W. Sakly - Academia.edu (original) (raw)

Papers by W. Sakly

Research paper thumbnail of Localization of tissue transglutaminase and N (epsilon)-(gamma) -glutamyl lysine in duodenal cucosa during the development of mucosal atrophy in coeliac disease

Virchows Archiv, 2005

Expression and transamidation activity of tissue transglutaminase (tTG) may be involved in the mo... more Expression and transamidation activity of tissue transglutaminase (tTG) may be involved in the morphological modifications leading to the mucosal atrophy observed in coeliac disease (CD). We aimed to investigate the localization of tTG within the duodenal mucosa during the development of villous atrophy. The localization and level of expression of N epsilon-(gamma-glutamyl) lysine isopeptides which could reflect the transamidation activity of tTG were also analyzed. tTG and N epsilon-(gamma-glutamyl) lysine were localized using an immunohistochemical technique on duodenal biopsies obtained from 75 patients with CD and 51 subjects with normal mucosa (control group). The number of cases displaying tTG-expressing cells in the basement membrane and lamina propria was significantly higher in CD patients than in the control group. Moreover, the intensity of tTG staining in these areas was higher in CD. In contrast, the number of biopsies with tTG-expressing enterocytes was significantly lower in CD than in the control group. There was no difference in N epsilon-(gamma-glutamyl) lysine between the two populations. Tissue transglutaminase was differently expressed in the various areas of the mucosa according to the stage of atrophy, whereas the localization and the intensity of the labelling of N epsilon-(gamma-glutamyl) lysine isopeptides did not show any modification. The preferential localization in the basement membrane and lamina propria may reflect the involvement of tTG in the development of mucosal atrophy in CD.

Research paper thumbnail of Tissue transglutaminase antibodies in celiac disease, comparison of an enzyme linked immunosorbent assay and a dot blot assay

Pathologie Biologie, 2005

The purpose of our study is to determine the sensitivity, specificity and predictive values of an... more The purpose of our study is to determine the sensitivity, specificity and predictive values of an enzyme linked immunosorbent assay (ELISA) and a dot blot assay for the detection of IgA class anti-tissue transglutaminase antibodies (IgA-AtTGA) and to compare these results with those of IgA class anti-endomysium antibodies (IgA-AEA), IgA class anti-reticulin antibodies (IgA-ARA) and IgA class anti-gliadin antibodies (IgA-AGA). Serum samples from 143 patients (97 children, 46 adults) with untreated celiac disease (CD) confirmed by intestinal biopsy and 74 disease controls (64 children, 10 adults) were studied. Methods. - The anti-tissue transglutaminase antibodies were detected by dot blot assay and an ELISA using guinea pig tissue transglutaminase (gp-tTG) as antigen. The anti-endomysium antibodies were detected by an indirect immunofluorescence technique on cryostat sections of human umbilical cord. The anti-reticulin antibodies were also investigated by indirect immunofluorescence on cryostat sections of kidney, liver and stomach of rat. The anti-gliadin antibodies were determined by an ELISA. The sensitivity of an ELISA for the detection of anti-tissue transglutaminase antibodies was 86% in children and 87% in adults and the sensitivity of dot blot assay was 57% in children and 54% in adults. The specificity of an ELISA and dot blot for the detection for anti-tissue transglutaminase antibodies was, respectively, 96% and 88% lower than that of anti-endomysium antibodies (100%). The sensitivity of anti-gliadin antibodies was 97% in children and 91% in adults and their specificity was 85%. The sensitivity of anti-reticulin antibodies was 94% in children and 87% in adults. Their specificity was 100%. The sensitivity and specificity of an ELISA for the detection of anti-tissue transglutaminase antibodies were better than that of dot blot assay. However, this dot blot assay could screen four celiac patients who have not had anti-tissue transglutaminase antibodies by an ELISA. The sensitivity of anti-endomysium antibodies was better than that of anti-tissue transglutaminase antibodies, anti-reticulin antibodies and anti-gliadin antibodies but in children aged less than 2 years, the sensitivity of anti-gliadin antibodies was better than that of anti-tissue transglutaminase antibodies.

