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Georgia Malamut,
Olivia Chandesris,
Virginie Verkarre,
Bertrand Meresse,
Céline Callens,
Elizabeth Macintyre,
Yoram Bouhnik,
Jean-Marc Gornet,
Matthieu Allez,
Raymond Jian,
Anne Berger,
Gilles Châtellier,
Nicole Brousse,
Olivier Hermine,
Nadine Cerf-Bensussan,
Christophe Cellier
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ABSTRACT: INTRODUCTION: Prognosis of enteropathy-associated T cell lymphoma is poor but predictors of survival remain ill-defined. How clinical presentation, pathological features and therapies influence outcome was evaluated in 37 thoroughly characterized patients with celiac disease and T-cell lymphoma. PATIENTS AND METHODS: Medical files were studied retrospectively. Lymphoma and intestinal mucosa were analysed by histopathology, multiplex PCR and intestinal intraepithelial lymphocytes phenotyping. Survival and prognostic factors were analysed using Kaplan-Meier curves with Logrank test and Cox Model. RESULTS: Lymphoma complicated non clonal enteropathy, celiac disease (n=15) and type I refractory celiac disease (n=2) in 17 patients and clonal type II refractory celiac disease in 20 patients. Twenty-five patients underwent surgery with resection of the main tumour mass in 22 cases. In univariate analysis, non clonal celiac disease, serum albumin level>21.6g/L at diagnosis, chemotherapy and surgical resection predicted good survival (p=0.0007, p<0.0001, p<0.0001, p<0.0001, respectively). In multivariate analysis, serum albumin level>21.6g/L, chemotherapy and reductive surgery were all significantly associated with increased survival (p<0.002, p<0.03, p<0.03, respectively). CONCLUSIONS: Our study underlines the prognostic value of celiac disease type in patients with T-cell lymphoma, and suggests that a combination of nutritional, chemotherapy and reductive surgery may improve survival.
Digestive and Liver Disease 01/2013; · 3.05 Impact Factor
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ABSTRACT: A small subset of patients with celiac disease become refractory to a gluten-free diet, with persistent or recurrent symptoms of malabsorption and intestinal villous atrophy. This condition, defined as refractory celiac disease (RCD), is diagnosed after other small bowel diseases with villous atrophy are excluded. RCD is subdivided into 2 subgroups: type I RCD and type II RCD (RCDII). This latter condition is considered a low-grade intraepithelial lymphoma and has a poor prognosis. This article reviews the clinical and pathologic features of RCD and recent pathogenic findings in RCDII, offering a model to study how inflammation can drive T-cell lymphomagenesis.
Gastrointestinal endoscopy clinics of North America 10/2012; 22(4):759-72.
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Maximilien Barret, Georgia Malamut,
Gabriel Rahmi,
Elia Samaha,
Joël Edery,
Virginie Verkarre,
Elizabeth Macintyre,
Emilie Lenain,
Gilles Chatellier,
Nadine Cerf-Bensussan,
Christophe Cellier
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ABSTRACT: Capsule endoscopy (CE) allows for the assessment of the small bowel in numerous intestinal diseases, including celiac disease (CD). The main advantage of CE is the complete visualization of the intestinal mucosal surface. The objective of this study was to investigate whether CE can predict the severity of CD and detect complications.
We retrospectively studied the medical files of 9 patients with symptomatic CD, 11 patients with refractory celiac disease type I (RCDI) and 18 patients with refractory celiac disease type II (RCDII), and 45 patients without CD who were investigated both CE and upper endoscopy or enteroscopy. The type of CD was diagnosed on the basis of a centralized histological review, flow cytometry analysis of intraepithelial lymphocytes, and the analysis of T-cell receptor rearrangement by multiplex polymerase chain reaction.
