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D Anglicheau,
A Loupy,
C Lefaucheur,
F Pessione,
I Létourneau,
I Côté,
K Gaha,
L-H Noël, N Patey,
D Droz,
F Martinez,
J Zuber,
D Glotz,
E Thervet,
C Legendre
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ABSTRACT: The predictive value of pre-implantation biopsies versus clinical scores has not been studied extensively in marginal donors. Pre-implantation biopsies were performed in 313 kidneys from donors that were > or = 50 years of age (training set, n = 191; validation set, n = 122). The value of the donor clinical parameters and histological results in predicting 1-year estimated glomerular filtration rate (eGFR) <25 mL/min/1.73 m(2) was retrospectively evaluated. In multivariate analysis, the only clinical parameters associated with low eGFR were donor hypertension and a serum creatinine level > or =150 micromol/L before organ recovery. Clinical scores (Nyberg and Pessione) were not significantly associated with graft function. Regarding histological parameters, univariate analysis showed that glomerulosclerosis (GS) (p = 0.02), arteriolar hyalinosis (p = 0.03) and the Pirani (p = 0.02) and chronic allograft damage index (CADI) (p = 0.04) histological scores were associated with low eGFR. The highest performance in predicting low eGFR was achieved using a composite score that included donor serum creatinine (> or =150 micromol/L or <150 micromol/L), donor hypertension and GS (> or =10% or <10%). The validation set confirmed the critical importance of taking into account biopsy and clinical parameters during marginal donor evaluation. In conclusion, clinical scores are weak predictors of graft outcomes with marginal donors. Instead, a simple and convenient composite score strongly predicts graft function and survival and may facilitate optimal allocation of marginal donors.
American Journal of Transplantation 09/2008; 8(11):2325-34. · 6.39 Impact Factor
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D Anglicheau,
A Loupy,
C Suberbielle,
J Zuber, N Patey,
L-H Noël,
R Cavalcanti,
M Le Quintrec,
F Audat,
A Méjean,
F Martinez,
M-F Mamzer-Bruneel,
E Thervet,
C Legendre
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ABSTRACT: The effects of posttransplant prophylactic intravenous immunoglobulin (IVIg) were investigated in renal transplant recipients at high immunological risk. Thirty-eight deceased-donor kidney transplant recipients with previous positive complement-dependent cytotoxicity crossmatch (n=30), and/or donor-specific anti-HLA antibodies (n=14) were recruited. IVIg (2 g/kg) was administrated on days 0, 21, 42 and 63 with quadruple immunosuppression. Biopsy-proven acute cellular and humoral rejection rates at month 12 were 18% and 10%, respectively. Glomerulitis was observed in 31% and 60% of patients at months 3 and 12, respectively, while allograft glomerulopathy rose from 3% at month 3 to 28% at 12 months. Interstitial fibrosis/tubular atrophy increased from 18% at day 0 to 51% and 72% at months 3 and 12 (p<0.0001). GFR was 50 +/- 17 mL/min/1.73 m(2) and 48 +/- 17 mL/min/1.73 m(2) at 3 and 12 months. PRA decreased significantly after IVIg (class I: from 18 +/- 27% to 5 +/- 12%, p<0.01; class II: from 25 +/- 30% to 7 +/- 16%, p<0.001). Patient and graft survival were 97% and 95%, respectively and no graft was lost due to rejection (mean follow-up 25 months). In conclusion, prophylactic IVIg in high-immunological risk patients is associated with good one-year outcomes, with adequate GFR and a profound decrease in PRA level, but a significant increase in allograft nephropathy.
American Journal of Transplantation 05/2007; 7(5):1185-92. · 6.39 Impact Factor
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O. Goulet,
F. Ruemmele,
C. Talbotec,
N. Youssef,
A. Morali,
V. Colomb,
N. Cerf-Bensussan, N. Patey,
F. Ferretti,
A. Barabino,
P. Rogerro,
J. P. Chouraqui,
J. Schmitz,
N. Brousse
Journal of Pediatric Gastroenterology and Nutrition 05/2004; 39:S393. · 2.30 Impact Factor
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ABSTRACT: Lymphoproliferative disorders (LPDs) are a severe complication in primary immunodeficiency and post-transplant patients. In primary immunodeficiency patients, LPDs are not well-known and, thus, we tried to evaluate their distinctive features and to determine prognostic factors predictive of clinical outcome by comparison with LPDs in post-transplant children.
