Are Complicated Forms of Celiac Disease Cryptic T-Cell Lymphomas?

We assessed the clonality of duodenal mucosal T cells in patientswith celiac disease and controls. Fifteen adult patients were studied.Four patients had a complicated celiac disease, 3 did not respond to agluten-free diet, and 2 had an ulcerative jejunitis (including 1 patient with nonresponsive celiac disease). Seven patients had anuntreated celiac disease responsive to a gluten-free diet. Histologicalexamination of duodenal biopsies of these 11 patients showedbenign-appearing celiac disease without evidence of lymphoma. Fourpatients with nonulcer dyspepsia and normal duodenal biopsies served ascontrols. TCR gene rearrangements were analyzed by multiplexpolymerase chain reaction on DNA extracted from duodenal biopsies.Major clonal rearrangements of the T-cell receptor were found in 4 cases, all with complicated celiac disease. Monoclonality was confirmedby DNA sequencing of the junctional region in 3 cases and byhybridization with clone-specific oligoprobes. Patients with celiacdisease responsive to gluten-free diet had mainly a polyclonal pattern,with 1 of them having an oligoclonal rearrangement. An oligoclonalpattern was also observed in 2 control patients. Three patients withcomplicated celiac disease evolved to T-cell lymphoma with liver (n = 2) or bone marrow (n = 1) invasion. Identical clones were found inthe enteropathic duodenojejunum and peripheral blood in the patientwith large-cell lymphoma with bone marrow invasion. This study suggeststhat complicated celiac disease is a cryptic T-cell lymphoma.     

Helicobacter pylori infection in patients with celiac disease

BACKGROUND AND AIMS: Patients with Helicobacter pylori gastritis are more likely to have increased duodenal intraepithelial lymphocytes (IEL); this can be reversed by H. pylori eradication. We hypothesized that: (1) H. pylori-infected celiac disease (CD) patients could have different clinicopathological features from noninfected subjects; and (2) the histopathological responses to a gluten-free diet could be different in H. pylori-infected and noninfected patients. METHODS: Duodenal and gastric biopsies obtained from 80 adults with histologically and serologically confirmed CD before and after 12-18 months of a gluten-free diet were retrospectively evaluated. Gastritis was classified and scored according to the Updated Sydney System; duodenal biopsies were classified using both the Marsh-Oberhuber and a simplified classification proposed by our group. RESULTS: At baseline, 30 patients had H. pylori infection and 50 did not; at follow-up five new infections were detected. Fifteen patients (3 H. pylori-positive and 12 negative) had lymphocytic gastritis. At baseline, a greater proportion of H. pylori-negative patients had severe villous atrophy (p < 0.01), but milder forms were more prevalent in H. pylori-positive patients (p < 0.01). After a gluten-free diet, significant improvement occurred in all duodenal features (p < 0.001), irrespective of H. pylori status; gastric variables did not change, except for lymphocytic, which resolved in 2 infected and 10 noninfected patients. CONCLUSIONS: The clinical features of CD patients are unrelated to H. pylori gastritis, and a gluten-free diet is equally effective in infected as in uninfected patients. The higher prevalence of milder duodenal lesions in CD patients with H. pylori infection suggests that lymphocytosis induced by H. pylori gastric infection becomes less obvious as profound inflammatory and structural changes alter the mucosal architecture. This study also provides further support for a pathogenetic relationship between CD and lymphocytic gastritis.     

What is the role of celiac disease in enteropathy-type intestinal lymphoma? A retrospective study of nine cases

