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1.
J Crit Care ; 81: 154533, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38359518

RESUMO

To investigate the potential regulatory effect of erythromycin added to standard care in septic patients on sepsis biomarkers and clinical outcome. It was a single-blind randomized trial including critical septic patients. The primary endpoint was the change in the TNF/IL-10 ratio between days 0 and 6. Changes in other biomarkers, vasopressor use, and 28-day mortality were secondary endpoints. One hundred and ten patients were examined (erythromycin group, n = 55 versus placebo group, n = 55). Clinical features of the groups were well matched. Erythromycin addition had no beneficial effects on the TNF/IL-10 ratio or mortality (51% vs. 47%, p = 0.62). Both groups' serum TNF/IL-10 ratios did not significantly rise (from 0.48 [0.34-1.18] to 0.59 [0.21-1.10] vs. 0.65 [0.25-1.14] to 0.93 [0.24-1.88] in the erythromycin and placebo groups, respectively; p values = 0.86 and 0.12). Serum Procalcitonin (PCT) and CRP dropped considerably in the Erythromycin group, whereas only PCT showed a drop in the placebo group. On day 6, the non-survivors' serum TNF/IL-10 ratio was lower than that of the survivors (0.55 [0.17-1.04] vs 1.08 [0.4-2.28], p = 0.029). Neither the pro/anti-inflammatory imbalance nor the mortality were impacted by the addition of erythromycin to standard care in septic patients (ClinicalTrials.gov ID: NCT04665089 (11/12/2020)).


Assuntos
Sepse , Choque Séptico , Humanos , Interleucina-10/uso terapêutico , Eritromicina/uso terapêutico , Método Simples-Cego , Biomarcadores , Pró-Calcitonina
2.
Tunis Med ; 101(6): 553-558, 2023 Jun 05.
Artigo em Francês | MEDLINE | ID: mdl-38372546

RESUMO

INTRODUCTION: Despite current recommendations, most asthmatics remain insufficiently controlled. This is largely due to non-adherence to medications. Looking for factors associated with lack of therapeutic adherence is mandatory in order to improve the management of these patients. AIM: To assess the degree of compliance in a population of Tunisian asthmatic patients and to identify the factors associated with poor compliance. METHODS: It was a cross-sectional study over a period of six months. Asthma control was assessed using the Asthma Control Test. Treatment compliance was specified using the Morisky questionnaire. Associations between adherence to treatment and certain patient characteristics were sought. RESULTS: During the study period, 165 adult patients were included (average age: 46.8 years±15.3 years; 114 women). The median duration of asthma evolution was 10.5 years [1-60 years]. Asthma was uncontrolled in 50% of the cases. Lack of treatment adherence was observed in 45% of patients. Compliance was better in women (p <0.05) and in patients with better socioeconomic status (p= 0.04). Patients with gastroesophageal reflux disease were also more observant (p=0.03); however, those with obesity were less (p> 0.05). In multivariate analysis, patients with good socioeconomic conditions (OR=4,516; IC95% [1.433-14.232]; p=0,01) and those with a previous a history of coronary artery disease (OR=15,37 ; IC95% [1.25-188.857] ; p=0.03) were more likely to have good adherence. CONCLUSION: Although it is a key element in the management of asthma, treatment compliance remains insufficient in Tunisian patients with asthma. Patient education is essential in order to correct the factors incriminated in uncontrolled asthma. The challenge remains to overcome the socioeconomic difficulties and the lack of access to treatment in our context.


Assuntos
Antiasmáticos , Asma , Adulto , Humanos , Feminino , Pessoa de Meia-Idade , Antiasmáticos/uso terapêutico , Estudos Transversais , Adesão à Medicação , Asma/terapia , Asma/tratamento farmacológico , Obesidade
3.
Front Immunol ; 13: 942417, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35990693