Clinical records and histopathology of 18 LPDs occurring in primary immunodeficieny children were compared with those of 10 LPDs in post-transplant children, together with results of in-situ hybridization for the detection of Epstein-Barr virus (EBV)-RNA and molecular biological techniques. LPDs were frequently extranodal, EBV-associated, and were more commonly pleomorphic in primary immunodeficiency than in post-transplant patients. A low T-cell count and abnormal T-cell function indicated bad prognosis in both groups. Polymorphic LPDs (PLPDs) were most frequent (n = 19), whereas lymphomas were rare (n = 7), and pseudo-tumoral lymphoid hyperplasias (n = 2) were observed only in primary immunodeficiency. Comparative p53/bcl-2 staining revealed a p53 overexpression in lymphomas compared with PLPDs; CD20/CD79a showed a similar staining in lymphomas, whereas PLPD expressed mainly CD20. TCR and IgH rearrangements did not help in distinguishing PLPDs from lymphomas, but detection of IgH clonality by Southern blot indicated poor prognosis, whereas oligoclonality by Southern blot regardless of PCR clonality and especially a polyclonal profile by Southern blot and PCR indicated a relatively good prognosis.
This study documents the pleomorphism of LPDs in primary immunodeficiency compared to post-transplant children, even if some LPDs are similar in both groups (PLPDs). No criteria are useful enough to ascertain the diagnosis of malignancy in this series. Some molecular biological criteria help to predict the clinical outcome which, nevertheless, seems to depend more on the degree of immunosuppression and on T-lymphocyte presence and function.
Histopathology 03/2001; 38(2):146-59. · 3.08 Impact Factor
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ABSTRACT: Adult refractory sprue is a poorly defined disorder. We did a multicentre national study of patients with refractory sprue to characterise their clinical and pathological profile and outcome, and to assess the frequency and prognostic significance of phenotypic and molecular abnormalities in the intraepithelial T-cell population.
Patients with severe symptomatic villous atrophy mimicking coeliac disease but refractory to a strict gluten-free diet, and with no initial evidence of overt lymphoma, were diagnosed at gastrointestinal referral centres between 1974 and 1998. Fixed and/or frozen duodenojejunal biopsy samples were reanalysed and immunostained with CD3 and CD8 monoclonal antibodies to find out the phenotype of intraepithelial lymphocytes (IEL). TCRgamma gene rearrangements were assessed on frozen biopsy samples by multiplex fluorescent PCR.
There were 21 patients with refractory sprue and 20 controls with coeliacs disease. 16 (84%) of 19 assessed patients had an aberrant intraepithelial lymphoid intestinal population expressing intracytoplasmic CD3 but not surface CD8. Clonal intestinal TCRgamma gene rearrangements were found in 13 (76%) of 17 patients assessed; four (out of 12 assessed) had clonal dissemination to the blood. The 16 patients with an aberrant phenotype all had uncontrolled malabsorption; three subsequently developed overt T-cell lymphoma, and eight died. The three (16%) patients without aberrant clonal IEL made a complete clinical and histological recovery with steroid therapy plus a gluten-free diet.
An immunophenotypically aberrant clonal intraepithelial T-cell population (similar to that of most cases of enteropathy-associated T-cell lymphoma) can be found in up to 75% of patients with refractory coeliac sprue; its identification by simple diagnostic techniques represents a marker of poor outcome (including occurrence of overt T-cell lymphoma). We suggest that refractory sprue associated with an aberrant clonal IEL may be the missing link between coeliac disease and T-cell lymphoma and may be classified as cryptic enteropathy-associated T-cell lymphoma.
The Lancet 08/2000; 356(9225):203-8. · 38.28 Impact Factor
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ABSTRACT: An increase in the number of intraepithelial lymphocytes (IEL) in the rectal epithelium of patients with active celiac disease has been described. No data are available about how they vary during a gluten-free diet. The aim of the study was to assess the effect of a gluten-free diet on T-cell activation in the rectal mucosa of adult patients with celiac disease.