BACKGROUND AND AIMS: It is generally accepted that enteropathy-type intestinal lymphoma (EATL) arises against a background of gluten enteropathy. We investigate whether patients with this diagnosis had celiac disease or pre-existing celiac disease, based on gliadin and endomysium antibodies, as well as duodenal biopsies, HLA typing and response to gluten-free diet. METHODS AND RESULTS: Retrospective study of patients with the diagnosis of peripheral T cell lymphoma of the intestine between January 1990 and January 2002 at the university hospital Gasthuisberg Leuven (n = 14). Patients in whom serologic testing was performed or patients known with pre-existing celiac disease (CD) were included (n = 9). Six of these nine patients were tested for endomysium antibodies (AEM), none of them were positive. Of the six patients with biopsies of mucosa uninvolved by lymphoma, all of them had villous atrophy; five had increased intraepithelial lymphocytes (IEL). In the four patients were HLA typing was performed, the results were compatible with CD. The three patients with initially diagnosed celiac disease all improved on gluten free diet (control biopsies improved as well, but failed to normalise). Of the six other patients, one patient never started GFD, two didn't get better, one initially went better after GFD, and one went better with the concomitantly started chemotherapy. CONCLUSION: There are two possible explanations: Either these patients with EATL have indeed gluten intolerance but the sensitivity of AEM is overestimated in this patient population; or these patients don't have gluten intolerance and EATL itself can mimic CD or other factors mimicking CD are at risk for developing EATL.     

Cell Density Counts of the Intestinal Intraepithelial Lymphocytes in the Celiac Patients

Background: Increased number of intestinal intraepithelial lymphocytes (IELs) is a key histological finding in the diagnosis of celiac disease (CD); however, the number of IELs in celiac patients and healthy subjects may vary from one region to another. Additionally, there are some seronegative celiac patients with a borderline histology. Objective: To determine the number of the CD3+ and CD8+ IELs T-cells in the celiac patients and healthy subjects (controls) in Isfahan. Methods: The duodenal biopsies were obtained from the celiac patients (n=15) and the controls (n=19). The total number of IELs/100 epithelial cells (ECs) were counted using the hematoxylin-eosin (H&E) staining method, and that of CD3+ and CD8+ IELs/100 ECs were counted using the immunohistochemistry (IHC) staining method. Results: This study defined the upper normal limit for each variable as mean + 2SD. Accordingly, the upper normal limits of the total IELs, CD3+ IELs, and CD8+  IELs/100 ECs were calculated as 37 (95% confidence intervals, CI: 33–41), 22 (95% CI: 19–25) and 12 (95% CI: 10–14), respectively. In 3 clinically CD diagnoses, the total IELs counts/100 ECs were below the upper normal limit, and the histopathological and serologic assays were negative. Nevertheless, the CD8+ IELs T-cells counts/100 ECs showed borderline values. Interestingly, these patients responded to a gluten-free diet (GFD). Conclusions: The study findings suggest that in the clinically diagnosed celiac disease, IELs count/100 ECs below the upper normal limit as well as negative histopathological and serologic assays and the cell density counts of the CD8+ IELs T-cells/100 ECs could be a useful parameter for CD diagnosis and make a decision to put them on a GFD.     

Efficacy of gluten-free diet alone on recovery from iron deficiency anemia in adult celiac patients

OBJECTIVE: Iron deficiency anemia has been reported as the most frequent extraintestinal symptom in adult celiac disease. Prospective studies on the effect of gluten-free diet on recovery from iron deficiency anemia are lacking. The aim of this study was to verify in adult patients with celiac disease the efficacy of and the time course of recovery from iron deficiency anemia by a gluten-free diet alone. METHODS: We studied 190 consecutive adult patients with iron deficiency anemia, screened for celiac disease by duodenal biopsies. New diagnosed celiac patients were invited to follow a gluten-free diet alone without iron supplementation. After 6 months of diet, duodenal biopsies were performed and hematological tests were repeated at 6, 12, and 24 months. RESULTS: Celiac disease was diagnosed in 26 (24 women, 2 men; 13.7%) adult patients. After 6 months of gluten-free diet 14 of 18 (77.8%) female patients recovered from anemia, but only 5 of 18 (27.8%) reversed from iron deficiency. At 12-month control all but one patient (94.4%) recovered from anemia and 9 patients (50%) from iron deficiency. After 24 months of diet, only the patient who did not recover from anemia at 12-month control was still anemic, whereas 10 patients (55.5%) reversed from iron deficiency. A significant inverse correlation (r = -0.7141, p = 0.0003) between increase of Hb concentrations and decrease of individual histological scores of duodenitis was observed. CONCLUSIONS: A screening for celiac disease should be carried out in adult patients with iron deficiency anemia. Recovery from anemia occurs between 6 and 12 months on a gluten-free diet alone as a consequence of normalization of histological alterations of the intestinal mucosa.     

