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P.18.4 USE OF AUTOLOGOUS BONE MARROW-DERIVED MESENCHYMAL STROMAL CELL (MSC) TRANSPLANTATION AS RESCUE THERAPY FOR ADULT AUTOIMMUNE ENTEROPATHY
Abstracts of the 18th National Congress of Digestive Diseases / Digestive and Liver Disease 44S (2012) S55–S220 P.18.3 IMMUNE RECONSTITUTION INFLAMMATORY SYNDROME IN ITALIAN PATIENTS WITH WHIPPLE’S DISEASE F. Biagi ∗ ,1 , L. Trotta 1 , D. Balduzzi 1 , A. Marchese 1 , C. Vattiato 1 , P.I. Bianchi 1 , M. Di Stefano 1 , F. Fenollar 2 , G.R. Corazza 1 1 Universita’ di Pavia, Pavia, Italy; 2 Université de Aix-Marseille, Marsiglia, France
Background and aim: Whipple’s disease (WD) is a very rare chronic multisystemic infection caused by Tropheryma whipplei (TW), a Gram-positive actinomycete, which in the majority of cases responds to a prolonged antibiotic treatment. In some patients the start of the treatment is, however, followed by the recurrence of a form of inflammation that does not respond any longer to antimicrobials but responds to steroids. Since polymerase chain reaction is negative for TW, this reinflammation cannot be a relapse of WD itself. Very recently, it has been recognised as a complication of WD and defined immune reconstitution inflammatory syndrome (IRIS). Aims: to study the prevalence and the clinical features of IRIS in WD patients attending our clinic. Material and methods: Between Jan 2000 and Sept 2011, 22 patients (4F, mean age 53.7±11.7 yrs) affected by WD attended our clinic. Evidence of IRIS, according to Feurle et al. [1], were retrospectively revaluated in the clinical notes. Patients with no evidence of IRIS served as controls for the clinical findings. Results: Recurrence of arthralgia (4 pts) and/or fever (2 pts) allowed a diagnosis of IRIS in 5/22 patients (22.7%). One patient died. Previous immunosuppressive therapy was found in 5/5 patients with IRIS but only in 7/17 controls (Fisher test, p=0.039). Both age at diagnosis (58.4±11.9 vs. 52.3±11.7 yrs) and diagnostic delay (6.6±3.5 vs. 4.7±3.5 yrs) were higher in patients with IRIS compared to controls. However, statistically significance was not reached. Probably because of the relatively small sample, clinical features and HLA did not differ between patients and controls. Conclusions: IRIS is a rather frequent complications of WD that must be promptly recognised because its course can be fatal. The risk of IRIS is greatly increased in patients previously treated with immunosuppressive therapy. Prospective studies are required to better define the clinical features of this complication of WD. Reference: [1] Feurle GE et al, Ann Intern Med 2010;153:710-7.
P.18.4 USE OF AUTOLOGOUS BONE MARROW-DERIVED MESENCHYMAL STROMAL CELL (MSC) TRANSPLANTATION AS RESCUE THERAPY FOR ADULT AUTOIMMUNE ENTEROPATHY R. Ciccocioppo ∗ ,1 , M.L. Russo 1 , F. Biagi 1 , M.E. Bernardo 2 , M.A. Avanzini 3 , A. Gallia 1 , V. Boccaccio 1 , V. Imbesi 1 , F. Racca 1 , A. Vanoli 4 , L. Catenacci 3 , F. Locatelli 5 , G.R. Corazza 1 1 Clinica Medica I, Fondazione Irccs Policlinico San Matteo, Università degli Studi di Pavia, Pavia, Italy; 2 Dipartimento di Oncoematologia Pediatrica e Medicina Trasfusionale, Ospedale Bambino Gesù, Roma, Italy; 3 Laboratorio di Immunologia e Trapianti, Oncoematologia Pediatrica, Fondazione Irccs Policlinico San Matteo, Pavia, Italy; 4 Servizio di Anatomia Patologica, Fondazione Irccs Policlinico S. Matteo, Università degli Studi di Pavia, Pavia, Italy; 5 Dipartimento di Oncoematologia Pediatrica e Medicina Trasfusionale, Ospedale Bambino Gesù, Università degli Studi di Pavia, Roma, Pavia, Italy
Background and aim: Adult autoimmune enteropathy (AE) is a rare condition characterized by the presence of anti-enterocyte antibodies (AEA) and small bowel villous atrophy causing severe malabsorption. Its treatment is based on immunosuppressive or biological therapy, with parenteral nutrition reserved to severe cases. MSC, thanks to their regenerative and immunomodulatory function, was successful to treat AE in a mice model of multiorgan autoimmunity due to mutation of Foxp3, a transcriptor factor expressed by regulatory T cells. We used autologous bone-marrow MSC transplantation as rescue therapy in a 61-year old woman with life-threatening malabsorption syndrome due to AE refractory to steroid therapy.
