Involvement of the IL23/Th17 Pathway in the Pathogenesis of Tunisian Pemphigus Foliaceus.

Pemphigus foliaceus (PF) is a rare autoimmune skin disease caused by anti-Dsg1 pathogenic autoantibodies. It is considered as a Th2-mediated disease. Likewise, Th17 cells were recently described in the pathogenesis of the disease but their role is still unclear. We aimed to unravel the eventual implication of the IL23/Th17 pathway in the development of PF. A case-control study was conducted on 115 PF patients and 201 healthy controls using PCR-RFLP and AS-PCR methods. SNPs in IL23R, RORγt, IL17A, IL17F, IL17AR, TNFa, and STAT3 genes were genotyped. mRNA expression of IL23R and RORγt was evaluated using Q-PCR. The frequency of circulating Th17 cells was analyzed by flow cytometry. Genetic associations between IL23R>rs11209026, IL17A>rs3748067, IL17F>rs763780, and TNFa>rs1800629 and the susceptibility to PF were reported. Moreover, we revealed a significant increased frequency of circulating CD4+IL17+ cells as well as higher mRNA levels of RORγt and IL23R in PBMCs of patients. However, no significant increase of RORγt and IL23R mRNA expression was observed in lesional skin biopsies. In spite of the little size of specimens, our results provide converging arguments for the contribution of the IL23/Th17 pathway in the pathogenesis of PF.

Effect of cannabis and tobacco on emphysema in patients with spontaneous pneumothorax.

PURPOSE: To compare imaging findings on thoracic computed tomography (CT) examination in patients with primary spontaneous pneumothorax (SP), depending on their tobacco and/or cannabis consumption. MATERIALS AND METHODS: A total of 83 patients who had thoracic CT for primary SP were prospectively included. There were 65 men and 18 women with a median age of 33 years (IQR: 27; 44 years). The patients were further categorized into three groups according to their smoking habits. Thirteen patients were non-smokers, 38 were tobacco only smokers and 32 were tobacco and cannabis smokers. CT examinations were retrospectively reviewed for the presence of blebs, centrilobular and paraseptal emphysema and lung nodules in each group for comparison. RESULTS: Emphysema was detected in 43/85 patients (51.8%), including 1/13 patients (7.7%) in the non-smoking group, 19/38 patients (50%) in the tobacco only group and 23/32 patients (71.9%) in the tobacco and cannabis smokers, with no difference between tobacco only and tobacco and cannabis smokers. No differences in type and location of emphysema was found between tobacco only and tobacco and cannabis smokers. Tobacco and cannabis smokers with emphysema were significantly younger than tobacco only smokers with emphysema (35 vs. 46 years, respectively) (P=0.009). CONCLUSION: The prevalence of emphysema visible on CT is not different between tobacco and tobacco/cannabis smokers, however, it occurs at a younger age in tobacco and cannabis smokers. This result suggests that cannabis, when added to tobacco, may lead to emphysema at a younger age.

[Bronchial carcinoid tumor and recurrent pneumothoraxes]. / Tumeur carcinoïde bronchique révélée par un pneumothorax récidivant.

Pneumothorax is a rare clinical manifestation of lung cancer. It can exceptionally reveal a bronchial carcinoid tumor. We present the case of a 27-year-old woman in whom recurrent pneumothoraxes were the clinical manifestation of a bronchial carcinoid tumor. The interest for chest computed tomography and bronchoscopy to identify etiology of secondary pneumothoraxes will be discussed.

Relevant genetic polymorphisms and kidney expression of Toll-like receptor (TLR)-5 and TLR-9 in lupus nephritis.