A Brazilian experience of the self transglutaminase-based test for celiac disease case finding and diet monitoring

AIM： To evaluate the effectiveness of a rapid and easy fingertip whole blood point-of-care test for celiac disease （CD） case finding and diet monitoring. METHODS： Three hundred individuals, 206 females （68.7%） and 94 males （31.3%）, were submitted to a rapid and easy immunoglobulin-A-dass fingertip whole blood point-of-care test in the doctor＇s office in order to make immediate clinical decisions： 13 healthy controls, 6 with CD suspicion, 46 treated celiacs, 84 relatives of the celiac patients, 69 patients with dyspepsia, 64 with irritable bowel syndrome （IBS）, 8 with Crohn＇s disease and 9 with other causes of diarrhea. RESULTS： Upper gastrointestinal endoscopy with duodenal biopsies was performed in patients with CD suspicion and in individuals with positive test outcome： in 83.3% （5/6） of the patients with CD suspicion, in 100% of the patients that admitted gluten-free diet transgressions （6/6）, in 3.8% of first-degree relatives （3/79） and in 2.9% of patients with dyspepsia （2/69）. In all these individuals duodenal biopsies confirmed CD （Marsh＇s histological classification）. The studied test showed good correlation with serologic antibodies, endoscopic and histological findings.CONCLUSION： The point-of-care test was as reliable as conventional serological tests in detecting CD cases and in CD diet monitoring.     

Magnitude of CD8+ T-cell responses against hepatitis C virus and severity of hepatitis do not necessarily determine outcomes in acute hepatitis C virus infection

Aim:  We investigated the relationship between the magnitude of comprehensive hepatitis C virus (HCV)-specific CD8⁺ T-cell responses and the clinical course of acute HCV infection.
Methods:  Six consecutive patients with acute HCV infection were studied. Analysis of HCV-specific CD8⁺ T-cell responses was performed using an interferon-γ-based enzyme-linked immunospot assay using peripheral CD8⁺ T-cells, monocytes and 297 20-mer synthetic peptides overlapping by 10 residues and spanning the entire HCV sequence of genotype 1b.
Results:  Five patients presented detectable HCV-specific CD8⁺ T-cell responses against a single and different peptide, whereas 1 patient showed responses against three different peptides. Neither the magnitude of HCV-specific CD8⁺ T-cell responses nor the severity of hepatitis predicts the outcome of acute hepatitis. The maximum number of HCV-specific CD8⁺ T-cells correlated with maximum serum alanine aminotransferase level during the course ( r  = 0.841, P  = 0.036).
Conclusions:  HCV-specific CD8⁺ T-cell responses were detectable in all 6 patients with acute HCV infection, and 6 novel HCV-specific CTL epitopes were identified. Acute HCV infection can resolve with detectable HCV-specific CD8⁺ T-cell responses, but without development of antibody against HCV.     

Duodenal histology in patients with celiac disease after treatment with a gluten-free diet

BACKGROUND: The diagnosis of celiac disease requires characteristic histopathologic changes in an intestinal biopsy with clinical improvement in response to a gluten-free diet. Endoscopy with procurement of biopsy specimens is often performed to document response to the diet, but there are little data on the appearance of treated celiac disease. This study examined the endoscopic and histopathologic appearance of the duodenum of patients with celiac disease whose diet was gluten-free. METHODS: A cohort of 39 adult patients (mean age 52 years, range 20-74 years) with biopsy-proven celiac disease was retrospectively reviewed. All had responded clinically to a gluten-free diet that they had maintained for a mean of 8.5 years (range 1-45 years). The endoscopic and histopathologic appearances of the duodenal mucosa were reviewed. Blinded review of the diagnostic (initial) and post-treatment biopsy specimens was also performed to assess response of individual patients to the diet. RESULTS: The endoscopic appearance was normal in 23%, reduced duodenal folds were present in 46%, scalloping of folds in 33%, mucosal fissures in 44%, and nodularity in 33%. There was more than 1 abnormality present in 46%. Histology was normal in only 21%. The remainder had villous atrophy (69% partial, 10% total). Paired (diagnostic and follow-up) biopsy specimens were reviewed blindly for 12 patients. The mean (SD) intraepithelial lymphocyte count fell from 61 (22) to 38 (17) (normal <30 per 100 epithelial cells) and the crypt-to-villous ratio improved although it did not normalize. CONCLUSIONS: Despite a good clinical response, abnormal endoscopic and histopathologic appearances persist in the majority of patients with celiac disease treated with a gluten-free diet.     