Frozen duodenal and rectal biopsies were available in four celiac patients (one male, three female, mean age 39 yr) both before and after 7 to 24 months on a gluten-free diet. Biopsy samples were stained using monoclonal antibodies directed against CD3, betaF1, TcRdelta1, CD25, and HLADR. Numbers of IEL were estimated by counting the peroxidase-stained cells per 100 epithelial cells. Four patients without histological abnormalities were used as control subjects.
In the four patients with active celiac disease but in none of the controls, CD25 was expressed by both duodenal and rectal lamina propria cells and HLADR was expressed by duodenal (4/4) and rectal (2/4) epithelial cells. In addition, two patients with active celiac disease had features of lymphocytic colitis, i.e., >20 IEL per 100 epithelial cells. After a gluten-free diet, the mean number of rectal CD3+ betaF1+ IEL decreased (9% vs 21%) and the expression of CD25 and HLADR was no longer present. These changes mirrored those found in the small intestinal biopsies.
These results suggest that in celiac disease, gluten-driven T-cell activation is not restricted to the proximal part of the intestine but is present on the whole intestinal length. Assessment of the effectiveness of a gluten-free diet through rectal biopsies warrants investigation, as it could lessen discomfort for patients and prove more cost-effective.
The American Journal of Gastroenterology 09/1998; 93(9):1527-30. · 7.28 Impact Factor
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ABSTRACT: En cas de sprue réfractaire, l’entéroscopie permet dans plus de 50% des cas, le diagnostic de jéjunite ulcéreuse. En cas de
maladie cœliaque sensible au régime sans gluten, l’entéroscopie n’a pas d’intérêt diagnostique ou thérapeutique car l’atrophie
villositaire la plus sévère est toujours présente au niveau du duodénum. Chez les malades avec une malabsorption inexpliquée,
la rentabilité diagnostique de l’entéroscopie est de 18%.
Acta Endoscopica 05/1998; 28(5):630-630. · 0.09 Impact Factor
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C Cellier, N Patey,
L Mauvieux,
B Jabri,
E Delabesse,
J P Cervoni,
M L Burtin,
D Guy-Grand,
Y Bouhnik,
R Modigliani,
J P Barbier,
E Macintyre,
N Brousse,
N Cerf-Bensussan
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ABSTRACT: The etiology of refractory sprue is unclear. To gain insight into its pathogenesis, the phenotype and T-cell receptor (TCR) gene rearrangement status of intestinal lymphocytes were analyzed in a group of patients with clinical or biological features of celiac disease but either initially or subsequently refractory to a gluten-free diet.
Intestinal biopsy specimens were obtained from 26 adults: 6 patients with refractory sprue, 7 patients with active celiac disease, and 13 normal controls. The phenotype of intestinal lymphocytes was studied by immunohistochemistry and, in 3 patients with refractory sprue, by cytometry of lymphocytes purified from intestinal biopsy specimens. TCR rearrangements were assessed by studying TCRgammaV-J junctional regions from DNA extracted from intestinal biopsy specimens and purified intestinal lymphocytes.
In the 6 patients with refractory sprue, but not in normal controls or patients with active celiac disease, the intestinal epithelium was massively infiltrated by small lymphocytes that lacked CD8, CD4, and TCR, contained intracytoplasmic but not surface CD3epsilon chains, and exhibited restricted TCRgamma gene rearrangements.
Refractory sprue is associated with an abnormal subset of intraepithelial lymphocytes containing CD3epsilon and restricted rearrangements of the TCRgamma chain but lacking surface expression of T-cell receptors.
Gastroenterology 04/1998; 114(3):471-81. · 11.68 Impact Factor
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Archives De Pediatrie - ARCHIVES PEDIATRIE. 01/1998; 5(2):233-233.
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ABSTRACT: Little is known of the in-situ expression of adhesion molecules in ulcerative colitis (UC) according to disease activity. In the present study we investigate the vascular expression of endothelial leucocyte adhesion molecule 1 (ELAM-1/E-selectin), vascular cell adhesion molecule (VCAM-1) and intercellular adhesion molecules (ICAM-1 and ICAM-3) on the rectal mucosa of patients with UC in order to identify links between in-situ expression of these adhesion molecules and clinical, endoscopic and histological parameters.