RESUMO

Rheumatoid arthritis (RA) is a systemic autoimmune disease during which fibroblast-like synoviocytes (FLS) contribute to both joint inflammation and destruction. FLS represent the core component of the synovial membrane. Following inflammation of this membrane, an effusion of cell-rich synovial fluid (SF) fills the joint cavity. Unlikely, SF has been shown to contain fibroblasts with some shared phenotypic traits with the synovial membrane FLS. These cells are called SF-FLS and their origin is still unclear. They are either brought into the synovium via migration through blood vessels, or they could originate within the synovium and exist in projections of the synovial membrane. SF-FLS function and phenotype are poorly documented compared to recently well-characterized synovial membrane FLS subsets. Furthermore, no study has yet reported a SF-FLS single-cell profiling analysis. This review will discuss the origin and cellular characteristics of SF-FLS in patients with RA. In addition, recent advances on the involvement of SF-FLS in the pathogenesis of RA will be summarized. Current knowledge on possible relationships between SF-FLS and other types of fibroblasts, including synovial membrane FLS, circulating fibrocytes, and pre- inflammatory mesenchymal (PRIME) cells will also be addressed. Finally, recent therapeutic strategies employed to specifically target SF-FLS in RA will be discussed.


Assuntos
Artrite Reumatoide , Sinoviócitos , Fibroblastos/patologia , Humanos , Inflamação/patologia , Líquido Sinovial , Sinoviócitos/patologia
5.
Front Immunol ; 12: 663683, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34211463

RESUMO

Background: Tissue derived fibroblast-like synoviocytes (td-FLS) are key actors in pannus formation and contribute to joint destruction and inflammation during rheumatoid arthritis (RA). Several members of the Wnt family, including Wnt5a, may contribute to RA td-FLS activation and can potentially serve as therapeutic targets. Objective: The present work aimed to investigate the expression of Wnt5a signaling elements in RA td-FLS and their potential precursors (fluid derived (fd) FLS and fibrocytes). We also studied the role of Wnt5a in RA td-FLS pro-inflammatory activity and whether the inhibitor SFRP5 could restore Wnt5a-induced synovial dysfunction in vitro. Materials and Methods: The levels of Wnt5a, SFRP5, Wnt5a receptors/coreceptors and Wnt5a pro-inflammatory targets were determined in cultured RA td-FLS, fd-FLS and fibrocytes using qPCR under basal conditions. The expression of pro-inflammatory molecules was assessed after RA td-FLS stimulation with Wnt5a and SFRP5 at different time points. Results: Our data showed that td-FLS, fd-FLS and fibrocytes from patients with RA expressed similar levels of Wnt5a and a set of Wnt5a receptors/coreceptors. We also demonstrated that Wnt5a stimulated the expression of the pro-inflammatory targets, especially IL1ß, IL8 and IL6 in RA td-FLS. Wnt5a-induced inflammation was enhanced in the presence of SFRP5. Furthermore, Wnt5a alone and in conjunction with SFRP5 inhibited the gene expression of TCF4 and the protein levels of the canonical coreceptor LRP5. Conclusion: Wnt5a pro-inflammatory effect is not inhibited but enhanced by SFRP5 in RA td-FLS. This research highlights the importance of carefully evaluating changes in Wnt5a response in the presence of SFRP5.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Artrite Reumatoide/etiologia , Artrite Reumatoide/metabolismo , Sinoviócitos/metabolismo , Proteína Wnt-5a/metabolismo , Idoso , Artrite Reumatoide/diagnóstico , Biomarcadores , Células Cultivadas , Suscetibilidade a Doenças , Feminino , Fibroblastos , Regulação da Expressão Gênica , Humanos , Imuno-Histoquímica , Mediadores da Inflamação/metabolismo , Masculino , Pessoa de Meia-Idade , Sinoviócitos/imunologia , Sinoviócitos/patologia , Via de Sinalização Wnt , Proteína Wnt-5a/genética
6.
Indian J Tuberc ; 68(2): 221-229, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33845956

