[Comparative analysis of clinical and laboratory charactiristics of antiphospholipid syndrome]. / Az antifoszfolipid-szindróma klinikai és laboratóriumi jellemzóinek összehasonlító vizsgálata.

The authors detected lupus anticoagulant and/or anticardiolipin antibodies in 1519 patients' blood samples between 1986-1999 in 3rd Department of Internal Medicine of Medical School of Debrecen. Examining only the proved thrombotic events and fetal losses as symptoms of antiphospholipid syndrome 218 patients had suffered from this syndrome. Secunder antiphospholipid syndrome was the diagnosis in case of 420 patients, the most common in Systemic Lupus Erythematosus (288 patients). In 704 antiphospholipid antibody positivity cases the diagnosis of antiphospholipid syndrome was not fulfilled. Analysing the antibodies profile of primary and secondary antiphospholipid syndrome in SLE, IgG type anticardiolipin antibody positivity was significantly higher in blood samples of SLE patients (82 patients, p < 0.01). Among thrombotic manifestations of antiphospholipid syndrome cerebrovascular thrombosis were significantly higher in patients suffering from SLE (128 patients, p < 0.04), while the occurrence of venous thrombosis, thrombosis of coronary, carotic, aorta and peripheral arteries and recurrent abortions was not significantly different in case of primary and secondary antiphospholipid syndrome. Lupus anticoagulant positivity means higher risk for venous thrombosis (94 patients, p < 0.0001), but anticardiolipin antibody positivity associated with a higher risk for thrombosis of coronary, carotic, aorta and peripheral arteries (59 patients, p < 0.00006). Comparing IgG- and IgM-type anticardiolipin antibody positivity the authors found significantly higher cerebrovascular thrombosis events in IgG-anticardiolipin group (p < 0.004). Sneddon syndrome were detected in 17 patients in the primary antiphospholipid syndrome group and in 16 cases in secundary, SLE-associated antiphospholipid syndrome group. One of the patients had died because of the Catastrophic Antiphospholipid Syndrome.

[Favorable in vitro effect of pentoxifylline on damaged lymphocyte migration in arteriosclerosis obliterans and systemic lupus erythematosus]. / Pentoxifillin (Trental) kedvezö hatása a károsodott in vitro lymphocyta migrációra arteriosclerosis obliteransban és systemás lupus erythematosusban.

Decreased blood cell--e.g. lymphocyte--motility is seen in a number of vascular and autoimmune diseases. Pentoxifylline (Pf) shows a well-known therapeutic effect in several vascular alterations by causing the redistribution of blood cell cytoskeleton and increased microcirculation. As most literary data on Pf concern red blood cells and granulocytes authors here investigated the effect of Pf on previously decreased lymphocyte migration and chemotaxis. Results of in vitro studies suggest that Pf enhances impaired lymphocyte motility in obliterative arteriosclerosis and systemic lupus erythematosus and thus may also be introduced in the treatment of polysystemic autoimmune diseases.

Effect of pentoxifylline on decreased in vitro mononuclear leucocyte chemotaxis in vascular and polysystemic autoimmune diseases.

Impaired mononuclear leucocyte (MNL) motility can be found both in vascular and autoimmune diseases. Pentoxifylline (PTX) has a well-known therapeutic effect in vascular diseases, which is based on the rearrangement of blood cell cytoskeleton and thus increased microcirculatory flow. Most data on PTX concern red blood cells and granulocytes so now the effect of PTX on previously decreased MNL migration and chemotaxis was investigated in vitro. The results of MNL chemotaxis studies described here suggest that this drug enhances impaired MNL motility in obliterative atherosclerosis and systemic lupus erythematosus and thus may also be introduced in the treatment of certain polysystemic autoimmune diseases with decreased in vitro MNL chemotaxis.

[Reflections on non-differentiated collagenosis or non-differentiated autoimmune syndrome]. / Gondolatok a Nem Differenciált Collagenosisról (NDC), illetve a Nem Differenciált Autoimmun Syndromáról (NAS).