A total of 47 CEs (10, 11, and 26 CEs in the symptomatic CD, RCDI, and RCDII groups, respectively) from the 38 celiac patients and 47 CEs from the 45 nonceliac patients were retrospectively reviewed. Villous atrophy, numerous, or distally located ulcers were more frequent in celiac patients than in controls. Among celiac patients, CE was of acceptable quality in 96% of cases and was complete in 62% of cases. The concordance of CE with histology for villous atrophy was better than that of optic endoscopy (κ coefficient =0.45 vs. 0.24, P<0.001). Extensive mucosal damage on CE was associated with low serum albumin (P=0.003) and the RCDII form (P=0.02). Three cases of overt lymphoma were detected by CE during the follow-up.
CE findings have a satisfactory concordance with histology and nutritional status in patients with symptomatic or refractory CD. Moreover, CE may predict the type of RCD and allows for the early detection of overt lymphoma.
The American Journal of Gastroenterology 09/2012; 107(10):1546-53. · 7.28 Impact Factor
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Georgia Malamut,
Bertrand Meresse,
Virginie Verkarre,
Sophie Kaltenbach,
Nicolas Montcuquet,
Jean-Paul Duong Van Huyen,
Céline Callens,
Julien Lenglet,
Gabriel Rahmi,
Elia Samaha,
Brigitte Ranque,
Elizabeth Macintyre,
Isabelle Radford-Weiss,
Olivier Hermine,
Nadine Cerf-Bensussan,
Christophe Cellier
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ABSTRACT: Large granular lymphocyte leukemia (LGL) is characterized by clonal expansion of CD3+ T cells or CD3(-) natural killer cells and frequently is associated with autoimmune diseases. We describe 2 patients with celiac disease who no longer responded to gluten-free diets after they developed T-cell LGL, with intestinal localization of malignant lymphocytes. Flow cytometry phenotyping of isolated intestinal intraepithelial and lamina propria cells eliminated type II refractory celiac disease, identifying large-sized CD8(+)CD57(+) T cells. Treatment with a combination of cyclosporine and methotrexate restored the patients' sensitivity to gluten-free diets. LGL therefore might be a cause of refractory celiac disease that is sensitive to immunosuppressive therapy.
Gastroenterology 08/2012; · 11.68 Impact Factor
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ABSTRACT: Obscure gastrointestinal bleeding has long been a diagnostic challenge because of the relative inaccessibility of small bowel to standard endoscopic evaluation. Intraoperative enteroscopy indications have been reduced by the development of deep enteroscopy techniques and video capsule endoscopy. In light of the current advances, this review aimed at evaluating the intraoperative enteroscopy technical aspects, study results and an ongoing role for intraoperative enteroscopy in obscure gastrointestinal bleeding management. Intraoperative enteroscopy allows complete small bowel exploration in 57-100% of cases. A bleeding source can be identified in 80% of cases. Main causes are vascular lesions (61%) and benign ulcers (19%). When a lesion is found, intraoperative enteroscopy allows successful and recurrence-free management of gastrointestinal bleeding in 76% of cases. The reported mortality is 5% and morbidity is 17%. The recurrence of bleeding is observed in 13-52% of cases. With the recent development of deep enteroscopy techniques, intraoperative enteroscopy remains indicated when small bowel lesions (i) have been identified by a preoperative work-up, (ii) cannot be definitively managed by angiographic embolization, endoscopic treatment or when surgery is required and (iii) cannot be localized by external examination during surgical explorations. Surgeons and endoscopists must exercise caution with intraoperative enteroscopy to avoid the use of a low yield, highly morbid procedure.
Digestive and Liver Disease 08/2012; · 3.05 Impact Factor
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ABSTRACT: Refractory celiac disease is defined by the persistence of symptoms of malnutrition and intestinal villous atrophy for more than 6-12 months despite strict gluten-free diet in celiac patients. Diagnosis of this rare condition is made after excluding other causes of chronic small intestinal inflammation and villous atrophy and inadvertent intake of gluten. Over the past 15 years, multidisciplinary approaches have been developed to assess the mechanism of resistance to the diet, and two distinct entities have been delineated. Type II refractory celiac disease (RCD) can be defined as a low-grade intraepithelial lymphoma. RCD II is characterised by a massive accumulation of abnormal IEL that display an aberrant hybrid NK/T cell phenotype, contain clonal T cell rearrangement(s) and can mediate a cytolytic attack of the gut epithelium. This condition has a severe prognosis, largely due to the frequent transformation of RCDII IEL into overt aggressive enteropathy-type-associated T cell lymphoma. In contrast, in type I RCD, intestinal lymphocytes have a normal phenotype, and this generally milder condition remains often difficult to differentiate from uncomplicated CD except for the resistance to gluten-free diet (GFD). Several mechanisms may underlie resistance to gluten. Herein, we review the distinctive characteristics of RCD I and RCD II, the mechanisms underlying the onset of resistance to GFD, the risk of developing high grade lymphoma and possible clues to improve their treatment.
