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A 2-year follow-up study in children with positive coeliac disease-specific serum antibodies and architecturally normal small intestinal mucosa
Abstracts / Digestive and Liver Disease 38 (2006) A87–A120 PA 10 A 2-YEAR FOLLOW-UP STUDY IN CHILDREN WITH POSITIVE COELIAC DISEASE-SPECIFIC SERUM ANTIBODIES AND ARCHITECTURALLY NORMAL SMALL INTESTINAL MUCOSA V.M. Salvati a,b , A. Tosco a , G. D’Adamo b , A. Sannino a , T. Passaro b , M. Borrelli a , A. Coruzzo a , F. Paparo a , M. Boffardi b , L. Cacace c , R. Auricchio a , L. Greco a , B. Malamisura a,b , R. Troncone a a
Department of Pediatrics and ELFID, University Federico II, Naples, Italy Pediatric Unit Cava de’ Tirreni Hospital, Italy c Institute of Pathology Scafati Hospital, Italy b
Background and aim. In recent years the presence of antiendomysium (EMA) and anti tissue transglutaminase 2 (anti-TG2) with a normal duodenal mucosa has been defined as potential coeliac disease (CD). Aim of our study was to characterise the natural history of potential CD. Patients. Two cohorts of children were recruited: 30 in the Pediatric Unit of Cava de’ Tirreni Hospital and 32 in the Department of Pediatrics at the University Federico II in Naples. Forty-two patients were Marsh T0 and 20 T1. In all serum anti-TG2 and/or EMA were positive. All carried HLA DQ2 and/or DQ8. The mean age was 6.7 years (range: 1.6–14.6). Methods. Growth and nutritional parameters, serology, autoimmunity, faecal calprotectin and intestinal permeability were assessed every 6 months. Patients with persistent EMA and/or anti-TG2 even if not symptomatic were re-biopsied after 2 years. Results. The incidence of potential CD was 9.5–12%. Eight patients were symptomatic and began a gluten-free diet. Symptoms resolved in 3/8 patients. All other patients had a normal daily gluten intake.13/62 potential CD patients were first-degree relatives, 12/62 were affected by autoimmune diseases and 3/62 were asymptomatic. In all other cases gastrointestinal complaints resolved with appropriate medical therapy. 33/54 patients entered the follow-up. After 2 years 17/33 patients were serologically negative, but two developed autoimmune disorders (diabetes, thyroiditis). During the follow-up biopsies were taken from 7 patients all EMA and/or anti-TG2 positive. In 4 patients the second biopsy after 2 years and in one patient the third biopsy after 5 years was still normal. Two patients developed partial villous atrophy, one at the second biopsy after 2 years and another at the third biopsy after 5 years. Clinical and nutritional evaluation was normal in all patients except in one of the two patients who developed villous atrophy. In 9 patients we correlated faecal calprotectin, intestinal permeability and serology. Faecal calprotectin and intestinal permeability were significantly correlated (R = 0.71). Interestingly, in patients with positive EMA and anti-TG2 >10 UA/ml (nv < 5) intestinal permeability and faecal calprotectin were abnormal; furthermore, these patients remained serologically positive during the follow-up and one developed partial villous atrophy. In patients with negative EMA and anti-TG2 < 10 intestinal permeability and faecal calprotectin were normal; during the follow-up they remained serologically negative. Conclusions. Incidence of potential CD is increasing in the last years (3.8–17%). This condition is mainly seen in first-degree relatives (20%) and patients with autoimmune disorders (19%). In our cohort EMA and anti-TG2 returned to normal in 50% of cases, but 6% developed other autoimmune diseases. Duodenal mucosa can remain normal for several years despite the presence of serum EMA and anti-TG2. Finally, the presence of both EMA and anti-TG2 in addition to abnormal intestinal permeability, clinical symptoms and faecal calprotectin seems to be strongly predictive of the evolution to overt coeliac disease. doi:10.1016/j.dld.2006.07.075
A111
PA 11 HLA-DQB1*02 DOSE INFLUENCES RIA ANTI-TISSUE TRANSGLUTAMINASE AUTOANTIBODIES LEVELS AT CD DIAGNOSIS R. Nenna, C. Tiberti, M. Ferri, E. Thanasi, R.P.L. Luparia, A. Castronovo, C. Perricone, B. Mora, M.C. Mazzilli, M. Bonamico Universit`a di Roma “La Sapienza”, Dipartimento di Pediatria, Rome, Italy Aim. Coeliac disease (CD) is a chronic, autoimmune enteropathy caused by the ingestion of gluten and related prolamins, characterised by villous atrophy and crypts’ hyperplasia of small bowel mucosa. CD susceptibility has been shown to be strongly associated with the HLA-DQA1*0501 and -DQB1*0201 alleles, but in several studies the risk of CD has been found significantly grater in subjects omozygous for DQB1*02 allele. RIA antitissue transglutaminase autoantibodies (tTGAb) detection gives supports in identification of candidates to intestinal biopsy, while tTG has proved to