M. Ben Ayed

Anti‐desmoglein 1 antibodies in healthy related and unrelated subjects and patients with pemphigus foliaceus in endemic and non‐endemic areas from Tunisia

Background  Pemphigus foliaceus is an autoimmune blistering skin disease characterized by the production of pathogenic IgG autoantibodies directed against desmoglein 1.

Contribution of PTPN22, CD28, CTLA-4 and ZAP-70 variants to the risk of type 1 diabetes in Tunisians.

Type 1 diabetes (T1D) is caused by an immune-mediated destruction of the insulin-producing β-cells. Several studies support the involvement of T cell activation molecules. In order to underline the role of the genes involved in this pathway, we investigated, using the Sequenom MassARRAY platform, polymorphisms of sixteen single-nucleotide polymorphisms (SNPs) belonging to PTPN22, CD28, CTLA-4, and ZAP-70 genes in 76 T1D patients and 162 unrelated healthy controls from Southern Tunisia. We confirmed the association with PTPN22 (rs2476601, Corrected P (Pcorr)=0.002, OR=6.20) and CD28 gene (rs1879877, Pcorr=0.003; OR=4.27 and rs3181096, Pcorr=0.02; OR=1.73). We also identified an association with rs17695937 of ZAP-70 gene (Pcorr=0.02, OR=1.87). Our results suggest a significant effect on T1D susceptibility for A-C-A-G-C and T-C-C-T-A-C haplotypes, of ZAP-70 and CD28 genes, respectively. In addition, (A-G-C) combination of ZAP-70/CD28 gene was significantly increased in T1D patients as compared to controls, suggesting the possible interaction between these genes. These results confirm the involvement of PTPN22 and CD28 genes in the genetic susceptibility to T1D. Interestingly, ZAP-70 seems to contribute to the susceptibility to the disease in our population. However, this finding has to be confirmed in further studies.

Polymorphisms of HLA microsatellite marker in Tunisian pemphigus foliaceus.

Pemphigus foliaceus (PF) is an autoimmune blistering skin disease that partly results from genetic factors, especially from human leucocyte antigen (HLA) class II genes. Several data have reported the involvement of microsatellite (STR) markers across different regions of the HLA in many auto-immune diseases. To test the hypothesis of the existence of a major HLA haplotype predisposing to PF, we analyzed six polymorphisms of microsatellite loci at 6p21.3-21.4 spanning HLA: D6S291, D6S273, TNFa, MICA, D6S265 and D6S276 in 81 PF patients compared to 123 healthy individuals recruited from the south of Tunisia. In this study, after Bonferronis correction, 3 STR alleles from the TNFa locus were associated with the disease: the allele TNFa(∗)2 (p(c) = 4.2×10(-6)) and, at a lower level, the TNFa(∗)5 (p(c) = 0.014) as susceptibility alleles and TNFa(∗)6 (p(c) = 0.014) as protective ones. Furthermore, the expression of the TNFa(∗)2/TNFa(∗)5 genotype seem to confer susceptibility to PF (p = 0.00001, OR = 11.25). Interestingly, no significant LD was found between TNFa2/TNFa5 alleles and DRB1(∗)03/DRB1(∗)04 alleles. However, the multivariant regression analysis indicates that both the HLA class II and the TNFa alleles remained significant (p < 0.001). Although, these findings rejected our hypothesis on the existence of HLA susceptibility haplotype, they assessed the role of TNFa loci. Accordingly, TNFa seem to contribute to the aethiopathogenesis of Tunisian endemic PF may be by the induction of a high TNFα production which is known to enhance the autoimmune cascade of the disease.

Biomarkers of oxidative stress in epidermis of Tunisian pemphigus foliaceus patients

Background  Reactive oxygen species play a key role in the development of many dermatological disorders.

Spectrum of autoantibodies other than anti-desmoglein in pemphigus patients

Background  Pemphigus is a life‐threatening autoimmune blistering disease mediated by autoantibodies against adhesion molecule of the skin. Its concurrence with systemic and organ‐specific autoimmune disease was described in case reports.

