Rebeca Santaolalla

Spectrum of gluten-sensitive enteropathy in first-degree relatives of patients with coeliac disease: clinical relevance of lymphocytic enteritis.

Background: Limited data on a short series of patients suggest that lymphocytic enteritis (classically considered as latent coeliac disease) may produce symptoms of malabsorption, although the true prevalence of this situation is unknown. Serological markers of coeliac disease are of little diagnostic value in identifying these patients. Aims: To evaluate the usefulness of human leucocyte antigen-DQ2 genotyping followed by duodenal biopsy for the detection of gluten-sensitive enteropathy in first-degree relatives of patients with coeliac disease and to assess the clinical relevance of lymphocytic enteritis diagnosed with this screening strategy. Patients and methods: 221 first-degree relatives of 82 DQ2+ patients with coeliac disease were consecutively included. Duodenal biopsy (for histological examination and tissue transglutaminase antibody assay in culture supernatant) was carried out on all DQ2+ relatives. Clinical features, biochemical parameters and bone mineral density were recorded. Results: 130 relatives (58.8%) were DQ2+, showing the following histological stages: 64 (49.2%) Marsh 0; 32 (24.6%) Marsh I; 1 (0.8%) Marsh II; 13 (10.0%) Marsh III; 15.4% refused the biopsy. 49 relatives showed gluten sensitive enteropathy, 46 with histological abnormalities and 3 with Marsh 0 but positive tissue transglutaminase antibody in culture supernatant. Only 17 of 221 relatives had positive serological markers. Differences in the diagnostic yield between the proposed strategy and serology were significant (22.2% v 7.2%, p<0.001). Relatives with Marsh I and Marsh II–III were more often symptomatic (56.3% and 53.8%, respectively) than relatives with normal mucosa (21.1%; pu200a=u200a0.002). Marsh I relatives had more severe abdominal pain (pu200a=u200a0.006), severe distension (pu200a=u200a0.047) and anaemia (pu200a=u200a0.038) than those with Marsh 0. The prevalence of abnormal bone mineral density was similar in relatives with Marsh I (37%) and Marsh III (44.4%). Conclusions: The high number of symptomatic patients with lymphocytic enteritis (Marsh I) supports the need for a strategy based on human leucocyte antigen-DQ2 genotyping followed by duodenal biopsy in relatives of patients with coeliac disease and modifies the current concept that villous atrophy is required to prescribe a gluten-free diet.

Paucicellular Lymphocytic Colitis : Is It a Minor Form of Lymphocytic Colitis? A Clinical Pathological and Immunological Study

OBJECTIVES:It has been suggested that paucicellular lymphocytic colitis (PLC) should be considered to be part of the morphological spectrum of microscopic colitis. The aim of the study was to evaluate whether PLC may be considered to be a true microscopic colitis, and in this case, whether it is a minor form of lymphocytic colitis (LC) or a different entity.METHODS:All incident cases of PLC, LC, and collagenous colitis (CC) during the period 2004–2006 were included. The incidence rate and the clinical, histopathological, and immunological features of PLC were assessed and compared with those of both LC and CC. Immunoreactivities to CD25, c-Kit, and FOXP3 in lamina propria were assessed.RESULTS:In all, 19 patients with CC, 19 with LC, and 26 with PLC were identified. CD25+FOXP3+ expression was seen only in classical forms of microscopic colitis: 12 of 19 LC, 14 of 20 CC, and none of 20 PLC cases (P<0.0001). Diarrhea ceased in 21 of the 26 patients, with a decrease in the daily stool number from 5.08±0.44 to 1.7±0.2 (P<0.005). The five patients with no response to therapy fulfilled the Rome II criteria of irritable bowel syndrome (IBS).CONCLUSIONS:The incidence rate of PLC, identified using objective histological criteria, was higher than those of CC and LC. The lack of expression of CD25+FOXP3+ cells in PLC, in contrast to those seen in both LC and CC, would suggest the existence of different pathophysiological mechanisms and does not support that PLC is a minor form of LC.