The authors review the Non-Differentiated Collagenosis (NDC) described by Gyula Petrányi 29 years ago, and try to establish whether it is still necessary to maintain this clinical picture. Relying on data from special literature and on their own findings, the authors conclude that the maintenance of the NDC terminology is justified by the fact that poly-systemic autoimmune diseases take time to develop and that at certain stages of this development it is almost impossible to make a firm decision as to which clinical picture the process will lead to. The authors discuss the clinical and immunological features of NDC, the implications for the patients and things to be done in order to recognise the NDC disease process. They also emphasize a more frequent occurrence of the features of NDC than is generally stated, and that such patients need regular, competent and devoted medical attention.

The antigen/receptor specificity of antigranulocyte antibodies in patients with SLE.

The antigen/receptor specificity of antigranulocyte antibodies (AGAs) detected in the sera of patients with systemic lupus erythematosus (SLE) was investigated by inhibitory immunofluorescence test and Western immunoblotting technique. The interactions of AGAs with antigens of intact normal granulocytes were determined by inhibiting the binding of different myeloid monoclonal antibodies (mAbs). Seven of the studied 12 sera revealed binding to CD15 (X hapten) and/or to CD16 (FcR1o). The specificity investigation of AGAs was completed with Western immunoblotting technique. The binding of AGAs to bands with Mr of about 50-60 kDa and at 30 kDa on unstimulated granulocyte plasma membrane preparation could be demonstrated from 4 out of 6 AGA positive SLE sera. The cause of the disappearance of bands on the phorbol-myristate-acetate (PMA) activated membrane except those of the 50-60 kDa bands is still to be discovered.

Granulocyte-rosette assay for detection of anti-lymphocyte antibodies.

It is well known that the serum of SLE patients contain anti-lymphocyte antibodies (ALA). In this paper we present a new rosette-forming assay for investigation of ALA. The method is based on the first step of antibody dependent cellular cytotoxicity (ADCC): the adherence of Fc-receptor bearing effector cells to the lymphocytes coated by antibodies. SLE serum samples were tested simultaneously by the new method (the rosette-test, RT) and the microcytotoxicity test (MCT) based on the complement mediated lysis. The results obtained by use of MCT and RT showed that the latter is suitable for investigation of ALA, indeed its diagnostic parameters are better than those of MCT. Moreover these results suggest that the two tests may differ in the antibody class detected. The new method is simple, time saving and demands no 51Cr-isotope as other ADCC tests do.

Defective immune complex degradation by monocytes in patients with systemic lupus erythematosus.

The binding of 125I-labelled anti-bovine serum albumin (BSA)-BSA immune complexes (IC), giving a final molar antibody to antigen ratio of 1:1, to monocytes isolated from 18 patients with systemic lupus erythematosus (SLE) and from 10 normal healthy donors was quantitatively investigated. The degradation of the bound IC by the same monocytes was kinetically determined at the same time. The assays were performed on monocyte monolayers. Scatchard plots at 4 degrees C demonstrated that monocytes from patients with active SLE expressed a mean Fc gamma receptor (FcR) number that was 22% higher than that of the controls, although this did not reach statistical significance. The FcR number of normal monocytes and the degradation rate of anti-BSA-BSA complexes by the same cells showed a positive correlation. At the same time, the digestion of anti-BSA-BSA complexes by monocytes of SLE patients with active disease was prolonged, despite their enhanced FcR-ligand binding. The dissociation of FcR-ligand binding and FcR-mediated degradation suggests that the IC degradation is controlled by altered biochemical mechanisms in the monocytes of SLE patients.

Heterogeneity of systemic lupus erythematosus elucidated by cluster analysis. The influence of HLA.

