Behcet's disease is a multisystem disease in which there is evidence of immunological dysregulation. It has been proposed that γ/δ T cells are involved in its pathogenesis. The aim of the present study was to assess the capacity of γ/δ T cells with phenotype Vγ9/Vδ2, from a group of Italian patients with Behcet's disease, to proliferate in the presence of various phosphoantigens and to express tumour necrosis factor (TNF) and IL-12 receptors. Twenty-five patients and 45 healthy individuals were studied. Vγ9/Vδ2 T cells were analyzed by fluorescence activated cell sorting, utilizing specific monoclonal antibodies. For the expansion of Vγ9/Vδ2 T cells, lymphocytes were cultured in the presenc…

One year study of efficacy and safety of infliximab in the treatment of patients with ocular and neurological Behçet's disease refractory to standard immunosuppressive drugs

Abstract The aim of the study was to assess the long-term efficacy and safety of Infliximab therapy in the treatment of patients with Behçet’s disease refractory to standard immunosuppressive agents. Twenty-one patients that did not respond to corticosteroids and to at least one immunosuppressant (cyclosporin, methotrexate, azathioprine, cyclophosphamide) for the presence of ocular and/or CNS involvement were enrolled. Eighteen patients completed the study up to 54 weeks. Stable doses of prednisone (<10 mg/day) were permitted, immunosuppressants were discontinued at least 4 weeks prior baseline visit. The patients received three infusions of 5 mg/kg Infliximab (at weeks 0, 2 and 6) and then…

Phenotype and functional changes of Vgamma9/Vdelta2 T lymphocytes in Behçet's disease and the effect of infliximab on Vgamma9/Vdelta2 T cell expansion, activation and cytotoxicity

INTRODUCTION: Infliximab is a chimeric monoclonal antibody against tumor necrosis factor alpha (TNF-alpha) that has been introduced recently for Behçet's disease (BD) patients who were resistant to standard treatment. The aim of this study was to analyse the functional changes of Vgamma9/Vdelta2 T lymphocytes in both active and inactive disease and the effect of infliximab on Vgamma9/Vdelta2 T cell expansion, activation and cytotoxicity. METHODS: We investigated 1) cell expansion, 2) expression of TNFRII receptor, 3) perforin and gamma interferon (IFN) content, 4) release of granzyme A (GrA) and 5) phenotype changes, in vitro and in vivo, in Vgamma9/Vdelta2 T lymphocytes by means of fluores…

Cross-reactivity of anti-ssDNA antibodies with heparan sulfate in patients with type I diabetes mellitus

Anti-single-stranded–DNA antibodies cross-reactive with heparan sulfate were detected in serums of patients with type I (insulin-dependent) diabetes mellitus. The results suggested that heparan sulfate, the major glycosaminoglycan constituent of the glomerular basement membrane, may serve as a target antigen in vivo for cross-reactive anti-DNA antibodies. These polyreactive antibodies, directed toward repeating negatively charged units, may neutralize the heparan sulfate–associated polyanionic sites in the glomerulus, leading to an abnormal permeability of anionic plasma proteins.

Circulating immune complexes and platelet thromboxane synthesis in patients with insulin-dependent (type I) diabetes mellitus

Platelets from diabetic subjects with circulating immune complexes (CIC) synthesized greater amounts of thromboxane than did platelets from CIC-negative patients or controls. In view of the known action of CIC on platelet function, a relationship between these two factors may be suggested in the initiation and progression of microangiopathy in diabetes.

Serum levels of type III procollagen peptide in diabetes mellitus.

Serum levels of type III procollagen peptide (P-III-P) were investigated in 19 patients with type 1 (insulin-dependent) and in 48 (25 orally treated, 23 insulinized) patients with type 2 (non insulin-dependent) diabetes mellitus. Among patients with type 2 diabetes, 16 orally treated and 14 insulin-treated subjects had macrovascular complications. P-III-P levels were not correlated with the duration of diabetes and with glucose control, nor were there any significant sex and age differences in the levels. P-III-P values were significantly higher in the sera of insulin-treated non insulin-dependent diabetic patients with macroangiopathy. These high values (18.5 +/- 10.8 ng/ml) were in contra…

Phenotype and functional changes of Vγ9/Vδ2 T lymphocytes in Behçet's disease and the effect of infliximab on Vγ9/Vδ2 T cell expansion, activation and cytotoxicity