Toll-like receptor (TLR) genetic polymorphisms may modify their expression causing inflammatory disorders and influencing both susceptibility and severity of lupus erythematosus. We aim to determine whether TLR-5 and TLR-9 gene polymorphisms are implicated in the susceptibility to systemic lupus erythematosus (SLE) and lupus nephritis (LN) and to evaluate their expressions and distributions in renal LN patients' biopsies. The frequencies of two SNP in the TLR-9 gene and one in the TLR-5 gene was examined in 106 SLE patients (among them 37 LN patients) and in 200 matched controls by polymerase chain reaction-restriction fragment-length polymorphisms (PCR-RFLP) analysis. TLR-9 and TLR-5 expressions were assessed by reverse transcription (RT)-PCR and immunohistochemistry carried on LN renal biopsies compared to healthy renal tissue. A significant genotypic and allelic association was revealed between TLR-9-rs352140 and both SLE and LN (P < 0·05). The TLR-9 transcript level was significantly higher in LN biopsies compared to control (P < 0·05). This increase was observed histochemically in the tubulointerstitial compartment. TLR-9 was detectable in LN glomeruli patients but not in normal control glomeruli. No allelic nor genotype association was found with TLR-5-rs5744168 in SLE. but the T allele and the TT genotype were raised significantly in the LN group (P < 0·05). A significant increase in TLR-5 gene expression in LN biopsies, which contrasted with normal kidneys (P < 0·05), was confirmed by an intense and diffuse staining for TLR-5 only in LN tubules (P < 0·05). Our data show that TLR-5 and TLR-9 are susceptible genes to LN and that their expression is dysregulated in LN patients' kidneys, supporting a role of these mediators in the pathogenesis of LN.

[Flexible endoscope in thoracic surgery: CITES or cVATS?]. / L'endoscope souple en chirurgie thoracique, quel abord: CITES ou cVATS?

Early pain and persistent parietal disorders remains a major unresolved problem in thoracic surgery. Thoracotomy and the use of multiple ports in most Video Assisted Thoracic Surgery (VATS) procedures are the major cause of this persistent pain. For the last decade, a few publications describing the use of either single incision VATS and cervical thoracic approaches have been reported without significant results in comparison with current used techniques. Intercostals compression during surgery and early after by intercostals chest tube placement, are probably the major cause of postoperative pain. Flexible endoscope is currently used in several surgeries and will take more and more importance in our daily use in thoracic surgery. Instrument flexibility allows its use through minimally invasive approaches and offers a very interesting intra-thoracic navigation. We describe here the first use in France of a flexible endoscope in thoracic surgery through a single cervical incision to perform simultaneous exploration and biopsies of the mediastinum and right pleura using the original approach of Cervical Incision Thoracic Endoscopic Surgery (CITES).

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. OBJECTIVE: The purpose of this study is to examine the lipid peroxidation, protein oxidation and antioxidative profile in Tunisian pemphigus foliaceus (PF) patients. METHODS: Malondialdehyde (MDA), conjugated dienes (CD), protein thiol levels, catalase (CAT) and superoxide dismutase (SOD) activities were evaluated in skin biopsies of 13 patients compared to biopsies of 7 healthy controls. RESULTS: Oxidative stress was confirmed in these three types of patient biopsies as compared to controls. Thus, MDA, CD levels and catalase CAT and SOD activities were significantly increased in lesional, perilesional and normal biopsies of PF patients than in those of control subjects. Protein oxidative was confirmed by lower levels of protein thiols in lesional, perilesional and normal biopsies than in control's biopsies. Otherwise, in patients, a significant rise of these biomarkers was observed in lesional and perilesional biopsies compared with normal biopsies. CONCLUSION: This study shows that oxidative stress could be involved in the pathogenesis of PF by the spread of skin lesions and/or by the increase in auto-antibodies' reactivity.

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 Bonferroni's 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.

Association of the RAVER2 gene with increased susceptibility for ulcerative colitis.

Crohn's disease (CD), ulcerative colitis (UC), systemic lupus erythematosus (SLE) and autoimmune polyglandular syndromes (APS) are autoimmune diseases (ADs) that may share common susceptibility pathways. We examined ribonucleo-protein, polypyrimidine tract-binding protein (PTB)-binding 2 (RAVER2) loci for these diseases in a cohort of 39 CD cases, 67 UC cases, 93 SLE cases, 60 APS cases and 162 healthy control subjects of Tunisian origin. We genotyped 3 SNPs of RAVER2 (rs2780814, rs1333739 and rs2780889) and evaluated it genetic association with each ADs, using X2-test. For each association, odds ratio (OR) and 95% CI were calculated. We show that rs2780814 is significantly associated with UC (P = 0.00016, P(corr) = 0.00048, OR = 3.66 (1.82; 7.34)). We also observed a trend of possible association to SLE (P = 0.023, P(corr) = 0.69, OR = 2.19 (1.1; 4.36)). None of these RAVER2 SNPs were associated with CD and APS susceptibility. These findings establish RAVER2 as a new UC genetic susceptibility factor and reveal a genetic heterogeneity of the associated polymorphisms and risk alleles between ADs suggesting different immunopathological roles of RAVER2 in these diseases.