Antroduodenojejunal motor activity in untreated and treated celiac disease patients

Background and Aim:  Patients with celiac disease may present with abnormal upper gut motor activity. However, it is not known if these abnormalities persist after the introduction of a gluten-free diet. The present study aimed to compare antroduodenojejunal motor variables recorded in untreated celiac patients with those of celiac patients given a gluten-free diet and healthy volunteers.
Methods:  Eleven untreated celiac disease patients, 12 age- and sex-matched celiac patients on a gluten-free diet (at least 12 months), and 33 controls entered the study. Antroduodenojejunal motility was recorded for 6 h during fasting and for 3 h after a standard meal by means of a perfused, multiple lumen catheter.
Results:  More than 80% of untreated celiac patients had discrete motor abnormalities of the upper gut, in both fasting and fed recordings, compared to the other subjects. Patients on a gluten-free diet also showed motor abnormalities, albeit to a lesser extent. In these patients histological evaluation showed the persistence of mild mucosal abnormalities.
Conclusions:  Upper gut motor abnormalities are frequent in patients with celiac disease, even in those on a gluten-free diet. In the latter group, these abnormalities may suggest an incomplete adherence to the dietary regimen.     

Immunophenotype of c-kit cells in normal human bone marrow: implications for the detection of minimal residual disease in AML

Summary. In the present study, seven normal human bone marrow samples from healthy volunteers have been analysed in order to investigate the immunophenotypic characteristics of the normal CD117⁺ cells and their utility for the detection of minimal residual disease in 71 acute myeloid leukaemia patients.
Our results show that most of normal BM CD117⁺ cells coexpress the HLADR and the myeloid associated CD33 antigen. In addition, almost half of CD117⁺ cells are CD34⁺, these cells displaying a different FSC/SSC distribution when compared to the CD117⁺/CD34⁻ cells. No CD117⁺/CD15⁺ and CD117⁺/CD10⁺ cells were detected and very few CD117⁺ cells (<1 × 10⁻³) expressing the HLADR⁻/CD34⁻, CD33⁺/HLADR⁻ and CD34⁺/HLADR⁻ phenotypes were found to be present in normal BM. In contrast, from the 71 AML patients analysed, 34 had CD117⁺/CD15⁺ blast cells and eight had the CD117⁺ phenotypes detected at low frequencies (<1 × 10⁻³) in normal BM.
In summary, the present study shows that the use of the CD117 antigen in different monoclonal antibodies combinations may be of great help for the detection of minimal residual disease in a high proportion of AML cases, especially in those patients displaying the CD117⁺/CD15⁺ phenotype, because cells coexpressing both antigens in normal BM, if present, are at very low frequencies.     

Monitoring of CD95 and CD38 expression in peripheral blood T lymphocytes during active human cytomegalovirus infection after orthotopic liver transplantation