Research paper thumbnail of IgA anti-actin antibodies in celiac disease

Gastroentérologie Clinique et Biologique, 2010

Research paper thumbnail of Uveitis responding on gluten free diet in a girl with celiac disease and diabetes mellitus type 1

Gastroentérologie Clinique et Biologique, 2010

A 9-year old girl with a history of diabetes mellitus type 1, presented with visual loss of the l... more A 9-year old girl with a history of diabetes mellitus type 1, presented with visual loss of the left eye. The right eye examination was unremarkable. Slit-lamp examination revealed few small and fine keratic precipitates. We noted 2+ flare in the vitreous. There was no choroiditis, papillitis or retinal vasculitis. No aetiology was found. The patient was treated by topical and systemic corticosteroids without any improvement. Celiac disease was discovered by the presence of celiac antibodies in the work-up of joint pain and diabetes mellitus type 1. Antiendomysium antibodies and anti-transglutaminase antibodies were both positive. A small bowel biopsy confirmed celiac disease. A gluten free diet was set up and corticosteroids were tapered off. Recovery of the uveitis was obvious during gluten free diet and normalized within two months.

Research paper thumbnail of IgA anti-transglutaminase antibodies as a tool for screening atypical forms of coeliac disease in a French at-risk paediatric population

European Journal of Gastroenterology & Hepatology, 2005

The diagnosis of coeliac disease (CD) is often delayed because many children are free from the ma... more The diagnosis of coeliac disease (CD) is often delayed because many children are free from the major symptoms characteristic of this enteropathy. The aim of the present study was to determine the efficacy of antibodies directed against tissue transglutaminase (tTG Abs) for early detection of CD in a population with few symptoms of the disease, as well as in children with an autoimmune disorder. This was a prospective study in a paediatric population including 638 patients with clinical symptoms frequently associated with CD, autoimmune diseases such as type 1 diabetes mellitus (DM1), autoimmune thyroiditis or hepatitis, and Turner's syndrome. Anti-endomysium, tTG Abs and antigliadin antibodies were analysed in these patients using an indirect immunofluorescence technique and enzyme-linked immunosorbent assay techniques. Intestinal biopsies were performed for some patients with positive or negative antibodies. tTG Abs were detected in 2.6% of children with symptoms associated with CD, such as digestive signs and growth failure, and in 5.4% of children with DM1. No other autoimmune disease was positive for tTG Abs. Biopsies performed in the patients with positive tTG Abs showed mucosal atrophy confirming the diagnosis of CD in all cases. Children displaying minimal symptoms frequently associated with CD and children with DM1 should be systematically screened for tTG Abs.

Research paper thumbnail of Anticardiolipin and Anti-Beta 2 Glycoprotein I Antibodies in Infants Born to Mothers with Antiphospholipid Antibody-Positive Autoimmune Disease: A Follow-Up Study

American Journal of Perinatology, 2006

Research paper thumbnail of Phenotypic abnormalities of peripheral blood mononuclear cells in patients with Behçet’s disease and association with HLA-B51 expression

Immunological Investigations, 2014

The aim of this study was to investigate the subclasses and the immunophenotypic profile of perip... more The aim of this study was to investigate the subclasses and the immunophenotypic profile of peripheral mononuclear cells in patients with Behçet's disease (BD) and to assess associations between the expression of HLA-B51 antigen and that of other cell markers. Thirty healthy volunteer blood donors and forty patients with BD were enrolled into this study. Phenotyping was performed using two color flow cytometry. HLA-B51 typing was performed using the complement dependent microlymphocytotoxicity assay. Unlike controls, patients with BD presented a modified immunophenotypic profile of lymphocytes. Compared to those in the remission phase, patients with active BD showed an increased mean of MFI ratio of CD56 on CD16+CD56+ cells (32.47 ± 14.26 versus 23.87 ± 10.3; p = 0.032), increased absolute numbers of CD4(-)CD8(bright) and CD4(+)CD8(+) cells (657.1 ± 463.6 cells/µL versus 319.24 ± 116.4 cells/µL; p = 0.017 and 40.77 ± 36.41 cells/µL versus 10.77 ± 9.78 cells/µL; p < 0.0001, respectively) and an elevated mean of MFI ratio of CD19 on B cells (252.3 ± 56.7 versus 205.67 ± 32.3; p = 0.021). However, expression of HLA-B51 was not associated with any specific immunophenotypic profile. In conclusion, abnormal immunophenotypic profile of peripheral lymphocytes was found in patients with BD, especially in active phase, reflecting an immune dysregulation. Moreover, HLA-B51 expression was not found to be related to the expression of other cell markers.