S205
Material and methods: MSC were isolated and expanded ex vivo following standardized protocol. AEA were tested by indirect immunofluorescence. Circulating and mucosal Foxp3+ T cells were detected by flow-cytometry and immunohistochemistry on duodenal biopsies, respectively. Secretory IgA (sIgA) were quantified in saliva samples by electroimmunodiffusion assay. Results: MSC expansion was successful thus allowing 2 systemic infusion of 1,8×106 MSC/pro kg two weeks a part without adverse effects. During the first month after transplantation, the patient experienced wellbeing and regularization of both stool frequency and body weight. At this time, the positivity of AEA was no longer detected and a patchy recovery of duodenal mucosa was evident. After a further month, she had relapse and an additional MSC infusion at the same dose was performed allowing a transient wellness. Total parenteral nutrition and steroid therapy were, therefore, re-established leading to satisfactory clinical conditions and negativity of both serological and histological findings. Remarkably, after each MSC transplantation, a transient mucosal enrichment and peripheral blood depletion of FoxP3+ T cells were observed. The levels of sIgA were found increased upon MSC infusions, whilst those of circulating immunoglobulin decreased. Conclusions: MSC may represent a promising tool to treat AE, but the lack of long-lasting benefit should be considered when planning this therapy. Our results also suggest that MSC transplantation has robust immunological effects in vivo.
P.18.5 DEVELOPMENT OF TREATMENT-SPECIFIC QUESTIONNAIRES FOR THE ASSESSMENT OF QUALITY OF LIFE OF PATIENTS ON HOME PARENTERAL NUTRITION (HPN) AND OF INTESTINAL TRANSPLANTATION (ITX) RECIPIENTS L. Pironi ∗ ,1 , J. Baxter 2 , A. Lauro 3 , M. Guidetti 1 , F. Agostini 1 , C. Zanfi 3 , A.D. Pinna 3 1 Center For Chronic Intestinal Failure, St. Orsola-Malpighi Hospital, Bologna, Italy; 2 Hospital and Medical School, Ninewells, United Kingdom; 3 Transplantation Unit, St. Orsola-Malpighi Hospital, Bologna, Italy
Background and aim: A treatment-specific quality of life questionnaire for adult patients on HPN (HPN-QOL©) has been recently validated (Baxter J, JPEN 2010;34:131). In order to investigate the quality of life on HPN and after ITx using comparable instruments, the HPN-QOL© was adapted to ITx recipients, by modifying the text of some items, without changing number of either the items or the scales. A cross-sectional study was performed to compare patients on HPN or who had undergone ITx. Material and methods: All the patients currently followed at the same Hospital were enrolled. Exclusion criteria were: age = 60 years and hospitalization at time of assessment. The questionnaire was administered at time of a scheduled visit at the outpatient clinic or was mailed at patient home. The HPN-QOL© is composed of both multi-item scales and single-item measures. These include 8 functional scales, 9 symptom scales, 3 global health status/quality of life scales and 2 single items. The Mann-Whitney U test was used for the statistical analysis. Results: Thirty-three HPN-patients and 18 ITx recipients received the questionnaires. All the HPN-patients (12 M, 21 F; median age: 46 yrs) and 16 ITx recipients (10 M, 6 F, p=0.08; median age 40.5 yrs, P=0.11) participated in the study. Two ITx recipients had a central venous catheter for hydration or HPN. ITx recipients showed a better score in the following scales: ability to holiday/travel (p=0.001, fatigue (p=0.026), gastrointestinal symptoms (p<0.001), stoma management/bowel movements (P=0.001). A trend toward an improvement was observed also in ability to eat/drink (p=0.063). No significant difference was observed in the other scales: general health, physical function, coping, employment, sexual function, emotional function, support by the nutritional team, body image, body weight, immobility, sleep pattern, non-gastrointestinal pain, financial issues. Conclusions: Specific and comparable questionnaires showed that those domains of the quality of life that are related to gastrointestinal function and symptoms and to general physical independency are improved after ITx in comparison with HPN.