Spectrum and workload of consultation activities in a Belgian tertiary paediatric cardiac centre.

BACKGROUND: Few data are available on the spectrum and frequency of issues addressed in the paediatric cardiology consultation service of tertiary academic hospitals. METHODS: Those activities were collected prospectively during 6 months. RESULTS: A total of 967 consultations were performed. The origin was mostly the medical ward (n = 535), the intensive care unit (n = 195), the neonatal unit (n = 97), the operating room (n = 84) and the nursery (n = 44). In 553 cases, a heart disease was previously known and the most common reasons of consultation were postoperative (n = 279) and preoperative evaluations (n = 129). Thirteen newborns had a prenatal suspicion of congenital heart disease, which was confirmed in 11 cases. For the other 401 consultations, the most common clinical concerns included cardiac function in oncological disease (n = 60), murmur (n = 48), syncope (n = 33), diabetes mellitus (n = 28), prematurity (n = 27), syndrome (n = 19), unexplained stridor or respiratory distress (n = 19) and unexplained fever (n = 15). There were new diagnoses of congenital heart disease, acquired heart disease and arrhythmias in 35, 17 and 5 cases, respectively. CONCLUSIONS: The workload of the paediatric cardiology consultation service is increasing alarmingly. These data may be helpful in future planning of consultant manpower and in curriculum development in cardiac training of students and residents.

Protective effect of 17beta-estradiol on oxidative stress and liver dysfunction in aged male rats.

In aging liver oxidative stress increases due to the decrease in antioxidant bio-molecules such as estrogens which can be modified by hormonal replacement therapy (HRT). With this in mind, we hypothesized that age-related decline in steroidogenesis may be associated with the impairment of the antioxidant defense cells in liver, the increase in lipid peroxidation, hepatic dysfunction and histological changes; estrogens prevent all these changes induced by aging. 17beta-estradiol treatment was initiated in 12 month-old Wistar rats, and continued until 18 months of age. Our results showed that 17beta-estradiol (E2) level in the serum of the aged untreated rats was reduced by -32% in 18 month-old rats compared to the young animals (4-month-old). The superoxide dismutase (SOD), catalase (CAT), and gluthatione peroxidase (GPX) activities were reduced by -47, -46, and -29% respectively in old rat liver. In addition, the TBARs in liver and hepatic dysfunction parameters in plasma such as gamma-glutamyl transferase (GGT), phosphatase alkalin (PAL) as well as bilirubin level increased significantly in old rats, and histological changes were investigated. In E2-treated rats, protective effects were observed. Indeed, 17beta-estradiol attenuates all changes induced by aging. The 17beta-estradiol level was higher in old E2-treated rats compared to the control rats. Moreover, the SOD, CAT and GPX activities were higher by +28, +15, and +11% respectively. This anti-aging effect of estrogens was clarified by a lower level of lipid peroxidation and liver dysfunction parameters as well as by histological observation.

[Monoclonal gammapathies in Tunisia: epidemiological, immunochemical and etiological analysis of 288 cases]. / Gammapathies monoclonales en Tunisie: analyse épidémiologique, immunochimique et étiologique d'une série de 288 cas.

From July 1992 to December 2000, 288 cases of monoclonal gammapathy (MG) were collected at the university hospital of Sfax. The middle age of the patients at the time of the diagnosis was 62 years and 7 months with extremes to 18 months and 99 years and median to 64 years. One hundred and eighty-two patients were men and 106 women. Among the 270 observations for which aetiology has been established, 73 were classified MG of undetermined significance (MGUS), 160 myeloma (or plasmocytoma) and 37 other malignant MG (Waldenstrom's macroglobulinemia: 13, lymphoma: 9, alpha heavy chains disease: 6, primary amyloidosis: 5, chronic lymphocytic leukaemia: 4). Rheumatological affections (19.2%), infections and renal failure (10% each), haematological and autoimmune diseases (9.6% each) were pathologies most often associated with MGUS. Agarose gel electrophoresis did not show a monoclonal peak in 16% of the cases. In the 242 patients with a peak on electrophoresis, the peak was in the beta zone in 22% of cases and in the gamma zone in 78% of cases. The IgG isotype represents more than the half of the cases of our set (51.7%). IgG is even more predominant in the MGUS group (65.8%). The IgA isotype counts for 20.8% of the cases in our set and the free light chains (kappa or lambda) for 13.6% of the cases whereas the IgM represents 8.7% only of the 288 cases of our set which involves three cases of IgD myeloma and six cases of biclonal gammapathy.