Aim:  The aim of the present study was to quantitatively monitor the response of CD95 molecules expressed on CD3⁺ T cells (CD95⁺CD3⁺ cells) and CD38 molecules expressed on CD8⁺ T cells (CD38⁺CD8⁺ cells) to ganciclovir treatment after orthotopic liver transplant (OLT) in recipients with active human cytomegalovirus (HCMV) infection.
Methods:  Blood samples were collected from 20 liver transplanted recipients with active HCMV infection and 24 recipients without HCMV infection. CD95⁺CD3⁺ cells and CD38⁺CD8⁺ cells were quantitatively detected with QuantiBRITE bead methods by dual-color flow cytometry analysis during the post-transplantation period.
Results:  CD95⁺CD3⁺ cells and CD38⁺CD8⁺ cells were not significantly different among different ages of healthy adults ( P  > 0.05). CD95⁺CD3⁺ cells and CD38⁺CD8⁺ cells were drastically increased in the active HCMV infection group compared with that in the stable group or in the healthy group ( P  < 0.001), and then they were gradually decreased within the next several weeks after ganciclovir treatment when compared with active HCMV infection recipients ( P  < 0.001).
Conclusions:  The present study showed that CD38⁺CD8⁺ T cells can be an appropriate immunological marker for early detection and antiviral therapeutic monitoring of HCMV infection. The evaluation of CD95 molecule levels may be used routinely in clinical practice to assess the level of immunosuppression.     

Cervical esophageal web and celiac disease

Background and Aim:  There is paucity of prospective data on association between cervical esophageal webs and celiac disease. It is not clear whether all patients with cervical esophageal web need screening for celiac disease. Hence, the present study was carried out to determine the association of cervical esophageal web with celiac disease.
Methods:  This prospective study included consecutive patients with symptomatic cervical esophageal web diagnosed over a period of 4.5 years. Tissue transglutaminase antibody was measured in serum of each patient. Patients with elevated tissue transglutaminase antibody titer were subjected to esophagogastroduodenoscopy and biopsies were obtained from the descending duodenum to look for histological changes of celiac disease. Esophageal web was treated with bougie dilatation. Celiac disease was diagnosed on the basis of elevated tissue transglutaminase antibody and suggestive duodenal histology.
Results:  Twenty one patients were diagnosed to have cervical esophageal web. Eighteen (85.7%) had evidence of iron deficiency. Five (23.8%) patients with cervical esophageal web fulfilled criteria for diagnosis of celiac disease. All five had evidence of iron deficiency. None of these patients gave a history of chronic diarrhea. All patients were treated with bougie dilatation. Patients with celiac disease were advised of a gluten-free diet. All five celiac disease patients are free of dysphagia without recurrence after a mean follow up of 10 months (range: 3 to 16 months).
Conclusions:  There is association between cervical esophageal web and celiac disease. All adult patients with cervical esophageal web and iron deficiency need screening for celiac disease even in the absence of chronic diarrhea.     

Foxp3 expression on normal and leukemic CD4+CD25+ T cells implicated in human T-cell leukemia virus type-1 is inconsistent with Treg cells

Foxp3 is a master gene of Treg cells, a novel subset of CD4⁺ T cells primarily expressing CD25. We describe here different features in Foxp3 expression profile between normal and leukemic CD4⁺CD25⁺ T cells, using peripheral blood samples from healthy controls (HCs), human T-cell leukemia virus type-1 (HTLV-1)-infected asymptomatic carriers (ACs), patients with adult T-cell leukemia (ATL), and various hematopoietic cell lines. The majority of CD4⁺CD25⁺ T cells in HCs were positive for Foxp3, but not all CD4⁺CD25⁺ T cells in ACs were positive, indicating that Foxp3 expression is not always linked to CD25 expression in normal T cells. Leukemic (ATL) T cells constitutively expressing CD25 were characteristic of heterogeneous Foxp3 expression, such as intra- and inter-case heterogeneity in intensity, inconsistency with CD25 expression, and a discrepancy in the mRNA and its protein expression. Surprisingly, a discernible amount of Foxp3 mRNA was detectable even in most cell lines without CD25 expression, a small fraction of which was positive for the Foxp3 proteins. The subcellular localization of Foxp3 in HTLV-1-infected cell lines was mainly cytoplasmic, different from that of primary ATL cells. These findings indicate that Foxp3 has two facets: essential Treg identity and molecular mimicry secondary to tumorigenesis. Conclusively, Foxp3 in normal T cells, but not mRNA, is basically potent at discriminating a subset of Treg cells from CD25⁺ T-cell populations, whereas the modulation of Foxp3 expression in leukemic T cells could be implicated in oncogenesis and has a potentially useful clinical role.     

