[Results of leflunomide treatment of psoriatic arthritis].

AIM: To study efficacy and tolerance of leflunomide (LF) in patients with polyarticular psoriatic arthritis (PsA). MATERIAL AND METHODS: The analysis was made in 58 patients: 35 (60%) females, 23 (40%) males. Mean age of the patients was 44.9 +/- 10.8 years, PsA duration--9.7 +/- 7.5 years. LF was given by a standard scheme: 100 mg/day for 3 days then 20 mg/day for 6 months. PsA activity was assessed by the number of painful and inflamed joints, pain intensity, VAS, Likert quastionnaire data. Functional status of the patients was estimated according to Health Assessment Questionnaire. Skin syndrome was rated by pruritus scale, 5-score Likert scale and PASI (psoriasis Area and Severity Index). PASI was applied in patients with affected area 3% at least. Quality of life was assessed by Dermatology Life Quality Index. Basic criterion of the treatment efficacy was response by PsARC (Psoriatic Arthritis Response Criteria). The additional evaluation was made of the number of patients with improvement by criteria ACR 20, ACR 50 and ACR 75 as well as those with 50 and 75% response by PASI (PASI 50 and PASI 75). RESULTS: To the end of the treatment the number of painful and inflamed joints decreased significantly (p < 0.001) as well as pain, VAS and Likert scores. To the treatment month 6 HAQ index diminished by 36%. According to PsARC, of 58 patients 36 (62%) patients responded. Improvement by ACR 20 was observed in 34 (59%) of 58 patients. PASI changes were not significant (p = 0. 144). DLQI diminished by 36% (p = 0.028). As shown by acute phase indices, LF had no effect on ESR (p = 0.45). CRP fell significantly to treatment month 3 (p < or = 0.001) and further changes were insignificant. LF tolerance was satisfactory. Ten patients (17%) withdrew because of side effects which were standard. Severe myelo- and hepatotoxicity were absent. CONCLUSION: LF is highly effective in therapy of polyarticular PsA and has satisfactory tolerance. Perspectives of further use of LF in combined treatment of PsA are associated with its potential to inhibit the disease progression.

[Diagnostic implications of detecting antibodies to angiotensin-converting enzyme and its substrates]. / Diagnosticheskaia vozmozhnost' opredeleniia antitel k angiotenzinprevrashchaiushchemu fermentu i ego substratam.

The results of the analysis of diagnostic significance of examination of natural antibodies (Nab) to agiotensin-converting enzyme (ACE) and its substrates in the serum of hypertensive patients indicate that concentration of Nab to ACE differ from this mean concentration in donors. An elevated level of Nab to ACE may be considered as a compensatory reaction to increased content of the enzyme in vascular endothelium and blood flow. The same patients were examined for antibodies to peptide angiotensin II (AT-II). Enzyme immunoassay has shown that a significantly elevated level of antibodies to AT-II was only in 5 examinees. The same patients had also high Nab to ACE. The study of a group of ischemic heart disease patients with adverse effects attributed to bronchial affection treated with enalapril and diroton (ACE inhibitors) demonstrates that deterioration of cough and external respiration function is not related to exacerbation of existing chronic pulmonary inflammation. None of the patients had elevated body temperature or inflammatory changes in the blood, other signs of inflammation. Enzyme immunoassay also proved that the initial level of Nab equaled mean value for donors or was insignificantly lower. Blood serum patients with side effects contained a significantly (p < 0.02) elevated quantities of Nab to bradikinin vs initial values. Thus, the proposed method of solid phase enzyme immunoassay quantifies Nab to ACE and its substrates in the patients.

[Use of monoclonal antibodies to tumor necrosis factor (remicade) in rheumatoid arthritis: preliminary results]. / Primenenie monoklonal'nykh antitel k faktoru nekroza opukholi (remikeid) pri revmatoidnom artrite: predvaritel'nye rezul'taty.

AIM: To study effectiveness and tolerance of monoclonal antibodies to tumor necrosis factor (the drug remicade) in patients with rheumatoid arthritis (RA). MATERIAL AND METHODS: Remicade treatment results are considered for 25 RA patients receiving methotrexate the activity of which was inadequate for these patients. Remicade was infused intravenously in a dose 200 mg 4 times for 22 weeks. RESULTS: Remicade produced positive clinical and laboratory effects as early as the first infusion. The response was observed during 22 weeks of the treatment in 17 of 25 patients. Remicade tolerance was good. One patient failed the treatment because of development of collapse. CONCLUSION: Pilot results of remicade trial point to its high therapeutic potential and perspectives in rheumatology.

