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One major problem in the management of steroid refractory attacks of patients with inflammatory bowel disease (IBD) is the establishment of a rapidly acting immunosuppressive regimen. Based on its well known efficacy in systemic vasculitis, intravenous cyclophosphamide pulse therapy was used in refractory IBD patients to evaluate both its efficacy and safety.Between December 1998 and May 2001, seven patients (Crohn's disease, n=5; indeterminate colitis, n=1) with severe steroid refractory IBD (Crohn's disease activity index (CDAI) 264-479 points) received 4-6 cycles of monthly treatment with intravenous cyclophosphamide (750 mg) in a prospective uncontrolled pilot study.All patients improved after two intravenous pulses of cyclophosphamide and six of seven patients achieved complete remission (CDAI150 points). One patient with Crohn's disease of the small and large bowel showed an impressive clinical response but did not enter into remission. Tapering to low dose steroids was possible in all responders. Remission was maintained in all patients for 18 months (median) but required a second course of intravenous pulse cyclophosphamide in one patient. The drug was well tolerated except for two episodes of candida oesophagitis.Intravenous pulse cyclophosphamide may be a safe and effective treatment in patients with severe IBD unresponsive to steroid treatment and merits evaluation in a controlled trial.

Two-hundred ninety five patients with the antiphospholipid syndrome (APS) were studied for the presence of antibodies against six anti-beta2GPI-related peptides Abs. The prevalence of a wide spectrum of clinical and laboratory parameters of APS was evaluated in all patients, and correlated with the presence of each anti-beta2GPI peptide antibody. The rates of the various antipeptides Abs ranged from 18.0 to 63.7%. Altogether, 87.1% of the patients had antibody reactivity against at least one of the six beta2GPI-related peptides. A high degree of simultaneous reactivity against several beta2GPI-peptides was found. Positive and negative correlations were found between several antipeptides Abs and the rates of thrombosis and fetal loss. Our results point to a heterogeneous activity of antiphospholipid Abs in APS patients, directed, often concurrently, against various epitopes of the beta2GPI molecule. Evaluation of APS patients for the presence of specific antipeptides Abs may be of a value in predicting the risk for future thrombotic and obstetrical complication, as well as for specific therapeutic purposes.

BIBFORM034025-újratöltve

The bactericidal effect of 25 serum samples from 23 patients with chronic lymphocytic leukaemia (CLL) against the Salmonella minnesota S form and Re mutant has been studied. No killing of the S form was observed in any of the sera tested, whereas a normal bactericidal effect was found against the Re mutant (group 1) in 17/25 sera of CLL patients. By contrast, in 8 serum samples from 6 CLL patients no killing or a markedly delayed killing of the Re strain was observed (group 2). Significant differences in the complement levels were found between the sera of group 1 and group 2. In group 1 mostly normal or elevated complement levels were observed, while in group 2 levels of C4 and C2 were found to be strongly decreased. A significant correlation was found between the bactericidal effect on the one hand and the C4 and C2 levels on the other.

Sera from patients were tested for the presence of soluble immune complexes (IC) by a method based on the observation that IC inhibit uptake of aggregated IgG by the Fc receptors of macrophages. From the saturation curve of macrophages with 125I-labelled aggregates the optimal inhibitory effect of a measured amount of IC was determined. This radioassay is highly sensitive, being capable of detecting 20 ng of IC, is reproducible and covers a wide range of measurement (20-2000 ng).

The capacity was studied of bovine serum albumin (BSA) rabbit anti-BSA and ovalbumin (OA) rabbit anti-OA immune complexes of different composition to inhibit the Fc receptor-dependent adherence and phagocytosis of sensitized sheep red blood cells by human monocytes. Parallel experiments were performed on the ability of the immune but complement-reacted complexes to inhibit the C3 receptor-dependent phagocytosis of C3-coated yeast particles. The extent of inhibition of both the Fc and C3 receptor-dependent phagocytosis was proportional to the antibody avidity of the complex used. Immune complexes made at equivalence and at moderate antibody excess markedly inhibited both types of phagocytosis, whereas those made at moderate antigen excess had only a weak inhibitory effect. These findings can be explained by the correlation between the Fc receptor-binding and complement-activating capacities of immune complexes of different composition. An alternative explanation, however, is also discussed.

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.

The adult onset Still disease is a systemic disease of an unknown etiology. As a separate entity, it was described firstly in 1971. The diagnosis is problematic and based upon special criteria. In this study, we present the cases of two patients with adult onset Still's disease, causing several serious differential-diagnostic problems. In the beginning of the disease a high, remittent-intermittent fever was present which reacted well to salycilates. Almost simultaneously, a characteristic, confluent, no itching rash appeared on the trunk and limbs. Pain of little joints of the hands was an early symptom of the disease in both of the cases. Before the final diagnosis, the possibility of any infectious diseases, haematologic malignancies or other autoimmune disease had to be excluded. The aim of this work was to show an overall, up-to-date picture of the disease based on two typical cases.

Introduction: T cell depletion is a widely used therapeutic approach in transplanted patients to suppress rejection. These therapeutic antibodies never reach complete T cell elimination. Several studies with mice and humans showed that T cells with memory-like phenotype are relatively resistant to antibody-mediated T-cell depletion. In the absence of data on the possible survival niches in the peripheral lymphoid tissues, we investigated where the resistant cells are spared from depletion during the early phase of treatment. Materials and Methods: We used IBL-1 rat monoclonal antibody against Thy-1/CD90 antigen in wild-type (BALB/c and [B6xBALB/c] F1) and transgenic mouse strains (c3-/-, AND TcR Tg). The depletion efficiency was monitored by the flow cytometric and immunofluorescent microscopic assessment of peripheral lymphoid tissues using CD62L, CD44, CD4, CD8, Foxp3 and PD1 markers. In vitro T-cell activation was monitored using Ca-assay and phosphotyrosine (PY) immunoblots. Results: In F1 mice in the blood and the spleen T-cells were almost completely eliminated, while in the peripheral lymph node (pLN) one third of the T-cells survived. In pLN samples we found significant (p=0, 009) increase of central memory (CD62L+/CD44hi) T cells. In AND mice with a large increase in memory T cells, 24 to 36 hours after the application of IBL-1 mAb we did not find any T-cell depletion in pLN’s compared to the spleen and blood. In contrast to F1 mice, both central and effector memory (CD62L-/CD44hi) T cells showed significant reduction. In BALB/c mice an extensive drop of naïve T-cell frequency and enrichment of memory cell type was observed in all tissue samples. However, even in BALB/c mice pLN T cells showed significant resistance when compared with blood and spleen. In mice lacking complement factor C3 the degree of lymphocyte depletion was the same as in wild-type BALB/c mice. Immunoflorescence on tissue sections did not reveal any alteration of specific regional tissue location of survival T-cells Also, we found no difference in the frequency of regulatory T cells (CD4+/Foxp3+) upon anti-Thy-1 treatment. In vitro exposure to IBL-1 mAb induced a low but immediate calcium influx. Preliminary Western blot analyses by anti-PY mAb in lymphocyte lysate from anti-Thy-1 mAb-treated animals did not reveal any increase in phosphotyrosine content. Conclusions: Our results showed that pLNs in mice provide a protective environment for T-cell upon treatment with depleting antibodies, irrespectively of mouse strain, but with various capacities for protection. As there are no parallel data in humans, such studies in experimental animals are likely to lend new data on the course of lymphocyte depletion and survival.