Imed Ben Ghorbel

Expression of Th-17 and RORgammat mRNA in Behçet’s Disease

Summary Background To investigate plasma IL-17 level and the expression of Th17 cell transcription factor RORγt in the pathogenesis of Behçet’s Disease (BD). Material/Methods Blood samples were collected from 73 patients with BD (45 patients were in active stage), 20 systemic lupus erythematosus (SLE) and 12 multiple sclerosis patients (MS). Twelve patients with BD were investigated both in their active and remission stages. Samples were processed to detect IL-17A level in plasma by enzyme-linked immunosorbent assay (ELISA). Related gene expression was assessed by real-time reverse transcription polymerase chain reaction. Function of Th17 cells in active BD patients with erythema nodosum (EN)-like eruption was studied in relation to human umbilical vein endothelial cells (HUVECs). Results We demonstrated the presence of Th17 cells and RORγt among the peripheral blood mononuclear cells (PBMC). The percentage of circulating Th17 cells and the ability to produce interleukin-17A (IL-17A) were increased in samples derived from patients with active BD, MS and SLE patients. We observed that IL-17A from patients with active BD could induce adhesion molecule messenger RNA expression in HUVECs. Conclusions RORγt determined Th17 cell might be involved with increased IL-17A in BD. Our results indicate that IL-17 contributes to the active proinflammatory pattern that is characteristic of inflammatory diseases and patients with active BD.

RORC and Foxp3 axis in cerebrospinal fluid of patients with Neuro-Behçet's Disease

Neurological manifestations are present in 5% to 30% of patients with Behçets disease (BD). Neuro-Behçets Disease (NBD) is hypothetically caused by T helper (Th) cells, which development is dependent on the expression of lineage-specific transcription factors. Cerebrospinal fluid (CSF) mRNA expression of TBX21, GATA3, RORC, FOXP3 and EBI3 were assessed in 18 NBD patients and 26 controls disease [16 noninflammatory neurological disease (NIND) and 10 headache attributed to Behçets disease (HaBD)]. Expression of TBX21 (Th1), RORC (Th17) and Foxp3 (Treg) were increased in NBD patients compared to HaBD and NIND patients. EBI3 and Th2-associated GATA3 expressions were found to be decreased (P<0.0001 and P<0.0001) in NBD patients. Analysis of transcription factor ratios, revealed an increase in the RORC/FOXP3 and TBX21/GATA3 ratios in NBD patients (P<0.0001; P<0.0003). Our findings indicate that both Th1 and Th17 mRNA expressions involving a possible impairment of Treg cells. This might play a role in CSF-NBD inflammation, permitting activation of harmful T cell subpopulations. The TBX21/GATA3 and RORC/FOXP3 ratios dysregulations in NBD are consistent with those reported in other inflammatory diseases and indicating the plasticity existing between Th1, Th17 and Treg cells during inflammation.

Associations of vitamin D receptor gene polymorphisms FokI and BsmI with susceptibility to rheumatoid arthritis and Behçet's disease in Tunisians

OBJECTIVES Reports of immunomodulating effects of vitamin D suggest a need for examining allele and genotype frequencies of the vitamin D nuclear receptor gene (VDR) in patients with autoimmune diseases. T-helper-1 (Th1) counts in peripheral blood are increased in both rheumatoid arthritis (RA) and Behçets disease (BD). We studied VDR polymorphisms in patients with these two diseases in Tunisia. METHODS In 108 patients with RA, 131 patients with BD, and 152 controls, we studied FokI and BsmI VDR polymorphisms, using the restriction fragment length polymorphism technique. RESULTS The FokI polymorphism alleles and genotype were significantly more common in the RA group than in the controls (P=0.001 and P=0.005, respectively). The FokI F allele and F/F genotype were significantly associated with BD (P=0.0003 and P=0.002, respectively). Furthermore, in the group with BD, the FokI polymorphism was significantly associated with the presence of vascular manifestations (P=0.006). In patients with RA, the FokI polymorphism was significantly associated with female gender (P=0.003). No significant associations were found between the Bsm1 polymorphism and RA or BD. CONCLUSION The VDR F allele is associated with RA and BD in Tunisians.

Association of right heart thrombosis, endomyocardial fibrosis, and pulmonary artery aneurysm in Behçet’s disease

A 29-year-old man with a 5-year history of Behçets disease was admitted for fever, dyspnae, chest pain, and hemoptysis. A diagnosis of right ventricle and atrial thrombosis associated with a pulmonary artery aneurysm was made. The patient was treated with anticoagulants and prednisone. Since hemoptysis persisted, surgical excision of the intracardiac thrombosis was performed and histological findings were consistent with organizing thrombus and endomyocardial fibrosis. Transesophageal echocardiography 6 months later showed recurrence of the right ventricle thrombosis. A course of 6-monthly boluses of intravenous cyclophosphamide was begun. Currently, at 2 years of follow-up, the patient is asymptomatic.