RESUMO

BACKGROUND AND AIMS: Polymorphisms within genes encoding the cytokines involved in anti-tuberculosis immunity have been widely studied and sometimes associated with an increased risk of developing the active form of tuberculosis (TB). This study analyzes for the first time the impact of two polymorphisms, namely IFNG+874 T/A and IL10-1082 G/A, in the Algerian population where tuberculosis is moderately endemic. METHODS: This case-control study included 104 healthy controls and 141 active TB patients: 75 extrapulmonary (EPTB) and 66 pulmonary (PTB). They were all genotyped by refractory mutational system-PCR amplification. In order to measure the functional impact of IFNG+874 T/A on the production rate of IFN-γ, 43 patients performed a QuantiFERON®Gold In-tube test. RESULTS: The IFNG+874 AA genotype was associated with a higher risk of developing EPTB (OR = 2.52; 95%CI = 1.23-5.18; p = 0.012) while the IFNG+874 TA genotype was associated with a greater protection (OR = 0.34, 95%CI = 0.16-0.74; p = 0.006) which was further characterized by a high production of IFN-γ (p = 0.001). Similarly, the allele A of SNP IL10-1082 G/A, especially in its homozygous form (AA), were overrepresented in PTB patients (p = 0.010 and 0.019, respectively). The combination of both susceptibility genotypes (AA/AA) was strongly associated with risk of development of active TB (OR = 8.58; 95% C.I = 1.95-37.70, p = 0.004). This susceptibility combination was only significant in men regarding PTB (OR = 11.05; 95% C.I = 1.32-92.72, p = 0.027). Additionally, IFNG+874 TA and IL10-1082G∗ genotypes combination was mostly encountered in men controls and conferred the highest protection rate against EPTB (OR = 0.25; 95% C.I = 0.08-0.76, p = 0.015). CONCLUSION: These two cytokines genes polymorphisms are associated with active TB susceptibility in the Algerian population. They act synergistically in terms of protection and susceptibility regarding the two forms of the disease. Moreover, these associations were more marked among males suggesting a potential role of gender.


Assuntos
Predisposição Genética para Doença , Interferon gama/genética , Interleucina-10/genética , Tuberculose/genética , Adulto , Argélia , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Polimorfismo de Nucleotídeo Único , População Branca
7.
Connect Tissue Res ; 62(6): 720-731, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-33427511

RESUMO

Purpose: Fibroblast-like synoviocytes (FLS) represent one of the principal effectors of joint damage in rheumatoid arthritis (RA). Recent discovery of the circulating fibrocyte, a potential precursor of FLS, has raised issues regarding the characterization of fibrocytes with respect to their morphology and their biological role. In this study, we evaluated the morphology of fibrocytes in vitro and their ability to produce different extracellular matrix (ECM) components in comparison with two populations of RA FLS: synovial fluid FLS (fd-FLS) and intimal lining FLS (td-FLS). We also studied the expression of ECM regulators and a set of cytokine receptors involved in the pathogenesis of RA. Materials and Methods: Fibrocytes were cultured from peripheral blood of patients with RA. FLS were cultured from synovial fluids and tissues. ECM proteins (collagen I (col I) and fibronectin), Matrix metalloproteinases (MMP) (MMP3, and MMP9), ECM regulators (ß catenin, TCF4, and c-fos), and cytokine receptors (CXCR1, CXCR2, CXCR3, IL1RI, IL1RII, and IL6Rα) were analyzed using qRT-PCR and/or western blot. Results: Our results demonstrated that fibronectin and MMP3 levels were higher in FLS compared to fibrocytes. Although MMP9 was expressed in the three cell types, its level was greater in fibrocytes than in td/fd FLS. The three cell types expressed CXCR3, IL1RI, IL1RII, and IL6Rα, while the expression of CXCR1 and CXCR2 was restricted to fibrocytes. Conclusion: Our results demonstrated that fibrocytes express ECM molecules and cytokines receptors. The observed differences between fibrocytes and FLS may be due to their distinct functions or differentiation state during RA.Abbreviations: RA: Rheumatoid ArthritisFLS: fibroblast-like synoviocytestd: tissue derivedfd: fluid derivedSF: Synovial FluidWnt: WinglessMMP: Matrix MetalloproteinaseCIA: murine collagen induced arthritisECM: Extracellular matrixcol I: Collagen ITCF/LEF: T-cell factor/lymphoid enhancer-binding factorAP1: Activator Protein 1.