Background and aim: Whipple’s disease (WD) is a very rare chronic multisystemic infection caused by Tropheryma whipplei (TW), a Gram-positive actinomycete, which in the majority of cases responds to a prolonged antibiotic treatment. In some patients the start of the treatment is, however, followed by the recurrence of a form of inflammation that does not respond any longer to antimicrobials but responds to steroids. Since polymerase chain reaction is negative for TW, this reinflammation cannot be a relapse of WD itself. Very recently, it has been recognised as a complication of WD and defined immune reconstitution inflammatory syndrome (IRIS). Aims: to study the prevalence and the clinical features of IRIS in WD patients attending our clinic. Material and methods: Between Jan 2000 and Sept 2011, 22 patients (4F, mean age 53.7±11.7 yrs) affected by WD attended our clinic. Evidence of IRIS, according to Feurle et al. [1], were retrospectively revaluated in the clinical notes. Patients with no evidence of IRIS served as controls for the clinical findings. Results: Recurrence of arthralgia (4 pts) and/or fever (2 pts) allowed a diagnosis of IRIS in 5/22 patients (22.7%). One patient died. Previous immunosuppressive therapy was found in 5/5 patients with IRIS but only in 7/17 controls (Fisher test, p=0.039). Both age at diagnosis (58.4±11.9 vs. 52.3±11.7 yrs) and diagnostic delay (6.6±3.5 vs. 4.7±3.5 yrs) were higher in patients with IRIS compared to controls. However, statistically significance was not reached. Probably because of the relatively small sample, clinical features and HLA did not differ between patients and controls. Conclusions: IRIS is a rather frequent complications of WD that must be promptly recognised because its course can be fatal. The risk of IRIS is greatly increased in patients previously treated with immunosuppressive therapy. Prospective studies are required to better define the clinical features of this complication of WD. Reference: [1] Feurle GE et al, Ann Intern Med 2010;153:710-7.
P.18.4 USE OF AUTOLOGOUS BONE MARROW-DERIVED MESENCHYMAL STROMAL CELL (MSC) TRANSPLANTATION AS RESCUE THERAPY FOR ADULT AUTOIMMUNE ENTEROPATHY R. Ciccocioppo ∗ ,1 , M.L. Russo 1 , F. Biagi 1 , M.E. Bernardo 2 , M.A. Avanzini 3 , A. Gallia 1 , V. Boccaccio 1 , V. Imbesi 1 , F. Racca 1 , A. Vanoli 4 , L. Catenacci 3 , F. Locatelli 5 , G.R. Corazza 1 1 Clinica Medica I, Fondazione Irccs Policlinico San Matteo, Università degli Studi di Pavia, Pavia, Italy; 2 Dipartimento di Oncoematologia Pediatrica e Medicina Trasfusionale, Ospedale Bambino Gesù, Roma, Italy; 3 Laboratorio di Immunologia e Trapianti, Oncoematologia Pediatrica, Fondazione Irccs Policlinico San Matteo, Pavia, Italy; 4 Servizio di Anatomia Patologica, Fondazione Irccs Policlinico S. Matteo, Università degli Studi di Pavia, Pavia, Italy; 5 Dipartimento di Oncoematologia Pediatrica e Medicina Trasfusionale, Ospedale Bambino Gesù, Università degli Studi di Pavia, Roma, Pavia, Italy
Background and aim: Adult autoimmune enteropathy (AE) is a rare condition characterized by the presence of anti-enterocyte antibodies (AEA) and small bowel villous atrophy causing severe malabsorption. Its treatment is based on immunosuppressive or biological therapy, with parenteral nutrition reserved to severe cases. MSC, thanks to their regenerative and immunomodulatory function, was successful to treat AE in a mice model of multiorgan autoimmunity due to mutation of Foxp3, a transcriptor factor expressed by regulatory T cells. We used autologous bone-marrow MSC transplantation as rescue therapy in a 61-year old woman with life-threatening malabsorption syndrome due to AE refractory to steroid therapy.
