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Lamina propria (LPL) and intraepithelial lymphocyte (IEL) apoptosis in coeliac disease-associated T-cell lymphoma
Small Bowel
109 BARRIER LOSS AND ULTRASTRUCTURAL CHANGES OF SMALL BOWEL MUCOSA IN TYPE 1 DIABETES MELLITUS (DMI) Semndolfo M, ItisCO D ($), deMagistris L, SaponeA, Fiaodm P.+Belletta M, Car&d M (*), GenerosoM (*), Defois D (+). Esposito V (+), Prism F ($), Cd R. Diptimel~to di Pediehia(S), Cottedradi Gastroeotnologi~ Istitoto di Farmapologia(*), Istitoto di Amtomia (+), SUN, Napoli SUN Aim of this work was to investigateIntestinal Permeability(IP) in type 1 DiabetesMellitos, in patimts both with anew diagoosis(neoDM1) andwith a diseesehistory longer than 12 months @Ml), all being in good fooctionel conditions.No patientspnscnted a concomitant celiec disease. When possible,small intestinalmocosa biopsieswere collected andanalysedby meem of conventionalmicmscopy (CM) andtmosmissionelectmn microscopy (TEM). The IP wes evaluated bv meansofthe LactoloseiMem,itol(IA/MA=mean+SD) with theseresults: a\ 0.044*0.03 io 32 tiMI patients (M=ZO, F=12,15.917.6 years); b) 0.090&l in 15neoDM1 pients (M=5, F=lO, 7.613.01years); c) 0.027+0.06in 25 control subjects(M=lZ, F=l3,27.~8.01 years). LA/MA median valuesof eitherpatients gmup @Ml andneoDMI1) were significantly different from those of controls with ~00001 endp=O.OOOltwpectively (Meoo Whitney test). There wes no differewe betweeothe median LA&IA values in the two gmops ofpatients, with @.607. St&tically significant difference betweenall groups was continned by analysesof variance rnth p
111 Minimal gliadin ingestionin cool& patientscan prevent histological recovery undetectableon eitherclinical or serological ground F Biagi, D Pezzimenti,1Campanella,S Msrtucci, *HJ Ellis, *PI Ciclitwa GR Corazza. Gastmentemlcgy Unit, IRCCS Policlioico SanMatteo, University ofPavia, Italy; Gastmcotemlogy Department,Rayoe Institute, KCL, St.Thomas’Hospitel,London, UK Pobcbmco S.Mattee Introduction: In the last few years sane authoritiessuanestedthateefieots affected bv coeliec disease(CD) can be edequat~lyfollowed up on the b& of only citic.4 and serologicalresponseto a gluten-freediet (GFD). Thus, a cnntml duodenalbiopsy would not beeo oecessay any longer. We repal here thecases of two CD patientswhich do not-&low us to support this sb&gy~Cc&l: in 1998a 41.year-old women was found to bea&?&d by CD in anotherhospital. She was suffering fmm diarrhoea,weixht loss. eoaemia.abdominaloaio andHesbimoto’s thvmiditis. Small bowel mucosawas flat andendomysial antibodies(Eh@ were positive. She c&mewed a GFD. When we saw her in May 2001,symptoms had disappeared,EM4 were negstive and only TTA were border line. However, multiple duodenalbiopsiesdemonstrateda tlat mucosa. Although she thought shewas very careful with ha diet, an interview showed that her job forced her to eatin restaurantsat leastonce a week. We have some evidencethat that nw, cewe inadvertent eluten intake.Case1: a 32-year-old religious women was admittedto w&r hospital in Augesr1998. She was complaining of diurboee, weight loss, snd imndeficiency aoaemia.A flat small bowel mwxa andpositive EMA proved that she was at&ted by CD. A GFD wa8introduced We saw her in December 1999.Diarrhoee hadstoppedandweight loss hadhem recovered. However, shewas alI anemic andEMA were positive. An interview revealedthat shewas not on a strict GFD, and, although we explainedher how to follow a strict GFD, she refused to stop taking a daily commonionwafer. Seventeenmonths leter, multiple duo&ne.l biopsiesshowedpersistence of severe villous ahophy. Nevertheless, shewes well, aoaemiahad disappeared,and coeliec antibodies were not positive. Apart from the daily intie of a small 6agnxnt of communion wafer, sheWBSon a strict GFD, that WBSchecked through a dietary diary. The &gnents of wafer weigh approximately 30 mg eachandwe measuredthat contain 0.5 mg of gliadin. Conclusions: thesetwo cases confirm that minimal gluten ingestioncan prevent histological recovery. Moreover, this canot be detectedon either a clinical or a serological gmood.A control intestinalbiopsy is msndatay to evaluatethe histologicalresponseto a GFD, the factor pmtecting from severe complications
110 LAMlNA PROPRIA (LPL) AND INTRABPITHELIAL LYMPHOCYTE (IEL) APOPTOSIS IN COELIAC DISEASE-ASSOCIATED T-CELL LYMPHOMA Di SebetiooA, Cicwcioppo R, D’AId S, Ricevuti L, Boovicbd F, Cifone MG, Corazza GR. Gashocntemlogy Unit, IRCCS Poticlioico S. Metteo,University of Pavie,Depts of b&met and ExperimeotelMedicine, University of L’Aqoila, Dept of Internal Medicine, University of Bologna, Italy.