[Autoantibodies to vasoactive peptides and angiotensin converting enzyme in patients with systemic diseases of the connective tissue]. / Autoantitela k vazoaktivnym peptidam in angiotenzinprevrashchaiushchemu fermentu u bol'nykh s sistemnymi zabolevaniiami soedinitel'noi tkani.

AIM: To estimate the level of natural autoantibodies (NAAb) to angiotensin-converting enzyme (ACE) and endogenic mediators affecting vascular tone (bradykinin--BK, angiotensin II--AII, vasopressin--VP) as well as the activity of serum ACE in patients with systemic diseases of the connective tissue. MATERIAL AND METHODS: Levels of NAAb were measured by enzyme immunoassay in sera from 30 patients with SLE, 19 patients with rheumatoid arthritis (RA) and 36 patients with scleroderma systematica (SS). Serum from donors served control. IgM NAAb to ACE were measured by a new technique. Serum ACE activity was determined by the initial velocity of hydrolysis reaction using spectrofluometry. RESULTS: IgM NAAb were detected in the sera of both patients and donors. SS patients had the level of NAAb to ACE in diffuse form significantly higher than in limited (p < 0.05). In SLE and SS patients ACE activity was significantly lower (p < 0.05) than in healthy subjects and RA patients. Levels of NAAb to BK was significantly elevated (p < 0.01) in patients with SLE and RA vs donors while to AII in SS patients it was lowered (p < 0.001). Patients with diffuse SS had NAAb to BK higher than patients with SS limited form (p < 0.01). In SLE the lowest levels of NAAb to all the mediators studied were observed in patients with nephritis, for NAAb to VP the differences were significant (p < 0.05). In patients with urinary syndrome concentration of NAAb to BK was significantly higher (p < 0.01), differences between their levels in patients with nephritis and urinary syndrome were also significant (p < 0.05). CONCLUSION: Further studies are needed for specification of physiological or pathological role of NAAb to endogenic mediators.

[Interferon therapy effects on activation of T-lymphocytes in patients with systemic lupus erythematosus]. / Vliianie terapii interferonom na aktivatsiiu T-limfotsitov bol'nykh sistemnoi krasnoi volchankoi.

AIM: To elucidate the effects of combined therapy with glucocorticosteroids (GCS) and recombinant human interferon alpha or gamma (IFN) on proliferative responses of T-lymphocytes activated by various surface molecules (CD3 and CD2) in patients with SLE. MATERIALS AND METHODS: A 3-month trial entered 3 groups 15 patients each with verified SLE by APA criteria (1982). Patients of group 1, 2 and 3 received IFN-alpha (realdiron, Biofa, Lithuania) in a single dose 3 million IU i.m., IFN-gamma (inflagen, Biofa, Lithuania) in a single dose 3 million IU i.m. and cyclophosphamide in a dose 200 mg i.m. once a week, respectively. T-lymphocyte proliferative response was assessed to stimuli of two types: CD3-dependent (classic activation) and CD2-dependent (alternative activation). The analysis was made by inclusion of 3H-thymidine after 72-hour incubation of peripheral blood mononuclear cells with various stimuli. The response was assessed before the treatment, on the treatment day 20 and after the treatment. The blood from 27 donors was also examined. Flow cytometry estimated the percentage of the cells expressing molecules CD3, CD4, CD8. RESULTS: The effect is found of alpha and gamma INF on functional capacity of T-lymphocytes and on the number of cells expressing surface molecules CD3 and CD4. Realdiron produced two-phase reaction to a proliferative response to mitogenic stimuli by CD3-dependent activation pathway: the initial rise then lowering. CD2-dependent way of T-cell activation is associated with weakening of responses to all combinations of stimuli with participation of autologous red cells. This group of patients to the end of the therapy exhibited a significant decrease in the number of cells expressing CD3 and CD4 (p < 0.05 and p < 0.001, respectively). Inflagen enhanced CD3-dependent activation of T cells and normalized the response to all types of the alternative stimuli. This group demonstrated an increase in the number of cells expressing CD3 and CD4 (p < 0.01 and p < 0.05, respectively). The changes in the number of CD8+ cells in both the groups were statistically insignificant. The controls had T-cell responses reduced by both activation pathways. CONCLUSION: Preparations of both alpha and gamma interferon have a multidirectional influence on functional potential and phenotype of T-lymphocytes of SLE patients.