S205
Material and methods: MSC were isolated and expanded ex vivo following standardized protocol. AEA were tested by indirect immunofluorescence. Circulating and mucosal Foxp3+ T cells were detected by flow-cytometry and immunohistochemistry on duodenal biopsies, respectively. Secretory IgA (sIgA) were quantified in saliva samples by electroimmunodiffusion assay. Results: MSC expansion was successful thus allowing 2 systemic infusion of 1,8×106 MSC/pro kg two weeks a part without adverse effects. During the first month after transplantation, the patient experienced wellbeing and regularization of both stool frequency and body weight. At this time, the positivity of AEA was no longer detected and a patchy recovery of duodenal mucosa was evident. After a further month, she had relapse and an additional MSC infusion at the same dose was performed allowing a transient wellness. Total parenteral nutrition and steroid therapy were, therefore, re-established leading to satisfactory clinical conditions and negativity of both serological and histological findings. Remarkably, after each MSC transplantation, a transient mucosal enrichment and peripheral blood depletion of FoxP3+ T cells were observed. The levels of sIgA were found increased upon MSC infusions, whilst those of circulating immunoglobulin decreased. Conclusions: MSC may represent a promising tool to treat AE, but the lack of long-lasting benefit should be considered when planning this therapy. Our results also suggest that MSC transplantation has robust immunological effects in vivo.
P.18.5 DEVELOPMENT OF TREATMENT-SPECIFIC QUESTIONNAIRES FOR THE ASSESSMENT OF QUALITY OF LIFE OF PATIENTS ON HOME PARENTERAL NUTRITION (HPN) AND OF INTESTINAL TRANSPLANTATION (ITX) RECIPIENTS L. Pironi ∗ ,1 , J. Baxter 2 , A. Lauro 3 , M. Guidetti 1 , F. Agostini 1 , C. Zanfi 3 , A.D. Pinna 3 1 Center For Chronic Intestinal Failure, St. Orsola-Malpighi Hospital, Bologna, Italy; 2 Hospital and Medical School, Ninewells, United Kingdom; 3 Transplantation Unit, St. Orsola-Malpighi Hospital, Bologna, Italy
Background and aim: A treatment-specific quality of life questionnaire for adult patients on HPN (HPN-QOL©) has been recently validated (Baxter J, JPEN 2010;34:131). In order to investigate the quality of life on HPN and after ITx using comparable instruments, the HPN-QOL© was adapted to ITx recipients, by modifying the text of some items, without changing number of either the items or the scales. A cross-sectional study was performed to compare patients on HPN or who had undergone ITx. Material and methods: All the patients currently followed at the same Hospital were enrolled. Exclusion criteria were: age = 60 years and hospitalization at time of assessment. The questionnaire was administered at time of a scheduled visit at the outpatient clinic or was mailed at patient home. The HPN-QOL© is composed of both multi-item scales and single-item measures. These include 8 functional scales, 9 symptom scales, 3 global health status/quality of life scales and 2 single items. The Mann-Whitney U test was used for the statistical analysis. Results: Thirty-three HPN-patients and 18 ITx recipients received the questionnaires. All the HPN-patients (12 M, 21 F; median age: 46 yrs) and 16 ITx recipients (10 M, 6 F, p=0.08; median age 40.5 yrs, P=0.11) participated in the study. Two ITx recipients had a central venous catheter for hydration or HPN. ITx recipients showed a better score in the following scales: ability to holiday/travel (p=0.001, fatigue (p=0.026), gastrointestinal symptoms (p<0.001), stoma management/bowel movements (P=0.001). A trend toward an improvement was observed also in ability to eat/drink (p=0.063). No significant difference was observed in the other scales: general health, physical function, coping, employment, sexual function, emotional function, support by the nutritional team, body image, body weight, immobility, sleep pattern, non-gastrointestinal pain, financial issues. Conclusions: Specific and comparable questionnaires showed that those domains of the quality of life that are related to gastrointestinal function and symptoms and to general physical independency are improved after ITx in comparison with HPN.