NUCLEAR FLUORESCENCE REACTIVITY: A NOVEL SENSITIVE MARKER IN THE flNE FOLLOW-UP OF CELlAC MSEASE PATIENTS.
Pobcliaiw S.Metteo Backgmond & Aims: To test the hypothesis that defective mucosalT-lymphocyte apoptosisis involved in the oathonenesisof eotemoethv-associatedT-cell lvmoboma in coeliac disease(CD), we iovestigated’LPL-nd IEL epoptosis &I expression of B&i, k mtiapoptotic protein, id CD patientscomplicatedwith intestinalT-cell lymphoma (ITL). Patients&Methods: Endosmpic biopsy specimenswere obtainedfmm the secondpart of duodenumof 8 CD patientscomplicated with ITL, 10 on&e&d and 10 @eat&oocomplicatedCD petieots, and 10coosenting subjects undergoingopper ges!mintestinalendoscopy for tboctiooel dyspepsia Apoptosis detectionwas sssessedby TUNSL technique(Apoptag kis Gncor). B&Z expressionwas evaluatedby immonobistochemistry with themoose mono&al anti-humanB&Z antibody (DAKO). To determinewhetherTUNBL+ andB&2+ cells were T-lymphocytes, seriatesections were incubated with apolyclonal anti-CD3 antibody (DAKO). Resolts: lo complicatedCD the paceotage of TUNEL+ LPLs (mean 0.8%) wes significantly lower thaoin controls (mea 2.4%, p
Background Celiac disease (CD) is defined as a permanent intolerance of the small intestine to gluten. Nowadays there is no way to verify the real wmpliance to a gluten free diet (GFD) in CD patients during treatment and/or the presence of slight dietary transgressions. It has been recently shorn a cmss-readivity between wheat proteins and a 56KDa nuclear autoantigen. Moreover. an a previous wfk we have already described a nuclear fluorercena, on smwth muscle of monkey esophagus, in CD patients in remission, of as yet unknown significance. Aim of this work is to characterize this nuclear fluorescence reactivity (NFR) and to study the possibility of using it in the fine follow-up of treated CD patients as well as its possible relationship with dietary trangressions. MWsrials and Methods Group 1’ 20 newly diagnosed CD pts (7MJ13F. mean age 22.3 y. range 16-46 y) with villous abophy and sera EMA positive. These pabents underwent a GFD and were followed for 6-12 mo. Group 2: 87 treated CD pts (31hU56F,mean age 31.3 y, range 1854 y), after at least 12 mo of GFD. NFR kinetic has been studied in these pts. both EMA and NFR negative. EMA I@ were detected in all pts. Results All 20 CD pts of group 1 showed, m 76k.34 days of a correct GFD, the disappearance of EMA when EMA disappeared a NFR was observed I” all these pts. NFR completely disappeared in further 75Ml days of GFD. Among the pts belonging to group 2. 24 pts ware found NFR positive but EMA negative at a cartam point of the follow-up. A careful anamnestic evaluation allowed to demonstrate that these pts introduced small amounts of gluten in their diet; 10 out of these pts continued to introduce small amounts of gluten and in 1-2 mo became serum EMA positive. On the other hand. the remaining 14 patients, who started again a strict GFD, showed NFR disappearance in further two months of diet Conclusion In th!s work we showed EMA disappearanca in 76i.34 days of stwt GFD. wth NFR appwanca and persistence for further 75Ml days. The two d&rent patterns .are never co&pressed suggesting that NFR has different appearance time than EMA and furthermore, the possibility to use NFR as a marker I” the fine follow-up of CD pts. Mareover. &er re-intmduction of small amounts of gluten into the diet, EMA persisted negative for a long time while NFR appears in few days NFR are, therefore. more sensitive than EMA as early marker of reactivation and could be a useful marker of the comphance to GFD In cond~eion in this studv we showed that NFR is due to B novel antibodv which presents a strong glut&dependency and that, therefore, could be 4 novel useful marker in the fine follow-up of CD pts.
A66
L Sabbatella, M. Dt Tola, T. Dt Cello, 5. Vetraw, H.F. Palumbo, C. Maffta, C. Plcchi, 8%. Anania and A Plcaretti Department of Clinical Sciences. University ‘La Sapienza’, Rome, Italy.
