OBJECTIVEBiclonal gammopathies (BGs) are rare situations characterized by the production of 2 monoclonal proteins. There are no available data on BGs in North Africa. We aimed to estimate the prevalence of BGs in our population and describe their clinical and laboratory features.METHODSWe conducted a 31-year retrospective study including patients with persistent double monoclonal bands based on the results of immunofixation/immunoelectrophoresis.RESULTSA total of 35 patients with available clinical data (sex ratio, M/F = 1.53; mean age, 70 ± 10.87 years [range, 45-90 years]) were included. The main associated conditions were multiple myeloma (MM) (40%), BG of undetermined significance (BGUS) (34%), and lymphoproliferative diseases (23%). Only one-third of the patients had 2 monoclonal spikes on serum protein electrophoresis. The most common paraprotein combinations were immunoglobulin (Ig)G-IgG (25%) and IgG-IgA (23%) with different light chains in one-half of the cases. The mean follow-up was 25.6 months (median, 12 months). No BGUS evolved into a malignant disease.CONCLUSIONBGs are rare in clinical laboratory routine but must be accurately identified by the pathologist. Our cohort is characterized by a high prevalence of BGUS compared with MM.

Le lupus érythémateux systémique (LES) est une maladie systémique auto-immune d'étiologie inconnue qui touche essentiellement les femmes à l'âge adulte. Le lupus pédiatrique est une entité rare. Nous rapportons une nouvelle observation. Il s'agissait d'un nourrisson âgé de 7 mois qui présentait des lésions cutanées purpuriques, une polyarthrite fébrile. Le bilan immunologique était positif (AAN et anti-ADN). Une amélioration clinique et biologique a été notée sous corticothérapie générale avec une récidive lors de la dégression du traitement.

Inflammatory bowel diseases (IBDs), consisting of ulcerative colitis (UC) and Crohn's disease (CD), are complex disorders with multiple genes contributing to disease pathogenesis. We aimed to identify the associations of genetic variations in the ZAP70, PTPN6, BANK1, and CLEC2D genes encoding for intracellular signaling molecules with IBDs. One hundred seven patients (39 CD and 68 UC) with IBD and 162 healthy control subjects from the Southern Tunisia were recruited. We genotyped 4 single-nucleotide polymorphisms (SNPs) in ZAP70 (rs1020396, rs11686881, rs13420683, and rs17695937), 2 SNPs in PTPN6 (rs7310161 and rs759052), 3 SNPs in BANK1 (rs10516487, rs17266594, and rs3733197), and 1 SNP in CLEC2D (rs3764021). ZAP70 displayed a strong genetic association with CD for rs13420683 [allele C, p=0.003, P(corr)=0.006, odds ratio (OR)=2.25 (1.32; 3.85); genotype CC, p=0.016, P(corr)=0.048, OR=2.57 (1.22; 5.41)]. However, in UC, a weak association with PTPN6 was observed [TT (p=0.01; P(corr)=0.03; OR=2.11 (1.18; 3.76)]. No significant association in the BANK1 and CLEC2D genes was observed. These results suggest the involvement of the ZAP70 and PTPN6 genes in the genetic component conferring a general susceptibility to CD and UC, respectively. This work provides motivation for studies aiming to replicate these findings in larger populations.

Type 1 diabetes (T1D) is an autoimmune disease (AID) with both genetic and environmental components. We aimed to investigate the genetic association of polymorphisms in genes previously linked with other AIDs, namely BANK1, IL15 and IL2/IL21 region. A total of 76 T1D patients and 162 controls from Southern Tunisia were recruited for a case-control association study investigating the relationship between sixteen SNPs of the BANK1, IL15 and IL2/IL21 gene region and T1D. In the BANK1 gene, G allele and GG genotype of rs3733197 were significantly increased in the group of T1D patients compared to controls. In addition, in the IL15 gene, the minor allele A of rs10519613 polymorphism was significantly higher in patients than in controls. No significant association was found for SNPS in IL2/IL21 gene region. The analysis of the haplotype structure revealed the G-C-A-C-T haplotype of the IL15 gene as associated with a reduction in the risk of developing T1D, while A-T-A-C-T haplotype increased the risk of developing the disease. Furthermore, in the IL2/IL21 region, only one haplotype consisting of eight SNPs was markedly associated with T1D susceptibility. Moreover, G-C combination of the BANK1/IL15 was significantly increased in T1D patients, compared to controls. Our results establish BANK1 and IL15 as new T1D genetic susceptibility factors and replicate the association of the 4q27 region with T1D. Our data agree with the effect previously observed for other autoimmune conditions and delineate a shared underlying mechanism.

