Expression of extracellular matrix components and cytokine receptors in human fibrocytes during rheumatoid arthritis.

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.

Molecular basis of complement factor I deficiency in Tunisian atypical haemolytic and uraemic syndrome patients.

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.

sFRP3 and DKK1 Regulate Fibroblast-Like Synoviocytes Markers and Wnt Elements Expression Depending on Cellular Context.

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.

Marked variability in clinical presentation and outcome of patients with C1q immunodeficiency.

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.

High prevalence of antineuronal antibodies in Tunisian psychiatric inpatients.

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.

Immunologic effect and clinical impact of erythromycin in septic patients: A randomized clinical trial.

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)).

TubIAgnosis: A machine learning-based web application for active tuberculosis diagnosis using complete blood count data.

Objective: Tuberculosis remains a major global health challenge, with delayed diagnosis contributing to increased transmission and disease burden. While microbiological tests are the gold standard for confirming active tuberculosis, many cases lack microbiological evidence, necessitating additional clinical and laboratory data for diagnosis. The complete blood count (CBC), an inexpensive and widely available test, could provide a valuable tool for tuberculosis diagnosis by analyzing disturbances in blood parameters. This study aimed to develop and evaluate a machine learning (ML)-based web application, TubIAgnosis, for diagnosing active tuberculosis using CBC data. Methods: We conducted a retrospective case-control study using data from 449 tuberculosis patients and 1200 healthy controls in Oran, Algeria, from January 2016 to April 2023. Eight ML algorithms were trained on 18 CBC parameters and demographic data. Model performance was evaluated using balanced accuracy, sensitivity, specificity, positive predictive value, negative predictive value, and area under the receiver operating characteristic curve (AUC). Results: The best-performing model, Extreme Gradient Boosting (XGB), achieved a balanced accuracy of 83.3%, AUC of 89.4%, sensitivity of 83.3%, and specificity of 83.3% on the testing dataset. Platelet-to-lymphocyte ratio was the most influential parameter in this ML predictive model. The best performing model (XGB) was made available online as a web application called TubIAgnosis, which is available free of charge at https://yh5f0z-ghermi-mohamed.shinyapps.io/TubIAgnosis/. Conclusions: TubIAgnosis, a ML-based web application utilizing CBC data, demonstrated promising performance for diagnosing active tuberculosis. This accessible and cost-effective tool could complement existing diagnostic methods, particularly in resource-limited settings. Prospective studies are warranted to further validate and refine this approach.

Celiac disease in Tunisian children: a second screening study using a "new generation" rapid test.

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.

Factors influencing therapeutic adherence in Tunisian adults with asthma.

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.

The synovial fluid fibroblast-like synoviocyte: A long-neglected piece in the puzzle of rheumatoid arthritis pathogenesis.

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.

Is the rapid whole blood test useful for diagnosis and monitoring celiac disease in children?

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.

SFRP5 Enhances Wnt5a Induced-Inflammation in Rheumatoid Arthritis Fibroblast-Like Synoviocytes.

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.

Interferon-γ (+874 T/A) and interleukin-10 (-1082 G/A) genes polymorphisms are associated with active tuberculosis in the Algerian population of Oran's city.

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.

[Hereditary complement C5 deficiency: study of 3 Tunisian adult cases and literature review]. / Deficit héréditaire en protéine C5 du complément: etude de 3 cas tunisiens de l'adulte et revue de la littérature.

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.

Spectrum of autoantibodies in Tunisian adult type 1 diabetes mellitus.

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.

Hereditary complement deficiency and lupus: report of four Tunisian cases.

The aim of the study was to assess the clinical and immunological profile of lupus erythematosus (LE) patients with inherited complement deficiency (ICD). A laboratory-based study was conducted in which all LE patients with hypocomplementemia were included. ICD was assessed by hemolytic and antigenic assays. Type I C2 deficiency was assessed by polymerase chain reaction (PCR). ICD was diagnosed in four cases. In three systemic LE patients, ICD were: homozygous C2 deficiency in the first case, heterozygous C2 deficiency in the second, and homozygous C1q deficiency in the third case. In a discoid LE patient, a combined homozygous C2 and C6 deficiency was diagnosed. Almost all of our patients presented the classical clinical and immunological features of LE associated with ICD. Severe lupus with renal involvement and recurrent infections was present in half of the patients suggesting that these patients are prone to a serious management.