[Determination of anti-transglutaminase antibodies in the diagnosis of coeliac disease in children: results of a five year prospective study]. / Dosage des anticorps anti-transglutaminase dans le diagnostic de la maladie coeliaque de l'enfant: résultats d'une étude prospective sur cinq ans.

AIM: To evaluate the interest of IgA antibodies to tissue transglutaminase in the diagnosis of children coeliac disease compared with anti-endomysium and anti-gliadin antibodies. SUBJECTS AND METHODS: Seventy children with coeliac disease (mean age: 5 years and 8 months) and 99 disease controls (mean age: 4 years and 5 months). IgA anti-transglutaminase were tested by ELISA using a human recombinant tissue transglutaminase. IgA anti-endomysium were detected by indirect immunofluorescence on monkey oesophagus. RESULTS: The middle rate of IgA anti-transglutaminase was 101.06 units in patients and only 0.47 unit in controls. IgA anti-transglutaminase and IgA anti-endomysium were in agreement in 98.8% of cases; only two cases were discordant (+/- and -/+). Globally, the two markers had the same sensitivity (90%), specificity (98%), negative (93.2%) and positive (96.9%) predictive values. For anti-gliadin antibodies, the IgG were more sensitive (88.6%) and the IgA more specific (93.9%). CONCLUSION: IgA anti-tissue transglutaminase can be used instead of IgA anti-endomysium as a serological marker of screening and diagnosis of coeliac disease in children after 3 years.

[Carcinomatous meningitis revealing a cancer: study of two cases]. / Meningite carcinomateuse révélatrice de cancer: étude de deux cas.

Meningeal Carcinomatosis (MC) is rare (4 to 5% of patients with solid tumors). We report two cases. The first case is a 53 year-old man presenting flaccid paraplegia and the second is a 76 year-old man presenting a clinical picture suggestive of normal pressure hydrocephalus. In the two cases, the diagnosis of MC was achieved by the demonstration of malignant cells in the CSF. Prognosis was poor in the two cases. The clinical presentation of MC is non specific and the diagnosis is only confirmed by demonstrating carcinomatous cells in CSF.

[Quality control in tumor marker values: methology, results and potential problems]. / Le controle de qualite dans le dosage des marqueurs tumoraux: methodologie, resultats et problemes poses.

Ensuring the quality is one of the first preoccupations of every biologist. However, measuring the circulating tumor markers could be more vital especially that the result is decisive for the diagnostic and the therapeutic attitude. In this study, we report methods used for an internal and external < or = quality control < or = program applied in the immunology laboratory of Sfax university hospital for the dosage of tumor markers AFP, CEA and CA15-3. The results obtained are analysed comparatively with those reported in literature. Factors causing discrepancies in the results of tumor marker measurements are recalled.

[Sensitivity, specificity and prognostic value of CEA in colorectal cancer: results of a Tunisian series and literature review]. / Sensibilite, specificite et valeur pronostique de l'ace dans le cancer du colon rectum: resultats d'une série Tunisienne et revue de la littérature.

In order to determine the sensitivity of CEA in the diagnosis of colo-rectal carcinoma, we studied a series of 48 patients with colo-rectal carcinoma (1992-1996). The sensitivity was at 52% with a reference value of 5 ng/ml and 68.7% for a reference value of 2.5 ng/ml. With a reference value of 5 ng/ml, the sensitivity of CEA was at 37% only for patients with colo-rectal carcinoma at Dukes B stage, 66.6% for patients at stage C and 75% for patients at stage D. The dosage of CEA was carried out with a sandwich immunoenzymatic technique in tube. There is no statistic significant correlation between the pre-operative rate of CEA and the localisation of the tumor and its histologic type; in contrast, it was significantly correlated with the ganglionnary metastasis. A significant relationship between the pre-operative rate of CEA and the Dukes stage was found for a reference value of 10 ng/ml but not for a reference value of 5 ng/ml. We calculated the specificity of the CEA for the cancers of colon and rectum which was at 76.98% with a reference value of 5 ng/ml and 86% with a reference value of 10 ng/ml.