play a crucial role in CD aetiopathogenesis. The aim of our study was to investigate whether specific DQB1 alleles could influence tTGAb levels at CD diagnosis. Methods. One hundred and twenty-eight subjects (49 males, 12–541 months, median age 81 months), diagnosed to be affected by coeliac disease according to the revised ESPGHAN criteria, were enrolled in the study. All patients were typed for HLA-DRB1, -DQA1 and -DQB1 genes by PCRSSP using commercially kits, and divided into three groups according to the presence of DQB1*02 allele, as follows: Group 1 = DQB1*02 homozygous; Group 2 = DQB1*02 heterozygous; Group 3 = DQB1*02 negative. All subjects were previously tested for serum IgA presence, and no patients with IgA deficiency participated to the study. Serum samples, at the time of the diagnosis, were collected from all the subjects. IgA-tTG presence was detected through a fluid-phase radioimmunoprecipitation method, using in vitro transcribed and translated 35S-tTG. Results were expressed as a tTG serum index. Results. Hundred percent (26/26), 98.9% (87/88) and 92.9% (13/14) of Group 1, 2 and 3 CD patients were tTGAb positive, respectively. Mean tTGAb index was 0.96 ± 0.49 in Group 1 subjects, 0.73 ± 0.36 in Group 2 and 0.58 ± 0.37 in Group 3. Mean tTGAb indexes were significantly higher in Group 1 with respect to Group 2 (p < 0.01) and Group 3 (p < 0.01) coeliac patients. Conclusions. The study demonstrates, for the first time, on a large series of CD patients, that tTGAb levels are HLA-DQB1*02 dose-dependent, with significantly higher levels in homozygous subjects. This observation confirms our previous results according to which HLA antigens influence CD related AGA production. It is possible that the dose of DQB1*02 allele contributes to modify the cleft of the HLA DQ molecule, thus influencing the antigen affinity and consequently the magnitude of tTGAb production. doi:10.1016/j.dld.2006.07.076 PA 12 ROLE OF WIRELESS CAPSULE ENDOSCOPY IN NON INVASIVE DIAGNOSIS OF SMALL BOWEL DISEASES: A PAEDIATRIC EXPERIENCE F. Torroni a,b , A. Pane a,b , P. De Angelis a,b , T. Caldaro a,b , G. Federici a,b , L. Dall’Oglio a,b a
SC Chirurgia ed Endoscopia Digestiva, Ospedale Pediatrico Bambino Ges`u, Rome, Italy b SC Chirugia ed Endoscopia Digestiva, Rome, Italy Background. Wireless capsule endoscopy (WCE) is a growing up technique, useful in differential diagnosis of many congenital, inflammatory, neoplastic and haemorrhagic pathologies of small bowel, with a positive diagnosis rate of 45–70%. Its role appears to be superior to conventional radiology in detecting minimal change pathologies of small bowel diseases. Aim. To evaluate efficacy of WCE in diagnosis of most small bowel paediatric diseases.
Department of Pediatrics and ELFID, University Federico II, Naples, Italy Pediatric Unit Cava de’ Tirreni Hospital, Italy c Institute of Pathology Scafati Hospital, Italy b
Background and aim. In recent years the presence of antiendomysium (EMA) and anti tissue transglutaminase 2 (anti-TG2) with a normal duodenal mucosa has been defined as potential coeliac disease (CD). Aim of our study was to characterise the natural history of potential CD. Patients. Two cohorts of children were recruited: 30 in the Pediatric Unit of Cava de’ Tirreni Hospital and 32 in the Department of Pediatrics at the University Federico II in Naples. Forty-two patients were Marsh T0 and 20 T1. In all serum anti-TG2 and/or EMA were positive. All carried HLA DQ2 and/or DQ8. The mean age was 6.7 years (range: 1.6–14.6). Methods. Growth and nutritional parameters, serology, autoimmunity, faecal calprotectin and intestinal permeability were assessed every 6 months. Patients with persistent EMA and/or anti-TG2 even if not symptomatic were re-biopsied after 2 years. Results. The incidence of potential CD was 9.5–12%. Eight patients were symptomatic and began a gluten-free diet. Symptoms resolved in 3/8 patients. All other patients had a normal daily gluten intake.13/62 potential CD patients were first-degree relatives, 12/62 were affected by autoimmune diseases and 3/62 were asymptomatic. In all other cases gastrointestinal complaints resolved with appropriate medical therapy. 