Seminars in Immunopathology 07/2012; 34(4):601-13. · 6.27 Impact Factor
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ABSTRACT: Celiac disease (CD) is a chronic enteropathy induced by dietary gluten in genetically predisposed people. The keystone of CD pathogenesis is an adaptive immune response orchestrated by the interplay between gluten and MHC class II HLA-DQ2 and DQ8 molecules. Yet, other factors that impair immunoregulatory mechanisms and/or activate the large population of intestinal intraepithelial lymphocytes (IEL) are indispensable for driving tissue damage. Herein, we summarize our current understanding of the mechanisms and consequences of the undesirable immune response initiated by gluten peptides. We show that CD is a model disease to decipher the role of MHC class II molecules in human immunopathology, to analyze the mechanisms that link tolerance to food proteins and autoimmunity, and to investigate how chronic activation of IEL can lead to T cell lymphomagenesis.
Immunity 06/2012; 36(6):907-19. · 21.64 Impact Factor
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Corinne Lebreton,
Sandrine Ménard,
Juliette Abed,
Ivan Cruz Moura,
Rosanna Coppo,
Christophe Dugave,
Renato C Monteiro,
Aurélie Fricot,
Meriem Garfa Traore,
Martin Griffin,
Christophe Cellier, Georgia Malamut,
Nadine Cerf-Bensussan,
Martine Heyman
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ABSTRACT: The transferrin receptor (CD71) is up-regulated in duodenal biopsy samples from patients with active celiac disease and promotes retrotransport of secretory immunoglobulin A (SIgA)-gliadin complexes. We studied intestinal epithelial cell lines that overexpress CD71 to determine how interactions between SIgA and CD71 promote transepithelial transport of gliadin peptides.
We analyzed duodenal biopsy specimens from 8 adults and 1 child with active celiac disease. Caco-2 and HT29-19A epithelial cell lines were transfected with fluorescence-labeled small interfering RNAs against CD71. Interactions among IgA, CD71, and transglutaminase 2 (Tgase2) were analyzed by flow cytometry, immunoprecipitation, and confocal microscopy. Transcytosis of SIgA-CD71 complexes and intestinal permeability to the gliadin 3H-p31-49 peptide were analyzed in polarized monolayers of Caco-2 cells.
Using fluorescence resonance energy transfer and in situ proximity ligation assays, we observed physical interactions between SIgA and CD71 or CD71 and Tgase2 at the apical surface of enterocytes in biopsy samples and monolayers of Caco-2 cells. CD71 and Tgase2 were co-precipitated with SIgA, bound to the surface of Caco-2 cells. SIgA-CD71 complexes were internalized and localized in early endosomes and recycling compartments but not in lysosomes. In the presence of celiac IgA or SIgA against p31-49, transport of intact 3H-p31-49 increased significantly across Caco-2 monolayers; this transport was inhibited by soluble CD71 or Tgase2 inhibitors.
Upon binding to apical CD71, SIgA (with or without gliadin peptides) enters a recycling pathway and avoids lysosomal degradation; this process allows apical-basal transcytosis of bound peptides. This mechanism is facilitated by Tgase2 and might be involved in the pathogenesis of celiac disease.
