Biclonal Gammopathies in South Tunisia: Clinical and Biological Characteristics.

OBJECTIVE: Biclonal 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. METHODS: We conducted a 31-year retrospective study including patients with persistent double monoclonal bands based on the results of immunofixation/immunoelectrophoresis. RESULTS: A total of 35 patients with available clinical data (sex ratio, M/F = 1.53; mean age, 70 ±â€…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. CONCLUSION: BGs 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.

Role of Serum Amyloid A as a Biomarker for Predicting the Severity and Prognosis of COVID-19.

Objective: To detect biomarkers that can be used to predict COVID-19 severity to identify patients with high probability of disease progression and poor prognosis. Methods: Of the 102 patients with confirmed COVID-19 who were admitted to King Fahd General Hospital, Jeddah City, Saudi Arabia, from July 1, 2021 to August 5, 2021, 50 were included in this cross-sectional study to investigate the influence of serum amyloid A (SAA) on disease severity and survival outcomes of COVID-19 patients. Dynamic shifts in SAA, C-reactive protein (CRP), white blood cell (WBC), lymphocytes, neutrophils, biochemical markers, and disease progression were examined. At admission, and at three, five, and seven days after treatment, at least four data samples were collected from all patients, and they underwent clinical status assessments. Results: Critically ill patients showed higher SAA and CRP levels and WBC and neutrophil counts and significantly lower lymphocyte and eosinophil counts compared to the moderately/severely ill patients, especially with regard to disease progression. Similarly, nonsurvivors had higher SAA levels than survivors. The moderately/severely ill patients and the survivors had significantly higher dynamic changes in SAA compared to the critically ill patients and nonsurvivors, respectively, with differences clearly noticed on the fifth and seventh day of treatment. ROC curve analysis revealed that the combination of SAA and CRP was valuable in evaluating the disease progression and prognosis of COVID-19 patients at different time points; however, a combination of SAA and lymphocyte counts was more sensitive for disease severity prediction on admission. The most sensitive parameters for predicting survival on admission were the combination of SAA/WBC and SAA/neutrophil count. Conclusions: The study findings indicate that SAA can be used as a sensitive indicator to assess the degree of disease severity and survival outcomes of COVID-19 patients.

Association of ZAP70 and PTPN6, but Not BANK1 or CLEC2D, with inflammatory bowel disease in the Tunisian population.

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.

Catalase and lipid peroxidation values in serum of Tunisian patients with pemphigus vulgaris and foliaceus.

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.

Non-HLA autoimmunity genetic factors contributing to Autoimmune Polyglandular Syndrome type II in Tunisian patients.

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 CREM gene is involved in genetic predisposition to inflammatory bowel disease in the Tunisian population.

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.

Diagnostic value and clinical significance of serological markers in Tunisian patients with inflammatory bowel diseases.

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.

Genetic factors in pemphigus.

Epidemiological studies performed in different ethnic populations and family studies, notably based on a partial phenotype of the autoimmune process, indicate that genetic factors are involved in the occurrence of pemphigus. However, the precise heritability remains uncertain in the absence of twin concordance rate studies. Among the different strategies available to identify genetic factors participating in autoimmune disease susceptibility, only population studies based on case-control design have been performed in pemphigus. These studies consistently showed that MHC locus, in particular HLA class II alleles, are associated with pemphigus vulgaris and pemphigus foliaceus. Other genes of the MHC locus may also participate in disease susceptibility as shown by studies using microsatellite markers across different regions of the MHC. It is likely that other non-MHC genes are involved in the pathogenesis of pemphigus. In particular, involvement of a polymorphic variant of desmoglein 1 gene was shown to be associated with pemphigus foliaceus and to interact in an epistatic manner with MHC class II genes to contribute to the autoimmune process. Other candidate genes to which a role can be assigned in the disease pathogenesis should be considered to design case-control or family-based association studies. Genome scan studies which require a large number of multiplex families to reach statistical power, should also be considered in the endemic form of pemphigus foliaceus because of the high number of familial cases.

[Reference ranges of 9 plasmatic proteins in Tunisian population based on the new IFCC reference material CRM 470]. / Approche pour l'etablissement des valeurs de reference (variations normales) dans la population Tunisienne de 9 proteines plasmatiques en se basant sur le materiau de reference CRM470 de l'IFCC.

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.