Discussion sur les differentes theories avancees dans l'etiopathogenie du syndrome de Behcet: le systeme HLA, la theorie herpetique, la theorie streptococcique, la dualite polynucleaire-lymphocyte

Vascular endothelial growth factor (VEGF) stimulates angiogenesis, but is also pro-inflammatory and plays an important role in the development of neurological disease, where it can have both attenuating and exacerbating effects. Several studies have indicated that VEGF-A (VEGF) may play a role in the pathogenesis of neurological inflammatory diseases. To assess the role of VEGF in patients with Behçet's disease with neurological involvement, VEGF was measured in the cerebrospinal fluid (CSF) of 32 patients compared to a group of 12 patients with noninflammatory neurological diseases (NIND) and 14 patients with multiple sclerosis (MS). We have also studied the expression of mRNA-VEGF (VEGF-A) in CSF and in peripheral blood mononuclear cells. The mean VEGFCSF was significantly increased in neuro-BD and MS patients compared to NIND patients. There was an association between neuro-BD-VEGFCSF, and leukocyte count. A significant correlation was also observed between neuro-BD-VEGFCSF and CSF%CD4 cells. As a measure of the integrity of the blood-brain barrier Qalbumin was found correlated to VEGFCSF. VEGF mRNA was significantly increased in neuro-BD patients compared to NIND patients. These results indicate that, VEGF may be associated with the increased percentages of CD4 cell subpopulation. The role of VEGF is within the inflammatory cascade in the mediation of blood-brain barrier disruption and not specific to Behçet's.

Objective : To analyse proinflammatory Th1 and Th2 cytokines in patients with Behçet's disease (BD) in relation to disease activity. Methods : Forty-five BD patients (25 in active stage) were investigated with ELISA for estimation of cytokines levels. Furthermore, cytokines intracellular synthesis (IL-4 and IFN- n ) of CD4 + T cells was studied. Results : Active and in remission BD patients showed increased serum levels of Th1 (IFN- n, IL-12) and Th2 (IL-4, IL-6 and IL-10) cytokines. Active BD was characterized by a higher increase of IL-6, IL-10 and a striking increase of IL-17, IL-18 and IFN- n, compared to remission BD. Upon in vitro stimulation, the percentages of CD4 + T cells containing IFN- n and CD40L were higher in active BD compared to healthy controls. Conclusion : Our results suggest that the microenvironment of CD4 + T cells in active BD may induce the production of more cells committed to Th1 than in BD patients in remission and healthy controls.

Behçet's disease is a systemic condition of unknown cause characterized in 20 to 40% of cases by venous and/or arterial thrombosis that is not fully explained by the hemostasis disorders reported in the literature. The present study investigated resistance to activated protein C in 65 Behçet's disease patients, 75 normal subjects, and 70 patients with a history of isolated thrombosis. The test used involved predilution in factor V-deficient plasma. Activated protein C resistance was found in six Behçet's disease patients (9.2%), eight normal subjects (10.6%), and 21 patients with isolated thrombosis (30%). Of the 26 Behçet's disease patients (40%) with a history of thrombosis, only one had activated protein C resistance. Activated protein C resistance does not explain the increased risk of thrombosis in Behçet's disease patients.

Les lymphocytes T activees de patients souffrant de maladie de Behcet (MB) peuvent s'accumuler dans le tissu conjontif de l'epiderme participant ainsi au processus lesionnel. Nous avons etabli des clones de lymphocytes T a partir de biopsies cutanees. La frequence de clonage a partir de la peau est de f = 0.20 versus f = 0.20 a partir du sang autologue. Les clones obtenus a partir de la peau portent le phenotype CD4 + . L'analyse des clones CD4 + obtenus a partir de la peau et stimules par la concanavaline A, montrent une secretion importante diinterferon-γ, de facteur GAG. Ces memes clones secretent aussi du TNF-α. Nos resultats montrent que les lymphocytes T CD4 + obtenus a partir de la peau secretent des cytokines, capable de moduler les fonctions inoenunes de la peau chez les patients atteints de maladie de Behcet.

Thrombosis occurs in 20 to 30 % of patients with Behcet's disease (BD). Most of the reported hemostatic abnormalities are related to the inflammatory syndrom. We have assessed the activity of antithrombin III, protein C and protein S (PS), in 30 patients with BD and in 30 healthy controls. Thrombosis antecedents were found in 16 patients. Antithrombin III and protein C were within the normal range, however free PS and PSactivity were significantly decreased in patients as compared to control group. PS deficiency detected in eight patients, was associated to thrombosis in 6 of them. No correlation was found between free PS/total PS ratio and C4bBP levels. Antibodies to PS were screened by ELISA and were present in 6 patients, associated to PS deficiency in 4, and to thrombosis antecedents in 5 cases..PS deficiency was transient in two patients, associated to a persistant antiPS in one of them. These findings suggest that auto-immune acquired PS deficiency may be involved in the pathogenesis of thrombotic events in BD. © 1997 Elsevier Science Ltd

Digestive manifestations are uncommon in Behçet's disease. The authors reported 3 male patients between 20 and 30 years with Behçet's disease who developed surgical abdomen. Emergency surgical intervention found perfored ileal ulceration. Histological study of resection piece showed mainly intestinal angitis with periphlebitis, venous thrombosis and obliterant endarteritis.

OBJECTIVE Our aim was to investigate the TCR gamma delta+ subset in Behçet's disease (BD) inflammatory sites, which better reflects changes associated with the pathologic process than peripheral blood. METHODS Forty-five patients with active BD, 10 patients with recurrent aphthous ulcers, 12 patients with rheumatoid arthritis, 5 patients with noninflammatory neurologic diseases and 15 healthy individuals were studied. Three monoclonal antibodies TCR delta 1, BB3, and A13 were used to assess the percentage of TCR gamma delta+ in peripheral blood mononuclear cells (PBMC), in bronchoalveolar lavage and cerebrospinal fluid (CSF). CD11a/CD18 was used to study adhesion molecules. TCR gamma delta+ cells isolated by immunomagnetic separation were tested for cytolytic activity against K562 target cells after interleukin 2 stimulation. RESULTS The PBMC TCR gamma delta BB3+ subset was significantly increased in BD. In BD inflammatory sites, TCR gamma delta+ cells were also present, composed mainly of A13+ cells from these sites also expressed CD11a marker. TCR gamma delta+ cells from inflammatory sites displayed a higher cytotoxic activity than controls, mediated by the A13+ subset. CONCLUSION The accumulation of cytotoxic TCR gamma delta+ cells at the sites of inflammation suggests their involvement in the local injury process.

In this study, we have analyzed the clinical and serological features related to 16 Tunisian children in whom diagnosis of systemic lupus erythematosus was made before or at the age of 15. Renal involvement was found in 75% of cases and renal biopsies have mostly revealed severe histologic patterns. All of the patients who have been followed received corticosteroids and in some cases required additional cytotoxic drugs in order to control disease activity. Five children died in a context of a renal failure. This study of childhood lupus in Tunisia confirms that the clinical course of this disease in children is often aggressive.

Differentiation of Behcet's disease from the cryptogenic enteropathies can raise diagnostic and nosological problems. The segments of the digestive tract most commonly involved in Behcet's disease are the ileum and colon; rectal manifestations are exceedingly rare. We report six Behcet's disease patients who had rectitis with clinical and histological features reminiscent of ulcerative colitis. However the colon was normal. Immunopathological differences between the two diseases have been reported by other investigators.