Assuntos
Artrite Reumatoide , Metaloproteinase 9 da Matriz , Animais , Artrite Reumatoide/patologia , Células Cultivadas , Colágeno/metabolismo , Matriz Extracelular/metabolismo , Fibroblastos/metabolismo , Fibronectinas/metabolismo , Humanos , Metaloproteinase 3 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Membrana Sinovial/patologia
8.
Nephrology (Carlton) ; 24(3): 357-364, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29292855

RESUMO

AIM: The aim of the present study was to characterize the molecular basis of complement factor I deficiency in Tunisian atypical haemolytic and uremic syndrome patients with low factor I levels. METHODS: Six adults and seven children were enrolled in this study. Complement factor I levels were assessed by a homemade sandwich ELISA and ranged between 12.5% and 60%. Genomic DNA was amplified by way of a polymerase chain reaction using intronic primers flanking the 13 coding exons. Sequencing of amplified products was carried out by the dye terminator sequencing method. Molecular study was performed on parental samples for three dead paediatric patients. The control group consisted of 100 healthy Tunisian donors. RESULTS: We identified a total of 13 substitutions and one insertion: seven in introns, four in exons and three in UTR. The new mutations were c.-132G > C, c.71 + 181 T > A in 5'UTR and intron 1, respectively. Three intronic polymorphisms were predicted to have impact on splicing events: c.482 + 6C > T, c.884-42_884-41insTTAAA (rs34422850) and c.1429 + 33 A > G (rs9998151). They were three missense mutations leading to a p.Ile 357Met, p.Ile416Leu and p.GLu548Gln. p.Ile 357Met was found in two patients and one relative. Half of the patients had associated mutation and/or polymorphisms. CONCLUSION: This is the first genetic study in Tunisian and Maghrebin atypical haemolytic and uraemic syndrome patients. The high occurrence of Ile357Met mutation may reflect a founding effect. Functional impact of the two new mutations c.-132G > C and c.71 + 181A > T have to be studied. Association of simultaneous genetic abnormalities may explain the variability of atypical haemolytic and uraemic syndrome, penetrance and disease phenotype.


Assuntos
Síndrome Hemolítico-Urêmica Atípica , Complemento C3/deficiência , Fator I do Complemento , Doenças Genéticas Inatas , Adulto , Síndrome Hemolítico-Urêmica Atípica/diagnóstico , Síndrome Hemolítico-Urêmica Atípica/epidemiologia , Síndrome Hemolítico-Urêmica Atípica/genética , Criança , Pré-Escolar , Estudos de Coortes , Complemento C3/genética , Fator I do Complemento/análise , Fator I do Complemento/genética , Feminino , Doenças Genéticas Inatas/sangue , Doenças Genéticas Inatas/epidemiologia , Doenças Genéticas Inatas/genética , Doenças da Deficiência Hereditária de Complemento , Humanos , Lactente , Masculino , Mutação , Polimorfismo Genético , Tunísia/epidemiologia
9.
Immunol Invest ; 46(3): 314-328, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28151034