109 BARRIER LOSS AND ULTRASTRUCTURAL CHANGES OF SMALL BOWEL MUCOSA IN TYPE 1 DIABETES MELLITUS (DMI) Semndolfo M, ItisCO D ($), deMagistris L, SaponeA, Fiaodm P.+Belletta M, Car&d M (*), GenerosoM (*), Defois D (+). Esposito V (+), Prism F ($), Cd R. Diptimel~to di Pediehia(S), Cottedradi Gastroeotnologi~ Istitoto di Farmapologia(*), Istitoto di Amtomia (+), SUN, Napoli SUN Aim of this work was to investigateIntestinal Permeability(IP) in type 1 DiabetesMellitos, in patimts both with anew diagoosis(neoDM1) andwith a diseesehistory longer than 12 months @Ml), all being in good fooctionel conditions.No patientspnscnted a concomitant celiec disease. When possible,small intestinalmocosa biopsieswere collected andanalysedby meem of conventionalmicmscopy (CM) andtmosmissionelectmn microscopy (TEM). The IP wes evaluated bv meansofthe LactoloseiMem,itol(IA/MA=mean+SD) with theseresults: a\ 0.044*0.03 io 32 tiMI patients (M=ZO, F=12,15.917.6 years); b) 0.090&l in 15neoDM1 pients (M=5, F=lO, 7.613.01years); c) 0.027+0.06in 25 control subjects(M=lZ, F=l3,27.~8.01 years). LA/MA median valuesof eitherpatients gmup @Ml andneoDMI1) were significantly different from those of controls with ~00001 endp=O.OOOltwpectively (Meoo Whitney test). There wes no differewe betweeothe median LA&IA values in the two gmops ofpatients, with @.607. St&tically significant difference betweenall groups was continned by analysesof variance rnth p
111 Minimal gliadin ingestionin cool& patientscan prevent histological recovery undetectableon eitherclinical or serological ground F Biagi, D Pezzimenti,1Campanella,S Msrtucci, *HJ Ellis, *PI Ciclitwa GR Corazza. Gastmentemlcgy Unit, IRCCS Policlioico SanMatteo, University ofPavia, Italy; Gastmcotemlogy Department,Rayoe Institute, KCL, St.Thomas’Hospitel,London, UK Pobcbmco S.Mattee Introduction: In the last few years sane authoritiessuanestedthateefieots affected bv coeliec disease(CD) can be edequat~lyfollowed up on the b& of only citic.4 and serologicalresponseto a gluten-freediet (GFD). Thus, a cnntml duodenalbiopsy would not beeo oecessay any longer. We repal here thecases of two CD patientswhich do not-&low us to support this sb&gy~Cc&l: in 1998a 41.year-old women was found to bea&?&d by CD in anotherhospital. She was suffering fmm diarrhoea,weixht loss. eoaemia.abdominaloaio andHesbimoto’s thvmiditis. Small bowel mucosawas flat andendomysial antibodies(Eh@ were positive. She c&mewed a GFD. When we saw her in May 2001,symptoms had disappeared,EM4 were negstive and only TTA were border line. However, multiple duodenalbiopsiesdemonstrateda tlat mucosa. Although she thought shewas very careful with ha diet, an interview showed that her job forced her to eatin restaurantsat leastonce a week. We have some evidencethat that nw, cewe inadvertent eluten intake.Case1: a 32-year-old religious women was admittedto w&r hospital in Augesr1998. She was complaining of diurboee, weight loss, snd imndeficiency aoaemia.A flat small bowel mwxa andpositive EMA proved that she was at&ted by CD. A GFD wa8introduced We saw her in December 1999.Diarrhoee hadstoppedandweight loss hadhem recovered. However, shewas alI anemic andEMA were positive. An interview revealedthat shewas not on a strict GFD, and, although we explainedher how to follow a strict GFD, she refused to stop taking a daily commonionwafer. Seventeenmonths leter, multiple duo&ne.l biopsiesshowedpersistence of severe villous ahophy. Nevertheless, shewes well, aoaemiahad disappeared,and coeliec antibodies were not positive. Apart from the daily intie of a small 6agnxnt of communion wafer, sheWBSon a strict GFD, that WBSchecked through a dietary diary. The &gnents of wafer weigh approximately 30 mg eachandwe measuredthat contain 0.5 mg of gliadin. Conclusions: thesetwo cases confirm that minimal gluten ingestioncan prevent histological recovery. Moreover, this canot be detectedon either a clinical or a serological gmood.A control intestinalbiopsy is msndatay to evaluatethe histologicalresponseto a GFD, the factor pmtecting from severe complications
110 LAMlNA PROPRIA (LPL) AND INTRABPITHELIAL LYMPHOCYTE (IEL) APOPTOSIS IN COELIAC DISEASE-ASSOCIATED T-CELL LYMPHOMA Di SebetiooA, Cicwcioppo R, D’AId S, Ricevuti L, Boovicbd F, Cifone MG, Corazza GR. Gashocntemlogy Unit, IRCCS Poticlioico S. Metteo,University of Pavie,Depts of b&met and ExperimeotelMedicine, University of L’Aqoila, Dept of Internal Medicine, University of Bologna, Italy.