Gastroenterology 06/2012; 143(3):698-707.e1-4. · 11.68 Impact Factor
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Georgia Malamut,
Virginie Verkarre,
Céline Callens,
Orianne Colussi,
Gabriel Rahmi,
Elizabeth MacIntyre,
Corinne Haïoun,
Bertrand Meresse,
Nicole Brousse,
Serge Romana,
Olivier Hermine,
Nadine Cerf-Bensussan,
Christophe Cellier
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ABSTRACT: Enteropathy-associated T-cell lymphoma (EATL) is a rare non-Hodgkin lymphoma frequently associated with celiac disease. We report a case of EATL complicating adult autoimmune enteropathy (AIE). Analysis of phenotype, rearrangements in T-cell receptor genes, and chromosome alterations by high-resolution comparative genomic hybridization identified features distinct from those described for types I and II EATL. Furthermore, EATL arose from a single T-cell clone that had been present for several years in AIE-associated, oligoclonal, intestinal T-cell infiltrate. Emerging T-cell clones should be monitored in patients with AIE who receive long-term immunosuppressive therapy.
Gastroenterology 01/2012; 142(4):726-729.e3; quiz e13-4. · 11.68 Impact Factor
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Sandrine Ménard,
Corinne Lebreton,
Michael Schumann,
Tamara Matysiak-Budnik,
Christophe Dugave,
Yoram Bouhnik, Georgia Malamut,
Christophe Cellier,
Matthieu Allez,
Pascal Crenn,
Joerg Dieter Schulzke,
Nadine Cerf-Bensussan,
Martine Heyman
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ABSTRACT: The intestinal permeability of undegraded α9-gliadin peptide 31-49 (p31-49) and 33-mer gliadin peptides is increased in active celiac disease. Two distinct transport pathways have been proposed: paracellular leakage through epithelial tight junctions and protected transcellular transport. To analyze the relative contribution of these pathways, we compared mucosa-to-serosa permeability of small and large permeability markers [ionic conductance (G), mannitol, 182 Da; horseradish peroxidase, 40 kDa] and gliadin peptides [33-mer (p56-88, 3900 Da), 19-mer (p31-49, 2245 Da; and p202-220, 2127 Da), and 12-mer (p57-68, 1453 Da)] in duodenal biopsy specimens mounted in Ussing chambers. The permeability of intact peptides was much higher for p31-49 or 33-mer than for horseradish peroxidase, p202-220, and p57-68. A positive correlation was observed between G, an index of paracellular diffusion of ions, and mannitol permeability. The absence of correlation between G and permeability to intact 33-mer or p31-49 did not favor paracellular diffusion of the peptides. Immunofluorescence studies indicated that 33-mer enters the early endosome antigen 1-positive compartment but escapes the lysosomal-associated protein 2-positive compartment. The results underline that mannitol and ionic conductance G cannot be considered markers of permeability to gliadin peptides. In active celiac disease, increases in transcellular permeability to intact gliadin peptides might be considered in treatment strategies aimed at controlling epithelial permeability to gluten.
American Journal Of Pathology 11/2011; 180(2):608-15. · 4.89 Impact Factor
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ABSTRACT: Refractory celiac disease (RCD) is subdivided into two subtypes (RCDI and II), based on a normal or abnormal phenotype of intraepithelial lymphocytes, respectively. RCDII is the most severe form and seems to be more frequently observed in Europe than in the United States. We discussed below the diagnostic criteria of RCDI and RCDII, and the possible factors underlying the more severe expression of celiac disease in Europe.
The American Journal of Gastroenterology 05/2011; 106(5):929-32. · 7.28 Impact Factor
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Georgia Malamut,
Virginie Verkarre,
Felipe Suarez,
Jean-François Viallard,
Anne-Sophie Lascaux,
Jacques Cosnes,
Yoram Bouhnik,
Olivier Lambotte,
Dominique Béchade,
Marianne Ziol,
Anne Lavergne,
Olivier Hermine,
Nadine Cerf-Bensussan,
Christophe Cellier
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ABSTRACT: The enteropathy associated with common variable immunodeficiency (CVID) is poorly characterized, and its possible relationships with well-defined causes of enteropathy, such as celiac sprue (CS), remain debated. We aimed to assess the clinical and histopathological features of the enteropathy associated with CVID.