[The classical and alternative pathways of T-lymphocyte activation in patients with systemic lupus erythematosus]. / Sostoianie klassicheskogo i al'ternativnogo putei aktivatsii T-limfotsitov u bol'nykh sistemnoi krasnoi volchanki.

AIM: To study activation of T-lymphocytes by the CD3 (antigen-dependent) and CD2 (non-antigen-dependent) routes in patients with systemic lupus erythematosus (SLE). MATERIALS AND METHODS: Peripheral blood mononuclears were studied in 66 patients with SLE and 27 donors. Proliferative response to activation by anti-CD3, anti-CD3+ phorbol-12-myristate-13-acetate (PMA), phytohemagglutinin (PHA), and autologous erythrocytes in combinations with PMA and recombinant interleukin-2 (rIL-2) was assessed. RESULTS: T-cell proliferation was at least two times increased under the effect of CD3 in 40.9% patients and in 100% normal subjects. Stimulation with CD3 antibodies in combination with PMA leveled the differences due to boosting of T-cell response in SLE patients. PMA alone caused mononuclear proliferation in 25% patients with SLE but not in normal subjects. Decreased response of T-cells to adhesive stimulus (autologous erythrocytes + PMA) in SLE patients was leveled by rIL-2. CONCLUSION: The proliferative response of T-lymphocytes is decreased upon stimulation with CD3 and CD2 and in some patients increased by PMA in submitogenic doses, added alone or in combination with anti-CD3.

[Immunoenzyme assay for detection of natural antibodies against vasopressin in systemic lupus erythematosus]. / Vyiavlenie estestvennykh antitel protiv vazopressina pri sistemnoi krasnoi volchanke immunofermentnym metodom.

A solid-phase enzyme immunoassay procedure for detecting natural antibodies to vasopressin (VP) is developed. For this purpose, a VP antigen is synthesized on polymer matrix. Optimal conditions of enzyme immunoassay for detecting antibodies to this antigen in the sera of donors and patients with systemic lupus erythematosus (SLE) are selected. The level of anti-VP antibodies is constant in donors and shifted in SLE patients. Changes in the level of natural antibodies to VP correlate with immunochemical parameters.

[Detection of rheumatoid factor in the blood of patients by latex agglutination]. / Opredelenie revmatoidnogo faktora v syvorotke krovi bol'nykh metodom lateksnoi aggliutinatsii.

A highly effective rapid method is developed for detecting the rheumatoid factor in human serum. Polystyrene suspension-based latex conjugate is synthesized, representing a styrene and methacrylic acid copolymer. The immunospecific reagent is human IgG. The resultant latex conjugate can be used in practical medicine for analysis of the rheumatoid factor.

The resistance of activated T-cells from SLE patients to apoptosis induced by human thymic stromal cells.

In this paper we show the differential sensitivity of phytohemagglutinine (PHA) activated T-cells from healthy donors or patients with systemic lupus erythematosus (SLE) to apoptosis induced by human thymic stromal cell line of epithelial origin. T-cells from SLE patients were mainly resistant to the apoptotic action of the stromal cells, while normal T-lymphocytes readily died via apoptosis. Gel electrophoresis revealed a DNA fragmentation pattern characteristic of apoptosis after 18 h of coculture. The simultaneous measurement of [3H]-thymidine uptake showed that the proliferative response of T-cells from SLE patients was significantly decreased compared to their normal counterparts. Such difference may account for the distinct result of interactions between the stromal and lymphoid cells, leading to the subsequent survival of T-lymphocytes from SLE patients. Nevertheless pretreatment of normal activated T-lymphocytes with anti-Fas mAbs, which have the capacity to substantially inhibit signaling through this receptor resulted in abolition of this form of programmed cell death. Thus, the precise role of Fas receptor and its ligand in this in vitro test system needs further investigation.