At inclusion, 16 untreated patients with UC at different stages of disease activity were assessed clinically and endoscopically and underwent rectal biopsy. Ten patients had similar assessments during follow-up. Quantitative histological and immunohistochemical scores were established with anti-E-selectin, VCAM-1, ICAM-1, ICAM-3 and HLA-DR monoclonal antibodies on frozen biopsy specimens.
(1) At inclusion, E-selectin in-situ expression correlated with clinical activity (r = 0.7, P = 0.05), endoscopic severity (r = 0.74, P = 0.04), the histological score (r = 0.57, P = 0.02) and in-situ expression of HLA-DR on epithelial cells (r = 0.74, P = 0.01). (2) After remission, there was a significant decrease in ELAM-1 in-situ expression (P = 0.04). (3) In patients with clinical, endoscopic and histological remission the level of residual E-selectin expression appeared to be predictive of clinical relapse. (4) Vascular expression of VCAM-1 and ICAM-1 did not correlate with clinical, endoscopic or histological parameters, or with changes in disease activity. (5) ICAM-3 was never detected on endothelial cells of the colonic mucosa of controls or patients with UC.
In ulcerative colitis, E-selectin, but not VCAM-1, ICAM-1 or ICAM-3, appears to play a central role in leucocyte migration into the colonic mucosa. Elevated vascular expression of E-selectin after remission may be involved in clinical recurrence.
European Journal of Gastroenterology & Hepatology 01/1998; 9(12):1197-203. · 1.76 Impact Factor
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ABSTRACT: Intestinal epithelial dysplasia, or tufting enteropathy, is a newly described clinicopathologic entity with refractory diarrhea in infants. Histological abnormalities include villous atrophy, disorganization of the surface epithelium, and basement membrane abnormalities. The aim of this study was to examine defects in intestinal epithelial cell adhesion, differentiation, or proliferation in the pathogenesis of epithelial dysplasia.
Histological, immunohistochemical, and ultrastructural characteristics of epithelial dysplasia in a group of 6 children were compared with those groups with normal small bowel and other villous atrophy (celiac sprue and microvillous inclusion disease). Distribution of adhesion molecules, markers of cell polarization and proliferation, and the phenotype of intraepithelial lymphocytes were determined.
Alterations suggestive of abnormal cell-cell and cell-matrix interactions were present in patients with epithelial dysplasia. They included abnormal distribution of alpha 2 beta 1 integrin along the crypt-villus axis, increased immunohistochemical expression of desmoglein, and ultrastructural changes of desmosomes increased in length and number. No evidence for abnormalities in epithelial cell polarization, proliferation, or T-cell activation was found.
This study strongly suggests a role played by alterations of cell-cell and cell-matrix interactions in the pathogenesis of epithelial dysplasia.
Gastroenterology 09/1997; 113(3):833-43. · 11.68 Impact Factor
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ABSTRACT: We describe two children with a severe combined immune deficiency (SCID) with B cells. Following a T-cell-depleted haploidentical bone marrow transplantation (BMT), they both developed a chronic graft-versus-host disease (GVHD) of the skin and a severe persisting hyperbilirubinaemia and elevated liver enzymes. The diagnosis of a vanishing bile duct syndrome was confirmed by liver biopsies. Because corticosteroids and cyclosporin A induced only a partial response, ursodeoxycholic acid (UDCA) was added to their treatment schedule. Serum bilirubin and liver enzymes returned to normal within months. A control liver biopsy showed normal and proliferating bile ducts without cholestatic damage. We conclude that UDCA was well tolerated and may be of value as an additional treatment for hepatic GVHD in SCID.