RESUMO

CONTEXT: Fibroblast-like synoviocytes (FLS) from rheumatoid arthritis (RA) display pathogenic behavior. Various members of the Wnt pathway, especially the canonical Wnt/ß-catenin cascade, may contribute to autonomous RA FLS activation. It has been shown that the two Wnt inhibitors: sFRP3 and DKK1 contribute to several critical aspects of joint biology. However, their effects on RA FLS are poorly characterized. The aim of our study was to investigate the effects of sFRP3 and DKK1 on FLS markers, Wnt components, and target oncogenes expression by RA FLS and compare the findings to osteoarthritic (OA) FLS. MATERIALS AND METHODS: RA and OA FLS were treated with sFRP3 and DKK1 for 6 days. Wnt signaling components (Wnt5a, LRP5 and ß-catenin), Wnt target oncogenes (cyclin E1 and WISP1), and FLS markers (fibronectin and MMP3) were analyzed using western blotting and/or qRT-PCR. RESULTS: Our data indicated that sFRP3 down-regulated the key gene ß-catenin in RA FLS. sFRP3 decreased fibronectin, a well-known downstream effectors gene of Wnt/ß-catenin pathway, and LRP5 expression in both RA and OA FLS. In OA FLS, sFRP3 induced increased expression of Wnt5a and MMP3 but did not affect their levels in RA FLS. On the other hand, DKK1 increased fibronectin expression in RA FLS and decreased its expression in OA FLS. CONCLUSION: Our results confirm the involvement of Wnt signaling in FLS transformation and show that two inhibitors of the same cascade can regulate differently the same elements and that a single inhibitor can initiate signaling depending on cellular context. ABBREVIATIONS: FLS: fibroblast-like synoviocytes; RA: rheumatoid arthritis; Wnt: Wingless; Fz: frizzled; LRP: Fz/low-density lipoprotein receptor protein; WISP1: Wnt1 inducible signaling pathway protein 1; sFRP: secreted Fz-related proteins; DKK: Dickkopf; OA: osteoarthritis; DMEM: Dulbecco's modified Eagle's medium; FBS: fetal bovine serum; PBS: phosphate buffered saline; SDS-PAGE: sodium dodecyl sulfate-polyacrylamide gel electrophoresis; ECL: enhanced chemiluminescence detection solution; MMP3: metaloproteinase 3; qRT-PCR: quantitative real-time polymerase chain reaction; S.D: standard deviation; CRD: cysteine-rich domain; MeCP2: methyl-CpG-binding protein; RANKL: nuclear factor-kappa B ligand.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Artrite Reumatoide/imunologia , Fibroblastos/fisiologia , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Proteínas Musculares/metabolismo , Osteoartrite/imunologia , Sinoviócitos/fisiologia , Proteínas Wnt/metabolismo , Proliferação de Células , Células Cultivadas , Microambiente Celular , Feminino , Regulação da Expressão Gênica , Humanos , Masculino , Transdução de Sinais
11.
J Autoimmun ; 62: 39-44, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26119135

RESUMO

OBJECTIVE: Globally approximately 60 cases of C1q deficiency have been described with a high prevalence of Systemic Lupus Erythematosus (SLE). So far treatment has been guided by the clinical presentation rather than the underlying C1q deficiency. Recently, it was shown that C1q production can be restored by allogeneic hematopoietic stem cell transplantation. Current literature lacks information on disease progression and quality of life of C1q deficient persons which is of major importance to guide clinicians taking care of patients with this rare disease. METHODS: We performed an international survey, of clinicians treating C1q deficient patients. A high response rate of >70% of the contacted clinicians yielded information on 45 patients with C1q deficiency of which 25 are published. RESULTS: Follow-up data of 45 patients from 31 families was obtained for a median of 11 years after diagnosis. Of these patients 36 (80%) suffer from SLE, of which 16 suffer from SLE and infections, 5 (11%) suffer from infections only and 4 (9%) have no symptoms. In total 9 (20%) of the C1q deficient individuals had died. All except for one died before the age of 20 years. Estimated survival times suggest 20% case-fatality before the age of 20, and at least 50% of patients are expected to reach their middle ages. CONCLUSION: Here we report the largest phenotypic data set on C1q deficiency to date, revealing high variance; with high mortality but also a subset of patients with an excellent prognosis. Management of C1q deficiency requires a personalized approach.


Assuntos
Complemento C1q/deficiência , Complemento C1q/imunologia , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/imunologia , Fenótipo , Adolescente , Adulto , Idade de Início , Criança , Pré-Escolar , Complemento C1q/genética , Feminino , Humanos , Lactente , Recém-Nascido , Infecções/diagnóstico , Infecções/epidemiologia , Infecções/etiologia , Infecções/terapia , Estimativa de Kaplan-Meier , Lúpus Eritematoso Sistêmico/epidemiologia , Lúpus Eritematoso Sistêmico/genética , Lúpus Eritematoso Sistêmico/terapia , Masculino , Prognóstico , Qualidade de Vida , Inquéritos e Questionários , Resultado do Tratamento , Adulto Jovem
12.
Artigo em Inglês | MEDLINE | ID: mdl-25111364

RESUMO

The authors aimed to determine the prevalence of antineuronal antibodies in 103 psychiatric inpatients and 41 control subjects with no history of malignancies or neurological disorders. All sera were tested by indirect immunofluorescence and positive sera by immunoblot. Using immunofluorescence, antineuronal nuclear autoantibodies were detected in 20 patients and none of the control subjects, and antibodies reacted with the cytoplasm of Purkinje cells in six patients and two control subjects. The immunoblot confirmed well-characterized antineuronal antibodies only in five patients: two had anti-Ri and three had anti-Yo antibodies. After a follow-up of 5 years, none of these patients developed neurological disorder or malignancy.


