Lilia Laadhar

Spectrum of Autoantibodies in Tunisian Psychiatric Inpatients

One hundred and three psychiatric inpatients (74 men) were assessed for a wide spectrum of autoantibodies including antinuclear, antismooth muscle, antimitochondrial, antiDNA, anti-phospholipid, anti-cardiolipin IgG and IgM, antikeratin, rheumatoid factor, antithyroperoxydase, antigliadin IgA and IgG, antitransgutaminase, and antiendomysium antibodies. Four groups of patients were considered separately, including 47 with schizophrenia, 23 with schizoaffective disorder, 16 with bipolar disorder and 17 patients with other different psychiatric diagnosis. Forty one healthy, age- and sex-matched blood donors were used as a control group. There were no significant difference in the prevalence of the different autoantibodies between patients (N = 103) and controls except for antigliadin IgG (30.1 vs 9.8 respectively, p = 0.01). Presence of autoantibodies was influenced by age but not by sex or treatment. As for diagnosis categories, patients with bipolar disorder presented significantly more autoantibodies than the three other categories and controls. These results point out a possible autoimmune activation in at least a subgroup of psychiatric patients especially amongst those suffering from bipolar disorder.

WNT signaling and chondrocytes: from cell fate determination to osteoarthritis physiopathology

Abstract Context: Osteoarthritis (OA) is an articular disorder leading to the degradation of articular cartilage phenotypical chondrocytes modifications, including the acquisition of a fibroblast-like morphology, decreased expression of collagen type II, and increased expression of fetal collagen type I, metalloproteinase 13 and nitric oxide synthase. This promotes matrix degradation and unsuccessful cartilage repair. WNT signaling constitutes one of the most critical biological processes during cell fate assignment and homeostasis. Objectives: This review aims to give an insight on results from the studies that were interested in the involvement of WNT in OA. Methods: Studies were selected through a pubmed search. Results: Recent genetic data showed that aberration in WNT signaling may be involved in OA. WNT signals are transduced through at least three cascades: the canonical WNT/β-catenin pathway, the WNT/Ca2+ pathway and the WNT/planar cell polarity pathway. Most of the studies used in-vitro models to elucidate the involvement of WNT in the physiopathology of OA. These studies analyzed the expression pattern of WNT pathway components during OA such as WNT5, WNT7, co-receptor LRP, β-catenin, WNT target genes (c-jun, cyclins) and/or the interaction of these components with the secretion of OA most important markers such as IL-1, collagens, MMPs. Results from these studies are in favor of a deep involvement of the WNT signaling in the physiopathology of OA either by having a protective or a destructive role. Conclusion: Deeper researches may eventually allow scientists to target WNT pathway in order to help develop efficient therapeutic approaches to treat OA.

Pediatric systemic lupus erythematosus with C1q deficiency.

Abstract:  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.

The roles of canonical and non-canonical Wnt signaling in human de-differentiated articular chondrocytes

Abstract Osteoarthritis is the most prevalent form of arthritis in the world and it is becoming a major public health problem. Osteoarthritic chondrocytes undergo morphological and biochemical changes that lead to de-differentiation. The involvement of signaling pathways, such as the Wnt pathway, during cartilage pathology has been reported. Wnt signaling regulates critical biological processes. Wnt signals are transduced through at least three intracellular signaling pathways including the canonical Wnt/β-catenin pathway, the Wnt/Ca2 + pathway and the Wnt/planar cell polarity pathway. We investigated the involvement of the Wnt canonical and non-canonical pathways in human articular chondrocyte de-differentiation in vitro. Human articular chondrocytes were cultured through four passages with no treatment, or with sFRP3 treatment, an inhibitor of Wnt pathways, or with DKK1 treatment, an inhibitor of the canonical pathway. Chondrocyte-secreted markers and Wnt pathway components were analyzed using western blotting and qPCR. Inhibition of the Wnt pathway showed that the canonical Wnt signaling probably is responsible for inhibition of collagen II expression, activation of metalloproteinase 13 expression and regulation of Wnt7a and c-jun expression during chondrocyte de-differentiation in vitro. Our results also suggest that expressions of eNOS, Wnt5a and cyclinE1 are regulated by non-canonical Wnt signaling.

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

Abstract:  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.

The role of the Notch pathway in healthy and osteoarthritic articular cartilage: from experimental models to ex vivo studies

Osteoarthritis is the most prevalent form of arthritis in the world. With the progressive ageing of the population, it is becoming a major public health problem. The involvement of certain signaling pathways, such as the Notch pathway, during cartilage pathology has been reported. In this review, we report on studies that investigated the expression pattern of the Notch family members in articular cartilage and the eventual involvement of this pathway in the modulation of the physiology and pathology of chondrocytes. Temporal and/or spatial modulation of this signaling pathway may help these cells to synthesize a new functional extracellular matrix and restore the functional properties of the articular cartilage.

Notch signaling is involved in human articular chondrocytes de-differentiation during osteoarthritis.