Intestinal spirochetosis and chronic watery diarrhea: Clinical and histological response to treatment and long-term follow up

Background:u2002 The clinical significance of intestinal spirochetosis is uncertain, therefore the aim of the present paper was to assess the prevalence of histological intestinal spirochetosis in patients with and without chronic watery diarrhea and to evaluate its clinical relevance.

The prevalence of coeliac disease is significantly higher in children compared with adults.

Backgroundu2002 Some limited studies of coeliac disease have shown higher frequency of coeliac disease in infancy and adolescence than in adulthood. This finding has remained unnoticed and not adequately demonstrated.

Diagnostic value of duodenal antitissue transglutaminase antibodies in gluten-sensitive enteropathy

Backgroundu2002 In gluten‐sensitive enteropathy, antitissue transglutaminase antibodies are synthesized in the duodenum.

Apoptosis resistance of mucosal lymphocytes and IL-10 deficiency in patients with steroid-refractory Crohn's disease.

Background: Apoptosis resistance of T‐cells is considered an abnormality of immune pathways in Crohns disease (CD). It has been previously shown that corticosteroids induce apoptosis of cells involved in inflammation. Thus, our aim was to assess the apoptosis of mononuclear cells and pro/antiinflammatory cytokines in the intestinal mucosa of patients with active CD, related to steroid response, and identify cellular and molecular factors that may predict this response to therapy. Methods: Patients with CD (n = 26), ulcerative colitis (UC) (n = 32), and controls (n = 10) were prospectively studied with mucosal biopsies before and 7‐10 days after corticosteroid treatment. Immunophenotype and apoptosis of T and B lymphocytes, plasma cells, and macrophages were assessed by flow cytometry, immunohistochemistry, and immunofluorescence. The cytokine expression pattern was evaluated by quantitative polymerase chain reaction (PCR). Results: Apoptosis resistance of T and B lymphocytes was observed only in steroid‐refractory and ‐dependent CD patients as compared to responsive patients (P = 0.032; P = 0.004, respectively), being evident after steroid treatment. Interleukin (IL)‐10 was markedly increased at baseline in steroid‐responsive patients compared to the nonresponders (P = 0.006; sensitivity: 88.8%; specificity: 66.6% to predict steroid response). Conclusions: Apoptosis resistance of mucosal T and B cells in steroid‐refractory and ‐dependent CD patients appears during the evolution of the acute phase, limiting its clinical application as a predictor marker. In contrast, increased expression of IL‐10 at an early stage of active steroid‐sensitive CD patients supports its usefulness at predicting a good steroid response. Steroid‐dependent and ‐refractory CD patients share similar molecular and cellular pathophysiological mechanisms. (Inflamm Bowel Dis 2010;)

Comparison of lymphocyte isolation methods for endoscopic biopsy specimens from the colonic mucosa

An ideal method of immune cell isolation should provide maximum cell yield without disturbing functional properties. Intestinal endoscopic biopsies, in contrast to surgical samples, allow the study of all disease stages but have the drawback of a minimum amount of tissue available, making protocol optimization mandatory. We compared for the first time two methods of separation of colonic epithelium and five methods of lamina propria cell isolation for colonic biopsy specimens (mechanical, enzymatic and organ culture protocols). Lymphocyte number, viability and phenotype (CD45+, CD103+, CD3+, CD4+, CD8+, CD19+, CD16-56+) were analyzed by flow cytometry. Neither of the two epithelial detachment protocols achieved proper epithelial separation, though the high intensity ion chelation method was more accurate. Maximum cell yield of lamina propria lymphocytes without phenotypic modification was obtained with overnight smooth enzymatic digestion. High dose collagenase incubation caused a marked decrease in CD4+ lymphocytes of the lamina propria as compared to low enzymatic method (p=0.004). Mechanical and biopsy culture are not advisable methods because of the low cell yield, and phenotypic alterations and high contamination rate, respectively.