For 75 patients with systemic lupus erythematosus (SLE), 39 laboratory and clinical characteristics, including HLA-A, B, C and DR typing, were analysed using a cluster analysis technique. Three groups were identified. Group I (46 patients) was characterized by infrequently severe disease, good response to therapy and infrequent multisystem involvement. Group II (24 patients) was characterized by a severe course of disease (although the tendency to remit after therapy was not unusual), and frequently, renal involvement and pericarditis. Group III (5 patients) was characterized by more severe renal disease. Of the 75 patients studied, 38.7% possessed HLA-DR3, compared to 17.4% of controls. Group I patients did not differ from controls but 80% of Group II patients and 4/5 Group III patients had DR3. Cluster analysis identifies subsets of SLE patients who show marked differences in disease course and severity, correlated with possession of the HLA B8, DR3 phenotype.

Lymphocyte markers in patients with progressive systemic sclerosis.

18 patients with progressive systemic sclerosis were investigated. An absolute lymphopenia and a decrease in the number of E-rosettes and early E-rosette forming cells were found. The number of T gamma cells was reduced as compared to the control values. No diminution was found in the number of histamine receptor bearing cells but the number of T lymphocytes capable of recognizing autologous red blood cells was considerably decreased. The number and the ratio of these T cell subpopulations remained relatively stable even after 6 months in the patients with progressive systemic sclerosis. No individual correlation was found between the clinical findings and the ratio of T cell subpopulations.

Inhibitory effect of monocyte reactive antibodies on monocyte chemotaxis in systemic lupus erythematosus.

Presence of different types of autoantibodies is a basic feature of systemic lupus erythematosus (SLE). Though monocytes, macrophages play an important role in cellular immunity, autoantibodies against monocytes have not been sufficiently studied. The authors used automatic fluorochromatic assay to detect monocyte reactive autoantibodies in the sera of SLE patients. Of SLE 35.5% sera showed complement-mediated monocytotoxic activity against healthy monocytes. Monocyte reactive SLE sera as well as monoclonal antibodies against human monocytes inhibited chemotaxis of control monocytes. The results suggest that monocyte reactive autoantibodies may play a role in the decreased monocyte number and defective monocyte functions observed in SLE.

The effect of sera of patients with systemic lupus erythematosus on artificial immune complexes.

The solubilization of artificial immune complexes mediated by complements has been well-known since 1975. It is known that the process is bound to the integrity of the alternative complement pathway. The phenomenon of solubilization can be used in the investigation of the function of the complement system. We have studied the solubilization of artificial complexes containing BSA and 125I labelled anti-BSA on the effect of sera of healthy subjects and those of patients suffering from SLE. We have observed that the solubilization capacity of SLE sera is significantly lower than that of healthy persons. The decrease is the most distinct at the time of the activity of the disease.

Serum IgE level in systemic lupus erythematosus.

The serum total-IgE level has been studied in systemic lupus erythematosus (SLE), in order to obtain data concerning the significance of IgE antibodies in the appearance of SLE symptoms. In most patients the serum IgE content was significantly higher in the active stage of the disease than during remission. The findings indicated a specific statistical distribution due to the multiple factors influencing IgE production and so an augmented IgE level cannot be regarded as a reliable feature of SLE activation.

Subset specificity of lupus antilymphocyte antibodies studied by two-colour microfluorimetry.

Subset specific lymphocytotoxic activity of lupus sera was studied by a combination of selective immunofluorescence labelling and complement-mediated lysis. Most frequently death of B cells was detected. Many of the sera caused lysis of T lymphocytes; selective cytotoxicity against suppressor T cells could be observed less frequently. All the anti-T4, anti-T8 and anti-B lymphocyte antibodies proved to be cold reactive.

Cellular DNA content of T helper, T suppressor and B lymphocytes in SLE.

The ratio of in vivo activated T helper, T suppressor and B cells in the blood of patients with SLE has been studied through simultaneous subset specific immunofluorescence labelling and the analysis of cellular DNA content with the help of flow fluorimetry. In the active stage of the disease an increase was observed in the proportion of proliferating cells either among the T helper cells or the B cells. Occasionally, however, the rate of proliferation in both subsets grew at the same time. Cases with a high number of activated B cells have proved to be more serious. The percentage of the T suppressor cells in the S-G2-M phase of the cell cycle increased moderately in both the active and the inactive stages of the disease. Our results are also discussed in relation to the pathogenetic mechanism of SLE.