Abstract Context: During osteoarthritis (OA), chondrocytes undergo de-differentiation, resulting in the acquisition of a fibroblast-like morphology, decreased expression of collagen type II (colII) and aggrecan, and increased expression of collagen type I (colI), metalloproteinase 13 (MMP13) and nitric oxide synthase (eNOS). Notch signaling plays a crucial role during embryogenesis. Several studies showed that Notch is expressed in adulthood. Objective: The aim of our study was to confirm the involvement of Notch signaling in human OA at in vitro and ex vivo levels. Materials and methods: Normal human articular chondrocytes were cultured during four passages either treated or not with a Notch inhibitor: DAPT. Human OA cartilage was cultured with DAPT for five days. Chondrocytes secreted markers and some Notch pathway components were analyzed using Western blotting and qPCR. Results: Passaging chondrocytes induced a decrease in the cartilage markers: colII and aggrecan. DAPT-treated chondrocytes and OA cartilage showed a significant increase in healthy cartilage markers. De-differentiation markers, colI, MMP13 and eNOS, were significantly reduced in DAPT-treated chondrocytes and OA cartilage. Notch1 expression was proportional to colI, MMP13 and eNOS expression and inversely proportional to colII and aggrecan expression in nontreated cultured chondrocytes. Notch ligand: Jagged1 increased in chondrocytes culture. DAPT treatment resulted in reduced Jagged1 expression. Notch target gene HES1 increased during chondrocyte culture and was reduced when treated with DAPT. Conclusion: Targeting Notch signaling during OA might lead to the restitution of the typical chondrocyte phenotype and even to chondrocyte redifferentiation during the pathology.

Prevalence of Anticardiolipin and Anti-β2-Glycoprotein I Antibodies in Celiac Disease

The aim of this study was to evaluate the prevalence of anticardiolipin antibodies (aCL) and anti-β2-glycoprotein I antibodies (aβ2GPI) in patients with celiac disease and to analyze the clinical features of antiphospholipid syndrome in these patients. We conducted a prospective case-control study based on the evaluation of IgG, IgM and IgA aCL, and IgG and IgA aβ2GPI in celiac disease patients and in controls. All patients were asked about any occurrence of thrombotic manifestations. In addition, women were asked about pregnancy morbidity. Fifty celiac disease patients and 50 healthy controls were studied. IgM aCL were not detected in study group or in controls. IgG aCL were found in two patients and in one control. IgA aCL were significantly more frequent in celiac disease patients compared with controls (13/50 (26%) vs. 2/50 (4%), p=0.004, OR [95% CI]=9.09 [1.81–50]). There was no statistically significant difference for the prevalence of IgG and IgA aβ2GPI between patients and controls. Clinical features of antiphospholipid syndrome were noted in two patients with negative antibodies. Prevalence of IgM and IgG aCL and of aβ2GPI were not increased in celiac disease. IgA aCL were more frequently detected in celiac disease. However, no clinical features of antiphospholipid syndrome were noted.

Synovial fluid and serum levels of IL-17, IL-23, and CCL-20 in rheumatoid arthritis and psoriatic arthritis: a Tunisian cross-sectional study

Sir, Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by abnormal synovial hyperplasia associated with local infiltration of various inflammatory cells leading to cartilage and bone destruction. Interleukine-17-producing T helper (Th17) cells are a recently discovered effectors T-lymphocyte subset that plays a critical role in several chronic inflammatory diseases, like RA and psoriatic arthritis (PsA) [1–4]. The objective of our study was to appreciate the role of interleukine (IL)-17, IL-23, the major Th17 driving cytokine, and CCL-20, a major Th17-attracting chemokine in the regulation of RA and PsA, by comparing concentrations in sera and in knee synovial fluid (SF) among three groups of patients, one with an active form of RA, one with active peripheral psoriatic arthritis PsA and a control group of osteoarthritis (OA) (Table 1). A case–control study was carried out, during the period of January to May 2010, in the department of Rheumatology with the Immunology laboratory of La Rabta hospital at Tunis (Tunisia). The first group of 26 patients with active form of RA (DAS 28 [ 5.1), according to the 2010 ACR/ EULAR criteria [5], was composed of 21 women and 5 men, with a mean age of 46 ± 12 years and a mean disease duration of 13.5 ± 6 months. The second group was composed of 18 patients with active peripheral PsA, fulfilling the CASPAR criteria [6], with a mean age of 35 ± 9 years and mean disease duration of 20 ± 7 months. The control group was composed of nine patients with flare-up of OA, with a mean age of 56.5 ± 12 years and a mean disease duration of 36 months ± 9. All patients were enrolled after informed consent. Paired concentrations of IL-17, IL-23, and CCL-20 in sera and in SF were determined using an enzyme-linked immuno-sorbent assay (ELISA) technique (R&B, United States). A correlation analysis was performed between parameters of RA’s activity (number of tenderness joints, number of swollen joints, number of night awakening, duration of morning stiffness, disease activity score DAS 28, modified Sharp score [7], serum and SF levels of all the mediators (IL-17, IL-23, and CCL-20). Analyses were performed using SPSS software. Non-parametric tests were used to compare the concentrations, Kruskal–Wallis and Mann–Whitney tests for the comparison of independent samples and paired Wilcoxon test for the comparison of paired samples. Correlations were calculated using the Spearman’s coefficient. A P value below 0.05 was considered as significant. The IL-17 and IL-23 levels were similar in the serum of patients with RA, PsA, and OA. This finding was also demonstrated in the joints of patients with RA, PsA, and OA. In addition, only the synovial concentrations of CCL20 were significantly higher in RA patients than the control groups (P = 0.001). However, when comparing the SF CCL-20 levels in RA versus PsA, no significant difference was found. D. Mrabet (&) S. Sellami Department of Rheumatology, La Rabta Hospital, 1007 Tunis, Tunisia e-mail: mrabetdalila@yahoo.fr

Systemic lupus erythematosus induced by interferon β1 therapy in a patient with multiple sclerosis

Drug‐induced lupus erythematosus is defined as a lupus‐like syndrome temporally related to a drug exposure. We report a 34‐year‐old woman with multiple sclerosis who developed, while being treated with interferon β‐1a, myalgia and associated with wrist synovitis. Clinical and immunologic investigations were in favor of systemic lupus erythematosus. Interferon therapy was maintained. Under corticosteroids and antipaludeen treatment, the patient did not develop any other lupic manifestations.