HLA-DRB1/DQB1 susceptibility for autoimmune polyglandular syndrome type II and III in south of Tunisia

OBJECTIVES The aim of our study was to investigate the association of HLA-DRB1 and HLA-DQB1 alleles with autoimmune polyglandular syndromes (APS) type II and III in a southern Tunisian population. PATIENTS AND METHODS Sixty-two unrelated patients with APSII (n=20) and APSIII (n=42) and 146 healthy controls were genotyped for HLA class II alleles (DRB1*, DQB1*) by PCR-SSP technique. RESULTS An increased frequencies of HLA-DQB1*03:02 (P=0,02; OR=2.98) in APSII patients, HLA-DRB1*03 (P=310(-6); OR=4.28) and HLA-DQB1*02:01 (P=0.04; OR=1.95) in APSIII patients were found compared to healthy controls. Study of the HLA-DRB1*;DQB1* haplotype frequencies showed a higher occurrence of DRB1*04;DQB1*03:02 and DRB1*03;DQB1*02:01 in APSII patients (P=410(-3); OR=3.31 and P=0.03; OR=2.74 respectively) whereas APSIII was only associated with DRB1*03;DQB1*02:01 (P=7.210(-8), OR=4.71). CONCLUSION Our data suggest that the variation in class II HLA alleles and haplotypes could be a genetic factor involved in the susceptibility of APS syndrome.INTRODUCTION The mosaicism 45, X/46, XY is a gonosomal abnormality characterized by a broad phenotypic spectrum, ranging from women with or without Turner syndrome stigmata, to men apparently normal, passing by the ambiguous phenotypes with variable virilisation of external genitalia. From the histological point of view, several situations may arise. PATIENTS AND METHODS We analyzed the clinical, hormonal, sonographic, and genitographics data, as well as peroperative and histological findings for five cases of mosaicism 45, X/46, XY, and we discussed treatment performed. RESULTS The mean age of patients was 6.6 years, two had a female phenotype with clitoral hypertrophy (one of them had Turner syndrome stigmata), one had a normal male phenotype with bilateral cryptorchidism and two had an ambiguity of external genitalia assigned to male. Short stature was noted for four patients. Surgical exploration concluded to the diagnosis of mixed gonadal dysgenesis for four of our patients. No cases of gonadoblastoma have been reported, for girls a prophylactic gonadectomy was performed, for boys the streak gonad was resected and the dysgenetic testis biopsied and preserved, subject for constant monitoring. CONCLUSION This heterogeneity indicate the importance of an accurate clinical and histological evaluation of any patient presenting with 45, X/46,XY mosaicism.

Un insulinome géant : à propos d’un cas

Islet-cell tumors are the most common neuroendocrine tumors that arise from the endocrine pancreas. They are typically benign and sporadic. Diagnosis is generally established late because clinical signs lack specificity. The insulinoma is difficult to localize since it is very small in size, often not exceeding 2cm. We report an exceptional case of giant insulinoma initially revealed by a pseudo-polycythemia in an 80-year-old man. He had been treated for hypertension for a few months. Routine biological investigations showed elevated hematocrit and haemoglobin, suggesting Vaquez disease. History taking revealed recent episodes of nocturnal agitation. On admission, he had reddish skin with a suspected enlarged spleen, but total blood volume was normal. Imaging studies showed a voluminous tumor located between the pancreas and the spleen. The presence of an insulinoma was confirmed on the basis of an elevated level of proinsulin at the time of an asymptomatic episode of hypoglycemia. Spleno-pancreatectomy was performed. Histopathological examination revealed a malignant, well-differentiated neuroendocrine malignant tumor.

Cytokine gene polymorphisms in Tunisian endemic pemphigus foliaceus: a possible role of il-4 variants.

Polymorphism in the genes of TH2 cytokines and/or theirs receptors can influence serum cytokine levels in and the switch to the pathologic IgG4 auto-antibodies. In order to underline the role of these genes in the aethiopathogenesis of Pemphigus Foliaceus, we conduct a familial and a case control studies including 80 Tunisian patients, 147 related subjects and 160 matched healthy controls. We investigated, by PCR-RFLP technique, seven nucleotide polymorphisms: rs2243250 in promoter region of IL4 gene, rs47877948, rs3024530 and rs30246223 in the IL4R gene, rs1881457and rs205412 SNPs in IL13 gene and rs535036 in IL13RA2 gene. After Bonferroni adjustment, T allele and the TT genotype of IL4-590 were significantly increased in the PF patients group compared to healthy controls. This association was confirmed by the family study. Interestingly, the serum IL-4 levels were significantly increased in patients with the TT genotype compared to CT or CC genotypes. Interestingly, the IL4/IL13:T-A-C haplotype exhibited a significant effect on PF susceptibility. In addition, a significant gene-gene interaction between the IL4/IL4R (TACA) significantly increases in PF patients as compared to controls. These findings assess the role of the IL4/IL4R axis in the aethiopathogenesis of Tunisian endemic PF by the induction of a high transcriptional activity which could enhance the T-cell balance and inducing immunoglobulin isotype switching.

Localized genital porokeratosis in a female patient with multiple myeloma

© 2008 The Authors JEADV 2009, 23, 570–620 Journal compilation

Iatrogenic pyoderma gangrenosum following iodine-containing contrast media

© 2008 The Authors JEADV 2009, 23, 702–738 Journal compilation