Effects of immune complexes from SLE patients on human monocyte locomotion and Fc receptor function.

The effect of immune complexes (IC) isolated from systemic lupus erythematosus (SLE) sera with polyethylene glycol and gel filtration on the chemotaxis and Fc receptor function of healthy monocytes was examined. Even at a low protein concentration (1 microgram/ml = 1 mg/l) ICs inhibit monocyte chemotaxis. ICs from patients with SLE nephritis are more inhibitory than ICs from patients without renal disease. The inhibitory effects of ICs on monocyte chemotaxis and Fc receptor activity are similar, suggesting a relationship between the chemotactic and Fc receptor function of monocytes. Analysis of the ICs by enzyme-linked immunoassay showed no correlation between the quantity of IgG, C3, and anti-DNA in the IC samples and their effects on monocyte function.

Stimulating effect of tuftsin and its analogues on the defective monocyte chemotaxis in systemic lupus erythematosus.

Monocytes and macrophages are engaged at various levels of cellular immune reactivity. In addition to their function in the defensive mechanism directed at infective agents, they also play a basic role in immune complex elimination and antigen handling. Previous experiments revealed that systemic lupus erythematosus (SLE), the main representative of the autoimmune diseases, is associated with impaired monocyte chemotaxis. The endogenous basic tetrapeptide tuftsin and 6 of its analogues were examined in vitro for their stimulating capacity on the chemotactic responsiveness of monocytes derived from patients with SLE. The monocyte migration assay was carried out by a modified Boyden technique and quantified by the leading front distance method and by counting the total distance covered by the monocyte locomotion. Tuftsin and 3 of its analogues significantly increased the defective chemotaxis in SLE. The tetrapeptides effective on chemotaxis also stimulated random migration and phagocytosis of the monocytes, albeit to a lesser extent. Structure-activity relationships, as well as the influence of the clinical stage of the disease were also examined. Experimental evidence leads to a favourable prediction for the immunotherapeutic value of these oligopeptides for the control of infections and the progression of the disease in patients with systemic lupus erythematosus.

Autologous rosette-forming capacity of T-lymphocytes in Hodgkin's disease.

Distribution of the T-lymphocyte subpopulation capable of binding own erythrocytes was examined in patients with Hodgkin's (H) disease. Parallel with the autologous rosette-forming cells (Tar-cells) the absolute lymphocyte count and the proportion of sheep-E-rosette forming T-cells were studied in various stages and histological types of H-disease. A considerable increase in the proportion of Tar-cells was found in untreated or recurrent H-disease, whereas in the periods of remission resulting from therapy no distinct differences between these figures and the mean values of the controls were demonstrable. In the generalized stage of the disease as well as in its mixed-cell and lymphocyte depletion types of poor prognosis, the proportion of Tar-cells was increased. The absolute lymphocyte count and the proportion of T-cells showed a significant fall with the increase of Tar-cells. It is assumed on the grounds of the functional properties of T-cells that the increase in the proportion of Tar-cells in H-disease may be interpreted as a sign of suppressor hyperactivity.

Signals of monocyte activation in patients with SLE.

The Fc receptor mediated reaction, the beta-glucuronidase and the lactic dehydrogenase activities of monocytes and the serum lysozyme level were tested together with the circulating immune complex content of patients with systemic lupus erythematosus. Simultaneously with the increasing FC receptor-mediated reaction and the elevated enzyme activities of patient monocytes, the secretion of lysozyme and the immune complex content of the sera were higher than those of the controls. A positive correlation was demonstrated between the Fc receptor-mediated reaction, the beta-glucuronidase activity, the lysozyme secretion and the immune complex content of the sera. Thus, the monocytes of patients appeared to be activated by the circulating immune complexes.