in the form of proteinuria was more frequent in EAB-positive subjects.

[The clinical importance of determining protein C and protein S in patients with nonspecific aortoarteritis]. / Klinicheskoe znachenie opredeleniia belka C i belka S u bol'nykh nespetsificheskim aortoarteriitom.

Solid-phase enzyme immunoassay estimated S and C protein levels in 10 patients with nonspecific aortic arteritis (NAA). Lowered concentrations of total protein S (< 70%) occurred in 8 (80%) of 10 NAA patients, in 3 of them protein C was also low. Isolated reduction of protein C was encountered only in one patient. Four patients (44%) of 9 had antibodies to phospholipids, as a rule, in low concentrations. 3 of them had low total protein S concentrations against normal C protein. 4 patients (40%) showed elevated concentrations of WF antigen concentrations. No relationship was noted between a fall in total protein S, C concentrations and clinical presentation of NAA, the disease activity, presence of antibodies to neutrophil cytoplasm and antibodies to endothelial cells. Thus, a reduction in the levels of total protein S in NAA patients is induced by endothelial dysfunction unrelated to production of antibodies to phospholipids, neutrophil cytoplasm and vascular endothelium.

[Antiendothelial antibodies in systemic scleroderma and Raynaud's disease]. / Antiéndotelial'nye antitela pri sistemnoi sklerodermii i bolezni Reino.

Using ELISA on fixed endothelial hybridoma (EAhy.926) cells we investigated the occurrence of antiendothelial antibodies (AEA) in the sera from patients with scleroderma systematica (SS) (n = 70) and Raynaud's disease (RD) (n = 19). The mean IgG and IgA-AEA levels were significantly higher in the SS patients than RD patients (p < 0.001) and controls (p < 0.001). We have detected circulating IgG-AEA in 64.2% of patients with SS, 35.2% of SS sera were positive for IgA-AEA. In patients with RD, the frequency of AEA corresponded to that of the random population sample. We have found a high incidence of Raynaud's phenomenon, myositis, telangiectasia and marked digital ischaemia (digital ischemic pulp ulcers, digital scars, osteolysis and autoamputation) among AEA positive patients with SS. AEA-positive patients were characterized by high extent and severity of Raynaud's phenomenon and higher average nailfold capillary microscopy scores. No correlations were found between AEA and different clinical or laboratory parameters, including the type of scleroderma (diffuse and limited), the presence of anti-Scl-7O and anticentromere antibodies and the clinical features of SS (lungs, kidneys and heart involvement, esophageal dysfunction, calcinosis, Sjogren's syndrome). There was no significant correlation between the AEA level and patient age, extent of skin involvement (skin score). Thus, in SS, AEA is associated with a peripheral vasculopathy and represent a useful marker for the diagnosis of endothelial dysfunction.

[The cellular immunity indices in diabetic nephropathy]. / Pokazateli kletochnogo immuniteta pri diabeticheskoi nefropatii.

A study was made of the content of lymphocyte subpopulations and activation marker expression on peripheral blood mononuclear cells. There were 15 patients with diabetic nephropathy (DN) in the pre-nephrotic stage and 19 patients with lingering diabetes mellitus (DM) not complicated by DN. Indirect immunofluorescence and monoclonal antibodies to leukocytic differentiated antigens CD3, CD4, CD8, CD22, CD25, CD71 and HLA-DR were used. Radioimmunoassay was employed simultaneously to measure the content of neopterin (a marker of cellular immunity activation) in the serum. It has been demonstrated that the pre-nephrotic stage of DN is marked by the normal content of the main subpopulations of peripheral lymphocytes (CD3, CD4, CD8 and CD22-positive). At the same time DN is associated with hyper-expression of activation markers (CD25, HLA-DR) on peripheral blood mononuclear cells and with an increase of serum neopterin concentration. The pathogenetic role of activated lymphocytes in DN may be related to the production by them of endoglycosidase, an enzyme splitting heparan sulfate of the subendothelial basal membranes of the glomeruli, thereby interfering with the negative charge of the glomerular filter and the local anticoagulation potential.

[Study of lymphocyte subpopulations and the expression of activation markers in diabetes mellitus types 1 and 2]. / Izuchenie subpopuliatsii limfotsitov i ékspressii markerov aktivatsii pri sakharnom diabete 1-go i 2-go tipov.

Diabetic patients with the disease duration less than 1 year (group 1 eight patients with diabetes mellitus type I and group 2 seven patients with diabetes mellitus type II) and 8 healthy donors were examined for subpopulations of lymphocytes (CD 3-, CD 4-, CD 8-, CD 20-positive cells, CD4/CD8), expression of activation markers on peripheral blood mononuclears investigated with monoclonal antibodies of BMA and OKT series, and serum neopterin concentration. Group I patients had low CD4/CD8 and increased number of CD 8 cells, 1a/DR-positive lymphocytes (28.6 +/- 7%), OKT9-positive lymphocytes (8.0 +/- 4.7%), activated neopterin synthesis registered neither in group 2 patients nor donors. The number of CD 3 and CD 4 cells was similar in the diabetics and donors. B-lymphocyte level in group 1 patients was on the decrease. Unbalance in lymphocyte subpopulations, increased expression of activation markers and of serum neopterin can be noted in viral infection reflecting impairment of immunoregulating mechanisms in diabetes mellitus type I.

[The functional activity and count of the natural killer cells in patients with recently diagnosed diabetes mellitus types I and II]. / Izuchenie funktsional'noi aktivnosti i kolichestva estestvennykh kletok-killerov u bol'nykh s nedavno voznikshim sakharnym diabetom I i II tipa.

Eight patients with type I diabetes mellitus (D-I), seven patients with type II diabetes mellitus (D-11) and 8 healthy donors were examined. The disease standing did not exceed 1 year since the moment of the diagnosis establishment. The patients with D-I manifested activation of natural killers (NK) as compared to their activity in the donors and patients with D-II (76.05 +/- 6.5%, 52.33 +/- 9.55% and 55.39 +/- 10.63%, respectively, p less than 0.01) in the presence of the attenuated response of NK to interleukin-2 and alpha-interferon, determined by NK prestimulation. The amount of NK (CD16-positive) in D-I was significantly less than in the donors and patients with D-II. The high activity of NK in D-I correlated with an increase of receptor expression for transferrin on the mononuclear cells of peripheral blood. At the same time 5 out of the 8 patients with D-I and 2 patients with D-II out of the 7 demonstrated the rise of serum alpha-interferon (in the titer 1:40 and over). Activation of NK and the rise of serum interferon may be due to viral etiology of the disease and may play a role in the autoimmune process in patients suffering from D-I.