British Journal of Haematology 04/1997; 96(4):776-80. · 4.94 Impact Factor
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Gastroentérologie Clinique et Biologique 02/1997; 21(11):832-42. · 0.80 Impact Factor
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La Revue de Médecine Interne 02/1997; 18(5):418-20. · 0.61 Impact Factor
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J F Emile, N Patey,
F Altare,
S Lamhamedi,
E Jouanguy,
F Boman,
J Quillard,
M Lecomte-Houcke,
O Verola,
J F Mousnier,
F Dijoud,
S Blanche,
A Fischer,
N Brousse,
J L Casanova
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ABSTRACT: Bacillus Calmette Guérin (BCG) is an attenuated strain of Mycobacterium bovis that is currently used as a live vaccine for human tuberculosis. Disseminated BCG infection may rarely occur following vaccination of children. In half of the cases, regarded as idiopathic, no well-defined immunodeficiency condition can account for the infection. However, the high rates of parental consanguinity and familial forms and the associated opportunistic infections with Salmonella suggest that these idiopathic BCG infections result from one or several new type(s) of inherited immune disorder(s). As an approach to the description and understanding of this newly described condition, the associated lesions were examined. Samples from 14 patients collected from a French national retrospective study were analysed. Pathological data from 22 cases reported in the world literature were also reviewed. Two types of granuloma were found. The first type (type I, tuberculoid) consisted of well-circumscribed and well-differentiated granulomas, with epithelioid and multinucleated giant cells containing very few acid-fast rods, surrounded by lymphocytes and fibrosis and occasionally with central caseous necrosis. The second type (type II, lepromatous-like) consisted of ill-defined and poorly differentiated granulomas, with few if any giant cells and lymphocytes but widespread macrophages loaded with acid-fast bacilli. Most children displayed a single type of granuloma. One half displayed type 1 lesions and the other half displayed type II lesions. There was a strong correlation between the type of granuloma and the clinical outcome. Tuberculoid lesions were associated with survival, whilst lepromatous-like lesions correlated with death. Correlation of granuloma structure with clinical outcome defines two types of idiopathic disseminated BCG infection. The phenotypic heterogeneity of the course of BCG infection reflects distinct pathogenic mechanisms and probably results from a genotypic heterogeneity of the underlying inherited immune disorder.
The Journal of Pathology 02/1997; 181(1):25-30. · 6.32 Impact Factor
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ABSTRACT: The expression of the intercellular adhesion molecule-1 (ICAM-1) and its ligand lymphocyte function associated antigen-1 (LFA-1 or alpha L), the vascular cell adhesion molecule-1 (VCAM-1), endothelial leukocyte adhesion molecule-1 (ELAM-1), and the cellular receptors for extracellular matrix, alpha 1, alpha 2, alpha 3, alpha 5, alpha 6, alpha V, beta 1, and beta 3 integrin subunits, was studied in 28 patients with crescentic glomerulonephritis (GN) related to several mechanisms: four patients with anti-glomerular basement membrane antibodies or anti-GBM disease; 16 with immune complex mediated GN; and eight with pauci-immune GN, associated with vasculitis in four cases. A three-step immunoperoxidase technique was used on sections obtained from frozen renal biopsies. At the initial stage of evolution of the lesions, all the cells of the crescents expressed the beta 1, beta 3, alpha 1, alpha 3, and alpha V subunits of integrins, ICAM-1, and VCAM-1, and some cells expressed the alpha 2, alpha 5, alpha 6, and alpha L subunits of integrins along the plasma membrane. At a later stage, when the crescents were fibrocellular, alpha 3 and alpha 1 subunit expression was polarized, localized mainly in front of the extracellular matrix. In fibrotic crescents, the alpha 2, alpha 5, alpha 6, and alpha L chains were no longer detected, and VCAM-1 and ICAM-1 expression was decreased. VCAM-1 and ELAM-1 appeared on endothelial cells of peritubular capillaries in relation to the appearance of infiltrating inflammatory cells. The results of this study show that several adhesion molecules were expressed on cells forming crescents and were modified during crescent evolution; that these molecules were up-regulated on endothelial cells in relation to the severity of the inflammatory response; and that whatever the mechanism of the glomerulonephritis, adhesion molecule expression was identical. It can be postulated that adhesion molecules play a role in crescentic glomerulonephritis. Better knowledge of these molecules in human glomerulonephritis may open the way to a new therapeutic approach.