Characteristics of neurological manifestations of Behcet's disease: A retrospective monocentric study in Tunisia

OBJECTIVE The aim of the present study was to analyze demographic, clinical and genetic features of Behçets disease patients with neurological involvement through a monocentric study of a homogenous group of hospitalized patients observed in the same department and to compare them with those of other ethnic and geographic groups. METHODS Four hundred and thirty Behçets disease (BD) patients were retrospectively studied. Diagnosis of BD was made according to the international study group for Behçets disease criteria. Patients with neurological findings suggestive of involvement of the nervous system by BD were further studied according to clinical examination, laboratory tests and neuroradiological investigations. RESULTS Neurological involvement was observed in 121 patients (28.1%). The mean age at neuro-Behçets disease (NBD) onset was 29.7 years. Average disease duration of BD before neurological manifestations onset was 6.4 years. Male to female ratio was 1.8. Of the 121 NBD patients, parenchymal involvement occurred in 74 patients (61%). Among them 26 (21.4%) presented with brainstem involvement, 24 (19.8%) with hemispheric involvement and 2 (1.6%) with spinal cord involvement. Non-parenchymal NBD occurred in 47 patients (39%). Involvement of the main vascular structures (Vasculo-NBD) was the most common non-parenchymal NBD lesion found in 35 patients (28.9%) consisting of cerebral vein thrombosis (CVT) in 24 cases and cerebral arterial thrombosis in 11 cases. Forty-nine (40.5%) patients with NBD have been followed-up for a median of 3 years (range 1-19 years). Forty-one of them recovered well without significant residual disability, 5 patients made no improvement and are left with severe neurological impairments and 3 died. Male gender and CNS parenchymal lesions occurrence were significantly associated with a poorer prognosis. CONCLUSION Clinical and epidemiological features of NBD are various. In our Tunisian cohort of NBD patients the main characteristic features were male predominance, a relatively high prevalence of CVT, a low prevalence of intra-cranial hypertension and a significant lower frequency of HLA-B51 haplotype.

TULUP (TUnisian LUPus): a multicentric study of systemic lupus erythematosus in Tunisia.

Clinical features of systemic lupus erythematosus (SLE) have been described from different geographical regions around the world. However, data from North African countries, including Tunisia, are scarce.

Contribution of Hla-B51 in the susceptibility and specific clinical features of Behcet's disease in Tunisian patients

BACKGROUND Many researchers have tried to investigate the association of HLA-B51 with the severity and the clinical features of BD with conflicting results. METHODS We aimed at investigating the association of HLA-B51 with demographical and clinical manifestations as well as the severity of BD, by studying 178 native Tunisian BD patients, fulfilling the International Study group criteria for the BD classification recruited from the Department of Internal Medicine, Rabta Hospital in Tunis and compared with 125 native Tunisian healthy age and sex matching volunteers. RESULTS According to our findings, the frequency of HLAB 51 was significantly higher in BD patients than in controls (p<0.001). Positive pathergy test (PPT) (p = 0.01) and retinal vasculitis (p = 0.045), were significantly more frequent in HLA B51(+) patients, while the frequency of arterial aneurysms (p = 0.009) and neurological involvement, especially the parenchymal involvement (p<0.001), were significantly and clearly higher in HLA B51(-) patients. The patients without HLA B51 had a significantly less severe disease (p = 0.001). Discussion/conclusion We conclude that HLA B51 is a predisposing marker for BD in our population as in most ethnic groups. It seems to be associated with a subgroup of BD patients characterized by a higher frequency of ocular involvement and PPT, but a lower frequency of arterial aneurysm and neurological involvement, and a less severe disease course.

Vascularite à anticorps anticytoplasme de polynucléaires neutrophiles induite par le benzylthio-uracile

Resume Introduction De nombreuses observations de vascularites a anticorps anticytoplasme de polynucleaires neutrophiles (ANCA) secondaires aux antithyroidiens de synthese ont ete decrites mais seuls 2 cas ont ete imputes au benzylthio-uracile. Observation Chez une, femme de 36, ans 3 ans apres un traitement par benzylthio-uracile, une insuffisance renale rapidement progressive est apparue, en rapport avec une nephropathie glomerulaire extra-capillaire pauci-immune associee a des lesions de vascularite necrosante. La recherche des p-ANCA etait positive avec une specificite anti-myeloperoxydase. Elle a ete traitee par des corticoides et 6 bolus mensuels de cyclophosphamide puis de l’azathioprine, avec une bonne amelioration de l’insuffisance renale et une diminution significative de la proteinurie. Cependant le taux de p-ANCA n’a pas varie. Conclusion Les vascularites a ANCA sont une complication rare mais grave des traitements par antithyroidiens de synthese de type thio-uraciles. Un dosage des ANCA doit etre effectue en cas d’apparition d’une manifestation systemique en cours de traitement.

Pleural myelomatous involvement in multiple myeloma: five cases.

Pleural myelomatous involvement in multiple myeloma (MM) is rare, occurring in less than 1% of cases. We retrospectively studied five cases of patients with MM who developed myelomatous pleural effusions. Three men and 2 women with a mean age of 61 years presented with myelomatous pleural effusion. The pleural fluid electrophoresis revealed a peak of IgG in three cases, of IgA in one case, and of lambda light chains in one case, which were identical to that in the sera of the patients. Detection of typical plasma cells in pleural fluid cytology was contributive, and histologic confirmation by pleural biopsy was positive in four cases. Treatment consisted of chemotherapy. The clinical outcome was initially good, but relapses occurred in all cases early and were complicated by fatal infections. Myelomatous pleural effusion is a rare affection. It is usually a late complication associated with poor prognosis.

Pseudotumoral brain lesion as the presenting feature of primary Sjögren's syndrome

BACKGROUND The frequency and type of central nervous system involvement in primary Sjögrens syndrome (pSS) remain controversial. Brain magnetic resonance imaging (MRI) abnormalities in pSS are usually discrete hyperintense areas in the white matter. Tumefactive brain lesions have been rarely reported. CASE REPORT We describe a 31-year-old woman who exhibited transcortical motor aphasia, hemiparesis and partial motor seizures as the initial manifestation of pSS. Brain MRI revealed a large frontoparietal lesion extending into the corpus callosum. The patient had spontaneous recovery and developed sicca symptoms 6 months after onset. Primary SS was diagnosed on the basis of clinical features, abnormal Schirmer test findings, high levels of anti-La/SSB antibodies and positive salivary gland biopsy results. CONCLUSION The present case suggests that a pseudotumoral brain lesion can occur as an initial symptom of pSS.