Celiac disease-like abnormalities in a subgroup of patients with irritable bowel syndrome.

BACKGROUND & AIMS: Abdominal symptoms in the absence of mucosal abnormalities are features of both the irritable bowel syndrome (IBS) and latent/potential celiac disease (cd). To identify a possible subgroup of IBS patients with latent/potential cd, surrogate markers of cd were investigated in IBS patients. METHODS: IBS patients suffering from diarrhea (n = 102), and patients with active cd (n = 10), treated cd (n = 26), and latent cd (n = 5) were included in the study. We measured serum immunoglobulin (Ig) A against gliadin and tissue-transglutaminase, and IgA and IgM against gliadin, tissue-transglutaminase (intestinal cd-associated antibodies), and the dietary proteins beta-lactoglobulin and ovalbumin in duodenal aspirate by enzyme-linked immunosorbent assay. Intraepithelial lymphocytes (IELs) were counted in histology sections, and the expression of HLA-DQ2 (A1*0501/B1*0201) was investigated by polymerase chain reaction. In 26 IBS patients, the effect of 6 months of gluten withdrawal was examined. RESULTS: Most cd patients expressed HLA-DQ2 and had increased intestinal cd-associated antibodies, whereas cd-associated serum IgA and IEL counts were increased in active cd in contrast to treated or latent cd. In IBS patients, 35% were HLA-DQ2-positive, 23% had increased IEL counts, and 0% and 30% had increased cd-associated antibodies in serum and duodenal aspirate, respectively. Furthermore, stool frequency and intestinal IgA decreased significantly under a gluten-free diet in the subgroups of HLA-DQ2-positive and intestinal antibody-positive IBS patients when compared with IBS patients without these markers. CONCLUSIONS: HLA-DQ2 expression and increased intestinal cd-associated antibodies are markers that can identify latent/potential cd in a subgroup of IBS patients who consequently appear to profit from a gluten-free diet.     

Natural Antibiotic Expression in Celiac Disease—Correlation with Villous Atrophy and Response to a Gluten-Free Diet

As infection influences the pathogenesis and presentation of celiac disease, we investigated the expression of natural antibiotics in this condition. Twenty-three adults were prospectively studied: 10 controls and 13 subjects with untreated celiac disease. Distal duodenal biopsies were taken at baseline and after 6 months of a gluten-free diet and assessed for the expression of natural antibiotics. Epithelial human -defensin 1 in subjects with celiac disease had a median of 0.02 unit at baseline, compared with 0.34 unit in controls (P < 0.001). It correlated negatively with the degree of villous atrophy (r = –0.64, P = 0.019) and rose to 0.04 unit on the gluten-free diet (P = 0.035 vs. baseline, P < 0.001 vs. controls). The expression of other antibiotics was unchanged. The expression of epithelial natural antibiotics is limited in celiac disease.     

Immunohistochemical analysis of ZO-1 in the duodenal mucosa of patients with untreated and treated celiac disease

BACKGROUND/AIM: ZO-1 is a good marker for tight junction integrity which may be damaged in many intestinal diseases. ZO-1 can also accumulate in the cellular nucleus in addition to sites of cell-cell contact, suggesting a potential role in cellular proliferation and differentiation. We evaluated the expression and distribution of ZO-1 in patients with celiac disease before and after a gluten-free diet. METHODS: The ZO-1 expression was evaluated semiquantitatively by means of immunohistochemical analysis in duodenal bioptic specimens of 10 consecutive patients with celiac disease before and after a gluten-free diet and in 10 controls. Furthermore, the nuclear staining was analyzed quantitatively, evaluating 3,000 cells for each count, and it was expressed as a percentage of labeled nuclei over the total of analyzed cells. RESULTS: The intestinal mucosa of untreated celiac disease patients shows a globally lower ZO-1 labeling than that of controls. The expression of ZO-1 in the treated celiac mucosa did not differ significantly from normal intestinal mucosa of healthy subjects. At the crypt level of untreated celiac mucosa, a low intensity of nuclear labeling (1.75 +/- 0.32%) was found, while in both treated celiac disease patients and in normal subjects we observed a statistically significant higher percentage of strongly labeled nuclei (53.72 +/- 6.30% and 56.79 +/- 5.45%, respectively; p = 0.0002). CONCLUSIONS: Our data show a global underexpression of ZO-1 in the duodenal mucosa of active celiac disease patients. Gluten withdrawal allows a normalization of the ZO-1 expression in treated celiac disease patients. Furthermore, the particular pattern of ZO-1 resembles the cellular distribution in undifferentiated cells and may be the result of immaturity of the enterocytes in untreated celiac sprue.     