Assuntos
Anticorpos Antinucleares/sangue , Autoanticorpos/sangue , Transtornos Mentais/sangue , Transtornos Mentais/epidemiologia , Adulto , Idoso , Distribuição de Qui-Quadrado , Feminino , Humanos , Pacientes Internados/estatística & dados numéricos , Estudos Longitudinais , Masculino , Transtornos Mentais/classificação , Pessoa de Meia-Idade , Tunísia/epidemiologia
14.
Immunol Invest ; 42(4): 356-68, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23883201

RESUMO

This work aims to estimate celiac disease prevalence in school-children in the island of Djerba and assess rapid method feasibility for screening. We screened 2064 schoolchildren by a rapid method to detect IgA anti-tissue transglutaminase and IgA deficiency. Children with positive results were tested for IgA anti-transglutaminase and anti-endomysium by conventional tests. In positive children, intestinal biopsy was performed. IgA deficiency suspected by rapid method was confirmed by nephelometry. In these cases IgG anti-endomysium was performed. Rapid test was positive in 7 children; conventional serology was positive in all and 6 of them accepted the biopsy. Total villous atrophy was observed in 5 while intestinal mucosa was normal in one. Among children with positive serology, 3 had silent form, 1 chronic diarrhea, one growth failure and 2 had borderline growth. IgA deficiency was suspected in 13 cases and was confirmed in 11 children tested. Prevalence of celiac disease was 0.24-0.34% and that of IgA deficiency 0.5-0.6%. This screening study confirms that celiac disease is relatively common in schoolchildren in Tunisia. It confirms also that even those with symptoms typical for celiac disease escape diagnosis. Rapid test is better accepted by parents and children than test requiring a venous blood sample.


Assuntos
Doença Celíaca/diagnóstico , Imunoglobulina A/sangue , Transglutaminases/imunologia , Biópsia , Doença Celíaca/sangue , Doença Celíaca/epidemiologia , Criança , Feminino , Humanos , Deficiência de IgA/sangue , Deficiência de IgA/diagnóstico , Deficiência de IgA/epidemiologia , Mucosa Intestinal/patologia , Masculino , Prevalência , Tunísia/epidemiologia
15.
Exp Diabetes Res ; 2011: 964160, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21461382

RESUMO

We aimed to characterize the different subgroups of ketosis-prone diabetes (KPD) in a sample of Tunisian patients using the Aß scheme based on the presence or absence of ß-cell autoantibodies (A+ or A-) and ß-cell functional reserve (ß+ or ß-) and we investigated whether HLA class II alleles could contribute to distinct KPD phenotypes. We enrolled 43 adult patients with a first episode of ketosis. For all patients we evaluated clinical parameters, ß-cell autoimmunity, ß-cell function and HLA class II alleles. Frequency distribution of the 4 subgroups was 23.3% A+ß-, 23.3% A-ß-, 11.6% A+ß+ and 41.9% A-ß+. Patients from the group A+ß- were significantly younger than those from the group A-ß- (P = .002). HLA susceptibility markers were significantly more frequent in patients with autoantibodies (P = .003). These patients also had resistance alleles but they were more frequent in A+ß+ than A+ß- patients (P = .04). Insulin requirement was not associated to the presence or the absence of HLA susceptibility markers. HLA class II alleles associated with susceptibility to autoimmune diabetes have not allowed us to further define Tunisian KPD groups. However, high prevalence of HLA resistance alleles in our patients may reflect a particular genetic background of Tunisian KPD population.