The Journal of Pathology 09/1996; 179(4):414-20. · 6.32 Impact Factor
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Journal of Pediatric Gastroenterology and Nutrition 04/1996; 22(4):439. · 2.30 Impact Factor
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ABSTRACT: Intercellular adhesion molecule-3 (ICAM-3) was identified as the third counter-receptor for lymphocyte function-associated antigen-1. ICAM-3 is absent on endothelial cells in normal tissues but found on endothelial cells in lymphomas. Here, we examined ICAM-3 expression on vascular endothelial cells in lymphomas, nonlymphoid malignancies, benign tumors, and inflammatory diseases. We compared the expression of ICAM-3 on endothelial cells with the severity of inflammatory infiltrates and with the presence of E-selectin and VCAM-1. We found that ICAM-3 expression on endothelial cells was high on both benign and malignant tumors whereas it was low in inflammatory diseases. In contrast to E-selectin, ICAM-3 expression on endothelial cells was not correlated to the severity of inflammatory infiltrates. In hemangiomas, we showed by Northern blot analysis and immunocytochemistry that ICAM-3 expression was induced and that it was localized in immature areas that sustain the early stages of angiogenesis. Therefore, expression of ICAM-3 on blood vessels does not seem to play a role in the recruitment of leukocytes during inflammation but rather is correlated with angiogenesis and tumor development.
American Journal Of Pathology 03/1996; 148(2):465-72. · 4.89 Impact Factor
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ABSTRACT: Seven children with short bowel syndrome underwent small bowel allografting. Episodes of early rejection were observed in five patients who received a graft from paediatric or adult donors but not in two patients who received a neonatal graft. This study aimed, firstly, to define immunohistochemical parameters accompanying rejection and, secondly, to compare immunohistochemical parameters in neonatal grafts with those in grafts from older donors. An immunohistochemical analysis was performed on 85 intestinal biopsy specimens taken for monitoring the transplant. Acute histological rejection was associated with pericryptic infiltrates of CD3+TcR alpha beta + T cells containing clusters of CD8+ cells, numerous CD25+ cells, and increased numbers of CD68+ macrophages. These changes were associated with the appearance of major histocompatibility (MHC) class II antigens on crypt enterocytes and with an appreciable increase in the expression of E-selectin on mucosal endothelial cells. Immunohistochemistry was useful in predicting rejection by showing the appearance of pericryptic CD25+ T cells 48 hours before the first histological lesions of crypt necrosis. Comparison of neonatal grafts with grafts from older donors did not show any significant difference in the density of CD68+ macrophages or in the endothelial expression of intercellular adhesion molecule-1, vascular cell adhesion molecule-1, or E-selectin. In contrast to grafts from older donors, however, neonatal grafts did not express MHC class II antigens on epithelial cells and contained very low numbers of intraepithelial lymphocytes. These data indicate, firstly, that immunohistochemistry is useful for monitoring intestinal transplants and, secondly, that the better clinical tolerance of neonatal allografts may be related to the lower immunogenicity of the neonatal epithelium.
Gut 01/1996; 37(6):783-90. · 10.11 Impact Factor
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ABSTRACT: A 69 year old woman developed chronic diarrhoea while being treated with ranitidine. Sigmoidoscopy was performed after six weeks and showed typical histological features of lymphocytic colitis. Ranitidine was withdrawn and the diarrhoea resolved. Eight months later, a 72 hour oral rechallenge period of ranitidine, was performed immediately preceded (period 1) and followed (period 2) by sigmoidoscopy and biopsy. Diarrhoea recurred during the rechallenge period and resolved again within one day after drug withdrawal. The mean (SEM) intraepithelial lymphocyte count was not significantly different between periods 1 and 2 (11.9 (0.6) and 13.1 (0.4) per 100, respectively). An immunopathological study of 30 serial sections of biopsy specimens was performed for both periods 1 and 2. The expression of HLA-DR by the rectal epithelium was mild or absent in all sections from period 1, and was considerable in 25 of 30 sections from period 2 (p < 10(-9)). It is suggested that the oral intake of ranitidine was responsible for the diarrhoea and induced the immunopathological signs of activation of the rectal mucosal immune system during the rechallenge period.
Gut 12/1995; 37(5):708-11. · 10.11 Impact Factor