NUCLEAR FLUORESCENCE REACTIVITY: A NOVEL SENSITIVE MARKER IN THE flNE FOLLOW-UP OF CELlAC MSEASE PATIENTS.
Pobcliaiw S.Metteo Backgmond & Aims: To test the hypothesis that defective mucosalT-lymphocyte apoptosisis involved in the oathonenesisof eotemoethv-associatedT-cell lvmoboma in coeliac disease(CD), we iovestigated’LPL-nd IEL epoptosis &I expression of B&i, k mtiapoptotic protein, id CD patientscomplicatedwith intestinalT-cell lymphoma (ITL). Patients&Methods: Endosmpic biopsy specimenswere obtainedfmm the secondpart of duodenumof 8 CD patientscomplicated with ITL, 10 on&e&d and 10 @eat&oocomplicatedCD petieots, and 10coosenting subjects undergoingopper ges!mintestinalendoscopy for tboctiooel dyspepsia Apoptosis detectionwas sssessedby TUNSL technique(Apoptag kis Gncor). B&Z expressionwas evaluatedby immonobistochemistry with themoose mono&al anti-humanB&Z antibody (DAKO). To determinewhetherTUNBL+ andB&2+ cells were T-lymphocytes, seriatesections were incubated with apolyclonal anti-CD3 antibody (DAKO). Resolts: lo complicatedCD the paceotage of TUNEL+ LPLs (mean 0.8%) wes significantly lower thaoin controls (mea 2.4%, p
Background Celiac disease (CD) is defined as a permanent intolerance of the small intestine to gluten. Nowadays there is no way to verify the real wmpliance to a gluten free diet (GFD) in CD patients during treatment and/or the presence of slight dietary transgressions. It has been recently shorn a cmss-readivity between wheat proteins and a 56KDa nuclear autoantigen. Moreover. an a previous wfk we have already described a nuclear fluorercena, on smwth muscle of monkey esophagus, in CD patients in remission, of as yet unknown significance. Aim of this work is to characterize this nuclear fluorescence reactivity (NFR) and to study the possibility of using it in the fine follow-up of treated CD patients as well as its possible relationship with dietary trangressions. MWsrials and Methods Group 1’ 20 newly diagnosed CD pts (7MJ13F. mean age 22.3 y. range 16-46 y) with villous abophy and sera EMA positive. These pabents underwent a GFD and were followed for 6-12 mo. Group 2: 87 treated CD pts (31hU56F,mean age 31.3 y, range 1854 y), after at least 12 mo of GFD. NFR kinetic has been studied in these pts. both EMA and NFR negative. EMA I@ were detected in all pts. Results All 20 CD pts of group 1 showed, m 76k.34 days of a correct GFD, the disappearance of EMA when EMA disappeared a NFR was observed I” all these pts. NFR completely disappeared in further 75Ml days of GFD. Among the pts belonging to group 2. 24 pts ware found NFR positive but EMA negative at a cartam point of the follow-up. A careful anamnestic evaluation allowed to demonstrate that these pts introduced small amounts of gluten in their diet; 10 out of these pts continued to introduce small amounts of gluten and in 1-2 mo became serum EMA positive. On the other hand. the remaining 14 patients, who started again a strict GFD, showed NFR disappearance in further two months of diet Conclusion In th!s work we showed EMA disappearanca in 76i.34 days of stwt GFD. wth NFR appwanca and persistence for further 75Ml days. The two d&rent patterns .are never co&pressed suggesting that NFR has different appearance time than EMA and furthermore, the possibility to use NFR as a marker I” the fine follow-up of CD pts. Mareover. &er re-intmduction of small amounts of gluten into the diet, EMA persisted negative for a long time while NFR appears in few days NFR are, therefore. more sensitive than EMA as early marker of reactivation and could be a useful marker of the comphance to GFD In cond~eion in this studv we showed that NFR is due to B novel antibodv which presents a strong glut&dependency and that, therefore, could be 4 novel useful marker in the fine follow-up of CD pts.
A66
L Sabbatella, M. Dt Tola, T. Dt Cello, 5. Vetraw, H.F. Palumbo, C. Maffta, C. Plcchi, 8%. Anania and A Plcaretti Department of Clinical Sciences. University ‘La Sapienza’, Rome, Italy.