Assuntos
Diabetes Mellitus Tipo 1/genética , Cetoacidose Diabética/genética , Antígenos HLA-DQ/genética , Antígenos HLA-DR/genética , Adulto , Autoanticorpos/sangue , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 1/imunologia , Diabetes Mellitus Tipo 1/metabolismo , Cetoacidose Diabética/epidemiologia , Cetoacidose Diabética/imunologia , Cetoacidose Diabética/metabolismo , Feminino , Frequência do Gene , Marcadores Genéticos , Genótipo , Antígenos HLA-DQ/imunologia , Cadeias beta de HLA-DQ , Antígenos HLA-DR/imunologia , Cadeias HLA-DRB1 , Humanos , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/imunologia , Células Secretoras de Insulina/metabolismo , Masculino , Pessoa de Meia-Idade , Fenótipo , Estudos Prospectivos , Tunísia/epidemiologia
16.
Tunis Med ; 89(1): 16-7, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21267821

RESUMO

AIM: To evaluate a new whole blood rapid test for the detection of IgA anti-transglutaminase (ATG) for diagnosis and diet survey of celiac disease (CD). METHODS: 57 children, 20 of them were CD patients on a gluten-free diet and 37 were under suspicion of CD were enrolled. IgAATG was detected by the conventional ELISA test and the new rapid whole blood test. RESULTS: Concordance between the 2 tests was 96.4%. All patients positive with ELISA were also positive by the rapid test. Only 2 patients were slightly positive by the rapid test and negative by ELISA. CONCLUSION: Whole blood rapid test seems to be as performant as ELISA test for IgAATG detection.


Assuntos
Doença Celíaca/diagnóstico , Testes Sorológicos , Adolescente , Autoanticorpos/sangue , Criança , Pré-Escolar , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunoglobulina A/imunologia , Lactente , Masculino , Valor Preditivo dos Testes , Sensibilidade e Especificidade
17.
Tunis Med ; 88(4): 269-76, 2010 Apr.
Artigo em Francês | MEDLINE | ID: mdl-20446263

RESUMO

BACKGROUND: The complement system is one of the main effectors of both innate and adaptive immunity. Hereditary complement deficiency, mainly those of the terminal pathway (C5-C9), is at increased risk for septic meningitides particularly meningococcal ones. AIM: to assess clinical and biochemical features of 3 Tunisian adults with C5 hereditary complement deficiency (C5D), with a familial study performed for two of them. METHODS: Functional activity of the classical and the alternative pathway of complement (CH50 and AP50 respectively) were measured according to standards haemolytic procedures. Serum concentration of complement components were determined by nephelemetry and ELISA. C5D was diagnosed when CH50, AP50 and C5 antigenic level were highly decreased. RESULTS: Our patients were 2 men and one woman. All these patients presented clinical symptoms of septic meningitides. Meningococcal orign was confirmed in one case. C5 level varies between 0 and 0.4%. Levels of other complement components: Clq, C3, C4, properdine, C6, C8 and C9 were normal. Antigenic C7 level was 50% in the female patient. Familial study revealed no similar hereditary complement deficiency in relatives. CONCLUSION: Only 27 cases with C5D were reported in the literature. The description of 3 cases in our series demonstrates that: * C5D is not rare in Tunisia, ** C5D is clinically commonly complicated by meningitides with unconstant severity, *** C5D is biologically caracterised by a variable level of the plasmatic C5 component.


Assuntos
Complemento C5/deficiência , Adulto , Feminino , Humanos , Síndromes de Imunodeficiência/genética , Masculino , Meningite Meningocócica/diagnóstico , Tunísia
18.
Eur J Gastroenterol Hepatol ; 21(11): 1286-90, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19474744