33/54 patients entered the follow-up. After 2 years 17/33 patients were serologically negative, but two developed autoimmune disorders (diabetes, thyroiditis). During the follow-up biopsies were taken from 7 patients all EMA and/or anti-TG2 positive. In 4 patients the second biopsy after 2 years and in one patient the third biopsy after 5 years was still normal. Two patients developed partial villous atrophy, one at the second biopsy after 2 years and another at the third biopsy after 5 years. Clinical and nutritional evaluation was normal in all patients except in one of the two patients who developed villous atrophy. In 9 patients we correlated faecal calprotectin, intestinal permeability and serology. Faecal calprotectin and intestinal permeability were significantly correlated (R = 0.71). Interestingly, in patients with positive EMA and anti-TG2 >10 UA/ml (nv < 5) intestinal permeability and faecal calprotectin were abnormal; furthermore, these patients remained serologically positive during the follow-up and one developed partial villous atrophy. In patients with negative EMA and anti-TG2 < 10 intestinal permeability and faecal calprotectin were normal; during the follow-up they remained serologically negative. Conclusions. Incidence of potential CD is increasing in the last years (3.8–17%). This condition is mainly seen in first-degree relatives (20%) and patients with autoimmune disorders (19%). In our cohort EMA and anti-TG2 returned to normal in 50% of cases, but 6% developed other autoimmune diseases. Duodenal mucosa can remain normal for several years despite the presence of serum EMA and anti-TG2. Finally, the presence of both EMA and anti-TG2 in addition to abnormal intestinal permeability, clinical symptoms and faecal calprotectin seems to be strongly predictive of the evolution to overt coeliac disease. doi:10.1016/j.dld.2006.07.075
A111
PA 11 HLA-DQB1*02 DOSE INFLUENCES RIA ANTI-TISSUE TRANSGLUTAMINASE AUTOANTIBODIES LEVELS AT CD DIAGNOSIS R. Nenna, C. Tiberti, M. Ferri, E. Thanasi, R.P.L. Luparia, A. Castronovo, C. Perricone, B. Mora, M.C. Mazzilli, M. Bonamico Universit`a di Roma “La Sapienza”, Dipartimento di Pediatria, Rome, Italy Aim. Coeliac disease (CD) is a chronic, autoimmune enteropathy caused by the ingestion of gluten and related prolamins, characterised by villous atrophy and crypts’ hyperplasia of small bowel mucosa. CD susceptibility has been shown to be strongly associated with the HLA-DQA1*0501 and -DQB1*0201 alleles, but in several studies the risk of CD has been found significantly grater in subjects omozygous for DQB1*02 allele. RIA antitissue transglutaminase autoantibodies (tTGAb) detection gives supports in identification of candidates to intestinal biopsy, while tTG has proved to play a crucial role in CD aetiopathogenesis. The aim of our study was to investigate whether specific DQB1 alleles could influence tTGAb levels at CD diagnosis. Methods. One hundred and twenty-eight subjects (49 males, 12–541 months, median age 81 months), diagnosed to be affected by coeliac disease according to the revised ESPGHAN criteria, were enrolled in the study. All patients were typed for HLA-DRB1, -DQA1 and -DQB1 genes by PCRSSP using commercially kits, and divided into three groups according to the presence of DQB1*02 allele, as follows: Group 1 = DQB1*02 homozygous; Group 2 = DQB1*02 heterozygous; Group 3 = DQB1*02 negative. All subjects were previously tested for serum IgA presence, and no patients with IgA deficiency participated to the study. Serum samples, at the time of the diagnosis, were collected from all the subjects. IgA-tTG presence was detected through a fluid-phase radioimmunoprecipitation method, using in vitro transcribed and translated 35S-tTG. Results were expressed as a tTG serum index. Results. Hundred percent (26/26), 98.9% (87/88) and 92.9% (13/14) of Group 1, 2 and 3 CD patients were tTGAb positive, respectively. Mean tTGAb index was 0.96 ± 0.49 in Group 1 subjects, 0.73 ± 0.36 in Group 2 and 0.58 ± 0.37 in Group 3. Mean tTGAb indexes were significantly higher in Group 1 with respect to Group 2 (p < 0.01) and Group 3 (p < 0.01) coeliac patients. Conclusions. The study demonstrates, for the first time, on a large series of CD patients, that tTGAb levels are HLA-DQB1*02 dose-dependent, with significantly higher levels in homozygous subjects. This observation confirms our previous results according to which HLA antigens influence CD related AGA production. It is possible that the dose of DQB1*02 allele contributes to modify the cleft of the HLA DQ molecule, thus influencing the antigen affinity and consequently the magnitude of tTGAb production. doi:10.1016/j.dld.2006.07.076 PA 12 ROLE OF WIRELESS CAPSULE ENDOSCOPY IN NON INVASIVE DIAGNOSIS OF SMALL BOWEL DISEASES: A PAEDIATRIC EXPERIENCE F. Torroni a,b , A. Pane a,b , P. De Angelis a,b , T. Caldaro a,b , G. Federici a,b , L. Dall’Oglio a,b a
SC Chirurgia ed Endoscopia Digestiva, Ospedale Pediatrico Bambino Ges`u, Rome, Italy b SC Chirugia ed Endoscopia Digestiva, Rome, Italy Background. Wireless capsule endoscopy (WCE) is a growing up technique, useful in differential diagnosis of many congenital, inflammatory, neoplastic and haemorrhagic pathologies of small bowel, with a positive diagnosis rate of 45–70%. Its role appears to be superior to conventional radiology in detecting minimal change pathologies of small bowel diseases. Aim. To evaluate efficacy of WCE in diagnosis of most small bowel paediatric diseases.