Pemphigus is an autoimmune disorder resulting from the interaction between autoantibodies and desmoglein. Oxidative stress seems to be responsible for the onset/aggravation of many human diseases. Actually, it is considered as one of the several factors for the etiopathogenesis of pemphigus. The present study aims to evaluate the oxidative state in the sera of pemphigus vulgaris and pemphigus foliaceus patients by assessing lipid peroxidation, proteins oxidation, and antioxidant enzyme activity. This study included 36 pemphigus vulgaris and 42 pemphigus foliaceus patients as well as a group of controls consisting of 78 healthy volunteers. Malondialdehyde levels (p < 0.001) and catalase activity (p < 0.001) are higher in both groups of patients than in the control group. The two groups of patients showed a nonsignificant decrease in the thiol groups compared with the healthy one. A nonsignificant difference was shown between pemphigus vulgaris and pemphigus foliaceus patients, except for the catalase which shows an increase in the pemphigus vulgaris group. We have also found significant correlations between serum oxidative stress marker levels and serum anti-desmoglein antibody levels in the two pemphigus groups. These findings underline the implication of oxidative stress in the physiopathology of pemphigus by the increase in the autoantibodies’ reactivity.

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 x 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 lad. Accordingly, TNFa seem to contribute to the aethiopathogenesis of Tunisian endemic PF may be by the induction of a high TNFa production which is known to enhance the autoimmune cascade of the disease. (C) 2012 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

Autoimmune Polyglandular Syndrome Type II (APSII) is characterized by the co-occurrence of clinical insufficiency of at least two endocrine glands. Although, HLA determinants of APSII predisposition have been identified, little attention has been paid to non-HLA genes. Here, we used SNP genotyping in a Sequenom platform and genetic association tests to study a cohort of 60 APSII Tunisian patients presenting highly frequent co-occurrence of Autoimmune Thyroid Disease (AITD) and Type 1 Diabetes (T1D) and lower frequency of Addison’s disease (AD). We tested the high a priori possibility that well-established non-HLA autoimmunity loci were involved in APSII and confirmed five association signals to APSII, namely: (1) two T1D-associated SNPs, in CTLA4 and IL2RA, suggest their involvement in T1D pathogenesis in this cohort; (2) two SNPs in STAT4 and IL15 not previously associated to endocrinopathies, are possibly involved in co-occurrence of organ autoimmunity in APSII, and; (3) one SNP in TNF alpha showed association to APSII irrespective of AD. While this work was performed in a relatively small cohort, these results support the notion that the non-HLA genetic component of APSII include genetic factors specific of particular autoimmune manifestations as well as genetic factors that promote the co-occurrence of multiple autoimmune endocrinopathies.

The identification of susceptibility genes for inflammatory bowel disease (IBD) is key to understanding pathogenic mechanisms. Recently, the results of genetic association studies have highlighted many loci that are shared among several autoimmune diseases. We aimed to study the genetic epidemiology of polymorphisms in specific genes previously associated with other autoimmune diseases, namely the CREM, STAT4, STAT5a, Stat5b, and IRF5 genes. Twelve polymorphisms in the CREM, STAT4, STAT5a, Stat5b, and IRF5 genes were genotyped in a cohort of 107 IBD patients (39 Crohn's disease [CD] and 68 ulcerative colitis [UC]) and 162 controls from southern Tunisia. One CREM single nucleotide polymorphism (SNP) displayed evidence for genetic association with IBD (p = 8.7 × 10−4, odds ratio [OR] = 2.84 [1.58; 5.09]). One STAT4 SNP (p = 0.026; OR = 1.65 [1.06; 2.58]) exhibited a marginal association with UC but not with CD. No significant association was observed with the SNPs in STAT5a, IRF5, and STAT5b. These results suggest that common variants of the CREM gene are involved in the genetic component conferring general susceptibility to IBD, whereas STAT4 appears to be more specifically associated with UC. This work provides motivation for studies aiming to replicate these findings in larger populations.