RESUMO

OBJECTIVE: To elucidate the HLA DRB1, DQB1 and DQA1 polymorphism in Tunisian children with typical form of coeliac disease (CD) in comparison with those from mass screening (atypical and silent CD). MATERIALS AND METHODS: We recruited three groups: group I: 40 CD children diagnosed according to the ESPGHAN criteria. group II: 40 healthy controls matched with sex, age and geographic origin. group III: 38 CD children coming from mass screening in schoolchildren. HLA class II DRB1, DQB1 and DQA1 alleles were typed by PCR-sequence-specific primer. RESULTS: Comparing the groups I and II, we found a pronounced increase of the susceptible alleles HLA DRB1*03 (relative risk, RR = 4.18, Pc = 0.001), DQB1*02 (RR = 7.9, Pc<0.0001) and DQA1*0501 (RR = 4.1, Pc = 0.001). As for protective alleles, we detected a high frequency of DRB1*13 (RR = 0.059, Pc = 0.001), DQA1*0102 (RR = 0.071, Pc = 0.009) and DQB1*06 (RR = 0.125, Pc = 0.0042). Haplotype analysis showed that the main combination observed was the conformation of DQ2 (DQA1*0501-DQB1*02) in 36 patients from group I and 30 from group III. There was no statistically significant difference between the groups I and III according to the distribution of the different alleles. CONCLUSION: We confirmed in this study the high frequency of DQ2 haplotype in CD patients and we identified new protective alleles DRB1*13, DQA1*0102 and DQB1*06. However, HLA polymorphism seems to have no evident impact on clinical outcome of CD.


Assuntos
Doença Celíaca/genética , Antígenos HLA-D/genética , Estudos de Casos e Controles , Doença Celíaca/complicações , Criança , Diarreia/etiologia , Feminino , Predisposição Genética para Doença , Transtornos do Crescimento/etiologia , Antígenos HLA-DQ/genética , Cadeias alfa de HLA-DQ , Cadeias beta de HLA-DQ , Antígenos HLA-DR/genética , Cadeias HLA-DRB1 , Haplótipos , Teste de Histocompatibilidade , Humanos , Masculino , Polimorfismo Genético
19.
Expert Rev Clin Immunol ; 4(5): 629-37, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20476965

RESUMO

The involvement of the complement system in the pathogenesis of autoimmune diseases is a matter of debate. However, the link between complement abnormalities and systemic lupus erythematosus (SLE) is well established and widely described. Homozygous and/or heterozygous complement-component deficiencies of the classical pathway (C1q, C1r, C1s, C4A, C4B and C2) are causally associated with susceptibility to the development of SLE. Although the severity of the disease and the strength of the association are heterogeneous for deficiencies of these proteins, they commonly cause peculiar SLE syndromes with an early age of onset, a susceptibility to bacterial infections and negative anti-dsDNA antibodies. In this review, we highlight the available data on complement deficiency and SLE with a focus on deficiencies in classical complement pathway components. We also discuss the paradox of the link between complement deficiency and lupus. The complement system acts as a 'friend' through the clearance of immune complexes and apoptotic cells, which explains the close association between complement deficiency and lupus. It also acts as an 'enemy' by participating in the effector inflammatory phase of the autoimmune response. Understanding the importance of complement deficiencies should provide novel targets for therapeutic interventions in the modulation of the immune response.

20.
Ann N Y Acad Sci ; 1107: 356-62, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17804563

RESUMO

As an autoimmune disease, type 1 diabetes mellitus (T1DM) is characterized by the presence of several autoantibodies. The aim of this study was to examine a broad spectrum of antibodies in Tunisian adult T1DM and to compare their prevalence with a healthy control group. Two hundred sixty-one diabetics and 100 healthy blood donors were enrolled in this study. Indirect immunofluorescence was performed for the detection of islet cell, antiendomysial, antinuclear, antimitochondrial, antismooth muscle, antireticulin, and antikeratin antibodies. Enzyme-linked immunosorbent assay was used for measuring anticardiolipin, antigliadin, antitransglutaminase, and antithyroperoxidase antibodies. Latex agglutination was used for the detection of rheumatoid factors. As expected, islet cell antibodies were the most frequent (33.7%). Antigliadin, antithyroperoxidase, and antikeratin antibodies were relatively frequent (18%, 15.3%, and 10.3%, respectively) and were statistically more prevalent in diabetics than in controls. There was no correlation between diabetes duration and any autoantibody, except for islet cell antibodies that were more frequent at the onset of diabetes. Several autoantibodies nonspecific of diabetes are frequent in diabetic patients, which may be associated with or predictors of some autoimmune diseases, and can also reflect a special profile of autoimmunity in diabetics in comparison to healthy controls.


Assuntos
Autoanticorpos/imunologia , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 1/imunologia , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tunísia/epidemiologia
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