Research paper thumbnail of Localization of tissue transglutaminase and N (epsilon)-(gamma) -glutamyl lysine in duodenal cucosa during the development of mucosal atrophy in coeliac disease

Virchows Archiv, 2005

Expression and transamidation activity of tissue transglutaminase (tTG) may be involved in the mo... more Expression and transamidation activity of tissue transglutaminase (tTG) may be involved in the morphological modifications leading to the mucosal atrophy observed in coeliac disease (CD). We aimed to investigate the localization of tTG within the duodenal mucosa during the development of villous atrophy. The localization and level of expression of N epsilon-(gamma-glutamyl) lysine isopeptides which could reflect the transamidation activity of tTG were also analyzed. tTG and N epsilon-(gamma-glutamyl) lysine were localized using an immunohistochemical technique on duodenal biopsies obtained from 75 patients with CD and 51 subjects with normal mucosa (control group). The number of cases displaying tTG-expressing cells in the basement membrane and lamina propria was significantly higher in CD patients than in the control group. Moreover, the intensity of tTG staining in these areas was higher in CD. In contrast, the number of biopsies with tTG-expressing enterocytes was significantly lower in CD than in the control group. There was no difference in N epsilon-(gamma-glutamyl) lysine between the two populations. Tissue transglutaminase was differently expressed in the various areas of the mucosa according to the stage of atrophy, whereas the localization and the intensity of the labelling of N epsilon-(gamma-glutamyl) lysine isopeptides did not show any modification. The preferential localization in the basement membrane and lamina propria may reflect the involvement of tTG in the development of mucosal atrophy in CD.

Research paper thumbnail of Tissue transglutaminase antibodies in celiac disease, comparison of an enzyme linked immunosorbent assay and a dot blot assay

Pathologie Biologie, 2005

The purpose of our study is to determine the sensitivity, specificity and predictive values of an... more The purpose of our study is to determine the sensitivity, specificity and predictive values of an enzyme linked immunosorbent assay (ELISA) and a dot blot assay for the detection of IgA class anti-tissue transglutaminase antibodies (IgA-AtTGA) and to compare these results with those of IgA class anti-endomysium antibodies (IgA-AEA), IgA class anti-reticulin antibodies (IgA-ARA) and IgA class anti-gliadin antibodies (IgA-AGA). Serum samples from 143 patients (97 children, 46 adults) with untreated celiac disease (CD) confirmed by intestinal biopsy and 74 disease controls (64 children, 10 adults) were studied. Methods. - The anti-tissue transglutaminase antibodies were detected by dot blot assay and an ELISA using guinea pig tissue transglutaminase (gp-tTG) as antigen. The anti-endomysium antibodies were detected by an indirect immunofluorescence technique on cryostat sections of human umbilical cord. The anti-reticulin antibodies were also investigated by indirect immunofluorescence on cryostat sections of kidney, liver and stomach of rat. The anti-gliadin antibodies were determined by an ELISA. The sensitivity of an ELISA for the detection of anti-tissue transglutaminase antibodies was 86% in children and 87% in adults and the sensitivity of dot blot assay was 57% in children and 54% in adults. The specificity of an ELISA and dot blot for the detection for anti-tissue transglutaminase antibodies was, respectively, 96% and 88% lower than that of anti-endomysium antibodies (100%). The sensitivity of anti-gliadin antibodies was 97% in children and 91% in adults and their specificity was 85%. The sensitivity of anti-reticulin antibodies was 94% in children and 87% in adults. Their specificity was 100%. The sensitivity and specificity of an ELISA for the detection of anti-tissue transglutaminase antibodies were better than that of dot blot assay. However, this dot blot assay could screen four celiac patients who have not had anti-tissue transglutaminase antibodies by an ELISA. The sensitivity of anti-endomysium antibodies was better than that of anti-tissue transglutaminase antibodies, anti-reticulin antibodies and anti-gliadin antibodies but in children aged less than 2 years, the sensitivity of anti-gliadin antibodies was better than that of anti-tissue transglutaminase antibodies.