The aim of our study was to evaluate the sensitivity, specificity and predictive values of isolated and combined ASCA and NANA assays in Tunisian inflammatory bowel diseases patients and to assess whether their presence is associated with particular clinical features of the disease.128 patients (39 with ulcerative colitis, 25 with Crohn disease, and 64 healthy subjects) were enrolled in the study. ASCA and NANA were performed by ELISA and indirect immuno-fluorescence, respectively. Sensitivity, specificity, PPV and NPV of NANA for UC was: 56.4%, 88%, 88% and 56.4%; and ASCA for CD were: 56%, 82.1%, 54.5% and 75.6%, respectively. The combined use of these two markers modified diagnostic accuracy: NANA+/ASCA- in UC 53.8%, 88%, 87.5% and 55% and for NANA-/ASCA+ in CD 52%, 94.9%, 86.7% and 75.5%. No significant association was found between the presence of a specific serological marker and patients' clinical features. In conclusion, the specificity of these combined markers tends to be higher than sensitivity, what made them more useful in the differentiation of the IBD subtypes rather than population screening.

UNLABELLED:The aim of our study was to evaluate the sensitivity, specificity and predictive values of isolated and combined ASCA and NANA assays in Tunisian inflammatory bowel diseases patients and to assess whether their presence is associated with particular clinical features of the disease.METHODS:128 patients (39 with ulcerative colitis, 25 with Crohn disease, and 64 healthy subjects) were enrolled in the study. ASCA and NANA were performed by ELISA and indirect immuno-fluorescence, respectively. Sensitivity, specificity, PPV and NPV of NANA for UC was: 56.4%, 88%, 88% and 56.4%; and ASCA for CD were: 56%, 82.1%, 54.5% and 75.6%, respectively. The combined use of these two markers modified diagnostic accuracy: NANA+/ASCA- in UC 53.8%, 88%, 87.5% and 55% and for NANA-/ASCA+ in CD 52%, 94.9%, 86.7% and 75.5%. No significant association was found between the presence of a specific serological marker and patients' clinical features. In conclusion, the specificity of these combined markers tends to be higher than sensitivity, what made them more useful in the differentiation of the IBD subtypes rather than population screening.

Pemphigus are rare but informative models of organ-specific autoimmune diseases, resulting from the interplay of environmental, genetic and stochastic factors. There are many arguments to consider that pemphigus have a genetic basis involving, as many other autoimmune diseases, several different genes with additive or synergistic effects. So far, the unique strategy used to identify the contributive loci has been direct analysis of candidate genes through conventional case-control association studies. The major histocompatibility complex in particular the class II locus was demonstrated to be associated with pemphigus with a high rate of replicability. The progresses in the understanding of pemphigus physiopathology and the development of new molecular tools offer new perspectives to unveiled the genetic basis of this group of autoimmune blistering diseases, as shown by recent studies of candidate genes expressed at different levels of the autoimmune process.

The interpretation of biological exam results requires the knowledge of physiological variation factors and reference values for every parameter. Following the preparation and the diffusion by the International Federation of Clinical Chemistry (IFCC) of a new reference material for the dosage of plasmatic proteins (CRM470) and in order to take part in the international effort of standardization of these dosages, we established reference ranges in the tunisian population for 9 plasmatic proteins: the Immunoglobulines G, A and M, complement factors C3 and C4, albumin, transferrin, haptoglobin and the a 1-glycoprotéin acid. Our sample of 211 healthy blood donors aged between 18 and 63 years. Reference limits 0.95 that we obtained are located within variation of most reference values lately found in the literature.