The medical files of 50 CVID patients with gastrointestinal symptoms were analyzed retrospectively. Histological, phenotypic, and molecular analysis of intestinal endoscopic specimens was centrally performed.
Chronic diarrhea was the most frequent gastrointestinal symptom (92%), and biological evidence of malabsorption was observed in 54% of patients. Chronic gastritis associated or not with pernicious anemia and microscopic colitis were the most frequently observed histopathological features in gastric and colonic mucosa, respectively. Small-bowel biopsies available in 41 patients showed moderate increase in intestinal intraepithelial lymphocytes in 31 patients (75.6%) and villous atrophy in 21 patients (51%). Distinctive features from CS were a profound depletion in plasma cells and follicular lymphoid hyperplasia. Presence of peripheral blood CD8+ hyperlymphocytosis was predictive of intestinal intraepithelial hyperlymphocytosis. Intravenous (i.v.) immunoglobulin (Ig) therapy had no effect on enteropathy-related symptoms. Gluten-free diet improved only two out of 12 patients with villous atrophy, whereas all patients (7/7) responded to steroid therapy.
Several distinctive features differentiate CVID enteropathy from other causes of enteropathy including CS. Replacement i.v. Ig therapy is insufficient to improve gastrointestinal symptoms. Steroids are effective in reducing inflammation and restoring mucosal architecture.
The American Journal of Gastroenterology 10/2010; 105(10):2262-75. · 7.28 Impact Factor
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Georgia Malamut,
Raja El Machhour,
Nicolas Montcuquet,
Séverine Martin-Lannerée,
Isabelle Dusanter-Fourt,
Virginie Verkarre,
Jean-Jacques Mention,
Gabriel Rahmi,
Hiroshi Kiyono,
Eric A Butz,
Nicole Brousse,
Christophe Cellier,
Nadine Cerf-Bensussan,
Bertrand Meresse
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ABSTRACT: Enteropathy-associated T cell lymphoma is a severe complication of celiac disease (CD). One mechanism suggested to underlie its development is chronic exposure of intraepithelial lymphocytes (IELs) to potent antiapoptotic signals initiated by IL-15, a cytokine overexpressed in the enterocytes of individuals with CD. However, the signaling pathway by which IL-15 transmits these antiapoptotic signals has not been firmly established. Here we show that the survival signals delivered by IL-15 to freshly isolated human IELs and to human IEL cell lines derived from CD patients with type II refractory CD (RCDII) - a clinicopathological entity considered an intermediary step between CD and enteropathy-associated T cell lymphoma - depend on the antiapoptotic factors Bcl-2 and/or Bcl-xL. The signals also required IL-15Rbeta, Jak3, and STAT5, but were independent of PI3K, ERK, and STAT3. Consistent with these data, IELs from patients with active CD and RCDII contained increased amounts of Bcl-xL, phospho-Jak3, and phospho-STAT5. Furthermore, incubation of patient duodenal biopsies with a fully humanized human IL-15-specific Ab effectively blocked Jak3 and STAT5 phosphorylation. In addition, treatment with this Ab induced IEL apoptosis and wiped out the massive IEL accumulation in mice overexpressing human IL-15 in their gut epithelium. Together, our results delineate the IL-15-driven survival pathway in human IELs and demonstrate that IL-15 and its downstream effectors are meaningful therapeutic targets in RCDII.
The Journal of clinical investigation 06/2010; 120(6):2131-43. · 15.39 Impact Factor
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The American Journal of Gastroenterology 05/2009; 104(4):1069. · 7.28 Impact Factor
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Georgia Malamut,
Pauline Afchain,
Virginie Verkarre,
Thierry Lecomte,
Aurélien Amiot,
Diane Damotte,
Yoram Bouhnik,
Jean-Frédéric Colombel,
Jean-Charles Delchier,
Matthieu Allez,
Jacques Cosnes,
Anne Lavergne-Slove,
Bertrand Meresse,
Ludovic Trinquart,
Elizabeth Macintyre,
Isabelle Radford-Weiss,
Olivier Hermine,
Nicole Brousse,
Nadine Cerf-Bensussan,
Christophe Cellier
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ABSTRACT: Refractory celiac disease (RCD) was recently subdivided into 2 subtypes (RCD I and II) based on a normal or abnormal phenotype of intraepithelial lymphocytes (IELs), respectively. It is not clear, however, if these 2 entities differ in their presentation at diagnosis or long-term outcome. We compared the clinical and biological characteristics of RCD I and RCD II at diagnosis, the risk of developing an overt lymphoma, and the predictive factors of survival.