Free perforation of the small intestine in collagenous sprue

A 67-year-old man with celiac disease developed recurrent diarrhea, profound weakness and weight loss, with evidence of marked protein depletion. His clinical course was refractory to a strict gluten-free diet and steroid therapy. Postmortem studies led to definition of unrecognized collagenous sprue that caused ulceration and small intestinal perforation. Although PCR showed identical monoclonal T-cell populations in antemortem duodenal biopsies and postmortem jejunum, careful pathological evaluation demonstrated no frank lymphoma. Rarely, overt or even cryptic T-cell lymphoma may complicate collagenous sprue, however, small intestinal ulcers and perforation may also develop independently. The dramatic findings here may reflect an underlying or early molecular event in the eventual clinical appearance of overt T-cell lymphoma.     

Effect of elemental diet on mucosal immunopathology and clinical symptoms in type 1 refractory celiac disease.

BACKGROUND & AIMS: Patients with celiac disease (CD) who do not improve or exhibit villous atrophy on a gluten-free diet may have type 1 refractory CD (RCD) with a polyclonal mucosal T-cell infiltrate, or type 2 RCD with a monoclonal infiltrate, also termed cryptic T-cell lymphoma. Both conditions are difficult to treat. Here we describe the effects of a nonimmunogenic elemental diet on clinical symptoms and mucosal immunopathology in type 1 RCD. METHODS: Ten CD patients on a strict gluten-free diet were diagnosed with type 1 RCD after extensive clinical evaluation in a tertiary referral hospital. A 4-week amino-acid-based liquid elemental diet regimen was given with no other treatment, except in 1 patient who also received methotrexate. Duodenal biopsy specimens were obtained before and after treatment for histologic assessment, immunophenotyping of intraepithelial lymphocytes, T-cell receptor clonality, mucosal interleukin (IL)-15 expression, flow-cytometric analysis of interferon (IFN)-gamma-secreting T cells, and whole biopsy specimen IFN-gamma messenger RNA determination. RESULTS: Nine patients completed the treatment; however, 1 patient did not tolerate the diet. Histologic improvement and reduced epithelial IL-15 were seen in 8 patients, whereas IFN-gamma-secreting mucosal T cells and IFN-gamma messenger RNA levels decreased in 4 and 7 patients, respectively. Clinical improvement was noted in 6 patients, with 1 patient showing normalization of hypoalbuminemia. Three patients could discontinue their total parenteral nutrition. CONCLUSIONS: Persistent mucosal IFN-gamma and IL-15 production often occurs in type 1 RCD despite conventional treatment. Elemental diet is a therapeutic option that can provide long-term immunopathologic and clinical improvement of this difficult condition.     

Small intestinal permeability as an indicator of jejunal mucosal recovery in patients with celiac sprue on a gluten-free diet

Lactulose/mannitol excretion ratios were measured in 13 patients with celiac disease at diagnosis and after 5-8 months on a gluten-free diet. Jejunal biopsies were assessed histologically at diagnosis and during treatment. The excretion ratios in untreated patients were significantly higher than in 25 normal controls (P less than 0.01). On the diet, the excretion ratios fell in every patient, but in only eight did the ratio return to normal. There was a good correlation between the ratio and jejunal histological grading. During treatment, the ratios significantly inversely correlated with jejunal villous height/mucosal thickness ratios (P less than 0.001). Therefore, excretion ratios provide a well-tolerated noninvasive means of assessing the jejunal mucosa in patients with celiac disease on a gluten-free diet.