Research paper thumbnail of IgA anti-actin antibodies in celiac disease

Gastroentérologie Clinique et Biologique, 2010

Research paper thumbnail of Uveitis responding on gluten free diet in a girl with celiac disease and diabetes mellitus type 1

Gastroentérologie Clinique et Biologique, 2010

A 9-year old girl with a history of diabetes mellitus type 1, presented with visual loss of the l... more A 9-year old girl with a history of diabetes mellitus type 1, presented with visual loss of the left eye. The right eye examination was unremarkable. Slit-lamp examination revealed few small and fine keratic precipitates. We noted 2+ flare in the vitreous. There was no choroiditis, papillitis or retinal vasculitis. No aetiology was found. The patient was treated by topical and systemic corticosteroids without any improvement. Celiac disease was discovered by the presence of celiac antibodies in the work-up of joint pain and diabetes mellitus type 1. Antiendomysium antibodies and anti-transglutaminase antibodies were both positive. A small bowel biopsy confirmed celiac disease. A gluten free diet was set up and corticosteroids were tapered off. Recovery of the uveitis was obvious during gluten free diet and normalized within two months.

Research paper thumbnail of IgA anti-transglutaminase antibodies as a tool for screening atypical forms of coeliac disease in a French at-risk paediatric population

European Journal of Gastroenterology & Hepatology, 2005

The diagnosis of coeliac disease (CD) is often delayed because many children are free from the ma... more The diagnosis of coeliac disease (CD) is often delayed because many children are free from the major symptoms characteristic of this enteropathy. The aim of the present study was to determine the efficacy of antibodies directed against tissue transglutaminase (tTG Abs) for early detection of CD in a population with few symptoms of the disease, as well as in children with an autoimmune disorder. This was a prospective study in a paediatric population including 638 patients with clinical symptoms frequently associated with CD, autoimmune diseases such as type 1 diabetes mellitus (DM1), autoimmune thyroiditis or hepatitis, and Turner's syndrome. Anti-endomysium, tTG Abs and antigliadin antibodies were analysed in these patients using an indirect immunofluorescence technique and enzyme-linked immunosorbent assay techniques. Intestinal biopsies were performed for some patients with positive or negative antibodies. tTG Abs were detected in 2.6% of children with symptoms associated with CD, such as digestive signs and growth failure, and in 5.4% of children with DM1. No other autoimmune disease was positive for tTG Abs. Biopsies performed in the patients with positive tTG Abs showed mucosal atrophy confirming the diagnosis of CD in all cases. Children displaying minimal symptoms frequently associated with CD and children with DM1 should be systematically screened for tTG Abs.

Research paper thumbnail of Anticardiolipin and Anti-Beta 2 Glycoprotein I Antibodies in Infants Born to Mothers with Antiphospholipid Antibody-Positive Autoimmune Disease: A Follow-Up Study

American Journal of Perinatology, 2006

Research paper thumbnail of Phenotypic abnormalities of peripheral blood mononuclear cells in patients with Behçet’s disease and association with HLA-B51 expression

Immunological Investigations, 2014

The aim of this study was to investigate the subclasses and the immunophenotypic profile of perip... more The aim of this study was to investigate the subclasses and the immunophenotypic profile of peripheral mononuclear cells in patients with Behçet's disease (BD) and to assess associations between the expression of HLA-B51 antigen and that of other cell markers. Thirty healthy volunteer blood donors and forty patients with BD were enrolled into this study. Phenotyping was performed using two color flow cytometry. HLA-B51 typing was performed using the complement dependent microlymphocytotoxicity assay. Unlike controls, patients with BD presented a modified immunophenotypic profile of lymphocytes. Compared to those in the remission phase, patients with active BD showed an increased mean of MFI ratio of CD56 on CD16+CD56+ cells (32.47 ± 14.26 versus 23.87 ± 10.3; p = 0.032), increased absolute numbers of CD4(-)CD8(bright) and CD4(+)CD8(+) cells (657.1 ± 463.6 cells/µL versus 319.24 ± 116.4 cells/µL; p = 0.017 and 40.77 ± 36.41 cells/µL versus 10.77 ± 9.78 cells/µL; p < 0.0001, respectively) and an elevated mean of MFI ratio of CD19 on B cells (252.3 ± 56.7 versus 205.67 ± 32.3; p = 0.021). However, expression of HLA-B51 was not associated with any specific immunophenotypic profile. In conclusion, abnormal immunophenotypic profile of peripheral lymphocytes was found in patients with BD, especially in active phase, reflecting an immune dysregulation. Moreover, HLA-B51 expression was not found to be related to the expression of other cell markers.