Medical files of 14 patients with RCD I and 43 with RCD II were analyzed retrospectively. Predictive factors of overt lymphoma and survival were studied in univariate and multivariate analyses.
At diagnosis, malnutrition, ulcerative jejunitis, and lymphocytic gastritis were more common in patients with RCD II than RCD I (P< .05). Overt lymphomas occurred in 2 patients with RCD I and 16 with RCD II. In the univariate analysis, abnormal IEL phenotype and increased age at diagnosis of RCD were predictive factors for overt lymphoma. Abnormal IEL phenotype (P< .01), clonality (P= .01), and overt lymphoma (P= .001) predicted short survival time. Only abnormal IEL phenotype (P= .03) and overt lymphoma (P= .04) were predictive in the multivariate analysis. The 5-year survival rate was 93% in patients with RCD I and 44% with RCD II.
RCD II has a much more severe presentation and prognosis than patients with RCD I; <44% of patients with RCD II survive 5 years after diagnosis. Abnormal IEL phenotype is a predictive factor but not a necessary condition for the development of overt lymphoma.
Gastroenterology 10/2008; 136(1):81-90. · 11.68 Impact Factor
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ABSTRACT: Celiac disease is an enteropathy due to gluten intake in genetically predisposed persons (HLA DQ2/DQ8). Celiac disease occurs in adults and children at rates approaching 1% of population in Europe and USA. Clinical presentation of celiac disease is extremely varied. Anaemia, oral aphthous stomatis, amenorrhea or articular symptoms may reveal celiac disease. Diagnosis relies on evidence of duodenal villous atrophy and specific serum antibodies. Treatment relies on eviction of gluten (wheat, barley, rye). Gluten-free diet allows prevention of malignant complications and osteopenia. The main cause of resistance to gluten-free diet is its bad observance. On the contrary, serious complications of celiac disease, such as clonal refractory celiac sprue and intestinal T cell lymphoma need to be screen.
La Revue du praticien 07/2008; 58(11):1199-205.
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Tamara Matysiak-Budnik,
Ivan Cruz Moura,
Michelle Arcos-Fajardo,
Corinne Lebreton,
Sandrine Ménard,
Céline Candalh,
Karima Ben-Khalifa,
Christophe Dugave,
Houda Tamouza,
Guillaume van Niel,
Yoram Bouhnik,
Dominique Lamarque,
Stanislas Chaussade, Georgia Malamut,
Christophe Cellier,
Nadine Cerf-Bensussan,
Renato C Monteiro,
Martine Heyman
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ABSTRACT: Celiac disease (CD) is an enteropathy resulting from an abnormal immune response to gluten-derived peptides in genetically susceptible individuals. This immune response is initiated by intestinal transport of intact peptide 31-49 (p31-49) and 33-mer gliadin peptides through an unknown mechanism. We show that the transferrin receptor CD71 is responsible for apical to basal retrotranscytosis of gliadin peptides, a process during which p31-49 and 33-mer peptides are protected from degradation. In patients with active CD, CD71 is overexpressed in the intestinal epithelium and colocalizes with immunoglobulin (Ig) A. Intestinal transport of intact p31-49 and 33-mer peptides was blocked by polymeric and secretory IgA (SIgA) and by soluble CD71 receptors, pointing to a role of SIgA-gliadin complexes in this abnormal intestinal transport. This retrotranscytosis of SIgA-gliadin complexes may promote the entry of harmful gliadin peptides into the intestinal mucosa, thereby triggering an immune response and perpetuating intestinal inflammation. Our findings strongly implicate CD71 in the pathogenesis of CD.