Introduction: Infliximab is a chimeric monoclonal antibody against tumor necrosis factor alpha (TNF-α) that has been introduced recently for Behcet's disease (BD) patients who were resistant to standard treatment. The aim of this study was to analyse the functional changes of Vγ9/Vδ2 T lymphocytes in both active and inactive disease and the effect of infliximab on Vγ9/Vδ2 T cell expansion, activation and cytotoxicity. Methods: We investigated 1) cell expansion, 2) expression of TNFRII receptor, 3) perforin and gamma interferon (IFN) content, 4) release of granzyme A (GrA) and 5) phenotype changes, in vitro and in vivo, in Vγ9/Vδ2 T lymphocytes by means of fluorescence-activated cell sorter …

Enhancement of endothelial cell E-selectin expression by sera from patients with active Behçet's disease: moderate correlation with anti-endothelial cell antibodies and serum myeloperoxidase levels.

We studied the in vitro E-selection expression of endothelial cells treated with sera from patients with Behcet's disease (BD) and factors (anti-endothelial cell antibodies, anti-neutrophil cytoplasmic antibodies, cytokines, and myeloperoxidase (MPO) that may contribute to adhesion molecule expression. A total of 21 patients with BD and 27 healthy controls were studied. In vitro E-selectin endothelial cell expression was investigated by ELISA after HUVEC incubation with sera or purified IgG from patients with BD and controls. Increased E-selectin expression was observed when endothelial cells were incubated with sera from patients with active disease or from patients with circulating anti-e…

Behçet's disease and coeliac disease

Inhibition of Fcγ Receptors in the Plasma of Subjects with Down's Syndrome

Abstract Subjects with Down's syndrome have several immunological abnormalities. We examined the sera of 29 subjects with Down's syndrome for the presence of Fcγ receptor blocking and for the presence of anti-ssDNA antibodies by EA rosette inhibition. Fifty-five percent of Down subjects had levels of inhibition above the upper limit of normality in comparison to 7% of normal controls. The finding that after polyethylene glycol precipitation of selected sera giving high levels of EA rosette inhibition there was a reduction or a disappearance of the EA rosette inhibition could indicate that the blocking factors detected behaved as immune complexes. Since almost all subjects with anti-ssDNA an…

The Terminal Complement Complex (TCC) in the Plasma of Patients with Type 1 Diabetes Mellitus. Relationship with Albumin Excretion Rate

Increased TCC levels were found to be present in the plasma of patients with type 1 diabetes associated with the presence of anti-heparan sulfate antibodies and increased urinary excretion of albumin. The authors suggest a role of terminal complement activation in the pathogenesis of diabetic nephropathy.

IgG anti-endothelial cell antibodies (AECA) in type I diabetes mellitus; induction of adhesion molecule expression in cultured endothelial cells

SUMMARYAECA were detected in 25 of 71 patients with type 1 diabetes mellitus and in two of 33 healthy subjects. Patients with diabetes of &amp;lt; 1 year duration and those with long-standing disease had the highest levels of these antibodies. Inhibition studies suggest that at least part of the AECA reactivity is due to cross-reactive anti-ssDNA antibodies. AECA-positive sera were able to increase intercellular adhesion molecule-1 (ICAM-1) and E-selectin on human umbilical vein endothelial cells (HUVEC). Increased binding of polymorphonuclear (PMN) cells was also found to accompany raised E-selectin expression. Soluble ICAM-1 and E-selectin were also found to be increased in the sera of AE…

Long-term anti-tumour necrosis factor therapy reverses the progression of carotid intima–media thickness in female patients with active rheumatoid arthritis

The objective of the study is to evaluate the effect of TNF inhibition on carotid thickness over a 2-year period. 144 women with RA diagnosed according to ACR criteria, without clinical evidence of cardiac and/or vascular disease were enrolled and compared with 78 matched controls. All patients received methotrexate (15–20 mg weekly) for 3 months. Responders (n = 79) continued to be treated with methotrexate, non-responders (n = 40) moved to methotrexate plus a TNF alpha antagonist. Echosonographic studies of carotids were obtained before and after 2-year follow-up. A significant decrease of ca-IMT was observed in anti-TNF-treated patients (P < 0.001); on the other hand, no significant vari…