Pediatric systemic lupus erythematosus with C1q deficiency.

Hereditary deficiency of each component of the classical pathway is associated with increased susceptibility to lupus erythematosus (LE). Both the severity of the disease and the strength of this association are greatest for homozygous C1q deficiency, which is extremely rare. In fact, more than 90% of all individuals with deficiency of this component have LE. We report a 3-year-old female infant with history of discoid LE treated with topical corticosteroids for 1 year. She was referred to pediatric department for an exacerbation and extension of cutaneous lesions toward front-arm, hands, legs and feet, a glomerulonephritis, and thrombopenia. Immunologic tests revealed a positive speckled antinuclear antibody at 1/1600 with positive anti-Sm, anti-SSA, and anti-RNP antibodies. Test for anti-DNA was negative. These findings were compatible with a transition to a systemic form of lupus. Systemic corticosteroid treatment was started; however, the patient died by a severe digestive hemorrhage. Hemolytic complement activity (CH50) was undetectable in serum despite normal levels of C3 and C4 suggesting a deficiency of an early component of the complement cascade. Measurement of hemolytic assay for C1 functional activity was less than 1%. C1q deficiency was confirmed by a double immunodiffusion and ELISA using sheep polyclonal anti-C1q antibodies. C1q deficiency is a rare genetic disorder. Thirty-eight of the 41 patients reported to date have developed systemic LE. C1q deficiency may cause systemic LE via a critical role of this component in the physiological clearance of apoptotic cells.

Prevalence of celiac disease in Tunisia: mass-screening study in schoolchildren.

BACKGROUND: Celiac disease is reported to be common among North Africans, particularly Tunisians. Nevertheless, the prevalence of coeliac disease in the general population has not been previously investigated. OBJECTIVE: This study aimed to determine the prevalence of celiac disease among children in Tunisia and to describe the clinical profile of the screened patients. METHODS: A mass screening study based on drawing lots was carried out on schoolchildren in Ariana, a Tunisian district. A participation agreement was obtained from 6286 children (3175 boys, age: 9.7+/-3 years). Two children of known celiac disease were present in this population. All participants were tested for IgA antitissue transglutaminase antibodies (IgA-tTG) by a commercial enzyme-linked immunosorbent assay (ELISA) and total IgA levels. Sera, found positive by the initial screening, were assessed by immunofluorescence for the presence of IgA antiendomysium antibodies (IgA-AE). Positive participants were also called in for serological control, intestinal biopsy, biological exploration (hemoglobin rate, calcemia and albuminemia) and bone mineral densitometry. RESULTS: Among the 6284 participants, 139 (1/45) were positive for IgA-tTG. Forty-two of these had low-level IgA-tTG and no one had IgA deficiency. IgA-AE was detected in 40 participants. One hundred and seven children were called in, 28 had both positive tests (IgA-tTG +/IgA-AE+) and 79 were only positive for IgA-tTG (IgA-tTG +/IgA-AE-). Intestinal biopsy was performed in the 28 participants of the first group (IgA-tTG +/IgA-AE+) and confirmed celiac disease in 26 cases. In the second group (IgA-tTG +/IgA-AE-), intestinal biopsy was performed in 26 children and histological examination was normal in all cases. Among the 26 biopsy-proven celiac disease children, six (23%) had typical clinical symptoms of celiac disease, whereas the others had atypical forms with 11 (42%) asymptomatic. In 23 biopsy-proven celiac disease children, bone mineral density was significantly lower than that of a group of 109 normal children (0.850+/-0.06 g/cm2 versus 0.912+/-0.06 g/cm2, P<0.05). Seven participants (30.4%) among the celiac disease children and six (7.5%) among the controls had a total-body Z score for bone mineral density of <-2 (P<0.001). CONCLUSION: The prevalence of celiac disease in Tunisian schoolchildren, estimated to be about 1/157, is close to the European prevalence. Most of the screened children showed an atypical and asymptomatic form, but even the typical forms were underdiagnosed. Ostopenia was frequently observed in celiac disease patients.