Journal of Experimental Medicine 02/2008; 205(1):143-54. · 13.85 Impact Factor
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Georgia Malamut,
Marianne Ziol,
Felipe Suarez,
Michel Beaugrand,
Jean François Viallard,
Anne Sophie Lascaux,
Virginie Verkarre,
Dominique Bechade,
Thierry Poynard,
Olivier Hermine,
Christophe Cellier
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ABSTRACT: Liver lesions associated with primary hypogammaglobulinemia have been poorly described. We aimed to assess the clinical, histological and immune features and outcome of hepatic injury in patients with primary hypogammaglobulinemia.
The medical records of 51 patients (23 patients with liver biopsy) with primary hypogammaglobulinemia and liver abnormalities were retrospectively reviewed. Forty-three controls with primary hypogammaglobulinemia but with no hepatic manifestations were analyzed in parallel.
Cholestasis (65%), mainly anicteric, and portal hypertension (50%) were the main hepatic manifestations. Histological analysis revealed non-fibrosing architectural abnormalities consistent with nodular regenerative hyperplasia (NRH) in 84% of CVID patients and in all HIGM and XLA patients. Intrasinusoidal lymphocytic infiltration, abnormalities of portal vessels and epithelioid granulomas were observed in 90%, 43% and 44% of patients, respectively. NRH was associated with portal hypertension in 75% of the cases. These patients more often presented with autoimmune diseases and peripheral lymphocytic abnormalities than control patients (p < 0.05).
Liver involvement in primary hypogammaglobulinemia mainly consists of NRH leading to chronic cholestasis and portal hypertension. Association with intrasinusoidal T cell infiltration, portal vein endotheliitis, autoimmune diseases and peripheral lymphocytic abnormalities suggests an autoimmune mechanism.
Journal of Hepatology 01/2008; 48(1):74-82. · 9.26 Impact Factor
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ABSTRACT: Gastrointestinal symptoms are common and often reveal primary immunodeficiency. Although they mimic gastrointestinal diseases observed in immunocompetent patients, there have diagnostic and therapeutic specificities that should be known for optimal management of these patients. This review describes the gastrointestinal diseases found in primary immunodeficiency and proposes some diagnostic and therapeutic strategies.
Gastroentérologie Clinique et Biologique 11/2007; 31(10):844-53. · 0.80 Impact Factor
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ABSTRACT: Whether a life-long gluten-free diet (GFD) is necessary in all children with diagnosed coeliac disease (CD) remains debated. To address this question, a retrospective analysis of the clinical and biological status of adult coeliac patients diagnosed in childhood, who remained on a normal diet after gluten challenge and were clinically silent, was carried out.
Patients aged 18-65 years with CD diagnosed in childhood were included. Clinical status, gluten intake, biological parameters of malabsorption, bone mineral density, human leucocyte antigen (HLA) genotype, serological markers of CD, and histological and immunohistochemical parameters in duodenal biopsies were recorded.
Sixty-one patients had resumed a normal diet and were asymptomatic. Forty-eight showed different degrees of villous atrophy (silent CD), while 13 had no detectable atrophy (latent CD) on duodenal biopsies. Latent CD patients had significantly less osteopenia/osteoporosis (1/9 (11%) vs 23/33 (70%), p<0.001)), and lower T cell receptor (TCR) alphabeta+ intraepithelial T cell counts (38+/-20 vs 55+/-15, p<0.01) than silent CD patients. The mean age at diagnosis and first GFD was lower in latent than in silent patients (14.4+/-5 vs 40.1+/-47 months, p<0.05). Latent patients did not differ significantly from the seven control patients on a long-term GFD, except for a higher frequency of CD-specific serum antibodies. However, two latent patients relapsed clinically and histologically during subsequent follow-up.
Long-term latency developed in about 20% of CD patients who remained symptom free after gluten reintroduction. This latency can be transient and thus a regular follow-up is mandatory. In silent patients, the increased risk of osteoporosis substantiates the need for a GFD.
Gut 11/2007; 56(10):1379-86. · 10.11 Impact Factor
