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Monitoring of circulating autoantibodies in celiac patients on a strict gluten-free diet
April 2000
indirect immune fluorescence test with monkey esophagus as substrate. The antibody levels in different populations studied were expressed relative to the new reference serum as Dutch Units (DU). The use of a positive standard will simplify comparison of data reported in different studies and it can constitute a suitable way to solve practical problems of quality control for serologic assays. We prepared a large quantity of the positive reference serum which can be used by many laboratories for an unlimited time.
1971 CORRELATION OF BIOPSY FINDINGS AND ENDOMYSIAL ANTIBODY STATUS WITH DISEASE SEVERITY IN PATIENTS WITH CELIAC DISEASE. Vipul H. Shah, Winson Lo, Heidrun Rotterdam, Susie K. Lee, Neeraj Katriyar, Peter Hr Green, Columbia Univ Coli of Physicians and Surgeons, New York, NY; Columbia Univ, New York, NY. Aim: Our aim is to correlate 1.) the number of biopsy pieces with the diagnosis of villous atrophy, and 2.) the severity of disease with the endomysial antibody (EMA) status. Methods: We reviewed duodenal biopsies from 76 patients with celiac disease (CD) as defined by ESPGAN criteria. A single pathologist (UR) reviewed all biopsies. Biopsy pieces were classified as interpretable if at least 4 villi were properly oriented. Villous atrophy (VA) was defined as total (TVA) if the V:C ratio was <1:1 or zero and as partial (PVA) if the ratio was 1:1 to 3:1. We defined the disease as diffuse if all interpretable biopsy pieces showed VA and as patchy if at least 1 biopsy piece was normal. Results: 31 of the 76 patients with CD were biopsied prior to a gluten free diet (GFD) and 43 after a GFD. There was a total of 456 biopsies, yielding 223 (49%) interpretable pieces and 203 (44%) with VA On the average 6::':2.8 biopsies were taken per patient and yielded 2.9::':1.9 interpretable and 2.7::':1.6 with VA Among patients with TVA, 29/40 (73%) had diffuse disease and 1/40 (2%) had patchy disease. In 10/40 (25%) there was only 1 interpretable biopsy piece. Among patients with PVA, 17/33 (51%) had diffuse disease and 13/33 (39%) had patchy disease. In 3/33 (10%) patients there was only 1 interpretable piece. Patchy disease was more commonly found in patients with PVA compared to TVA (39% vs 2%, p<. 001). EMA was performed in 75 patients. Prior to GFD 58% were EMA (+) while on GFD only 9% were EMA (+) despite the presence of VA, p< .05. Among patients with TVA prior to GFD, 83% were EMA (+) vs. 23% that were EMA (-), p< .001. Conclusion: Less than half of duodenal biopsy pieces were oriented sufficiently to allow evaluation of VA. CD is a patchy disease especially in patients with a less severe form (PVA) and therefore requires a more intensive biopsy regimen. VA persists despite gluten withdrawal. EMA positivity is correlated with more severe histologic findings and with gluten ingestion.
1972 HEALTH RELATED QUALITY OF LIFE EVALUATION IN ADULT CELIAC DISEASE. Paolo Usai, Luigi Minerba, Roberto Ariu, Barbara Marini, Roberta Cossu, Simone Spada, Francesca M. Boi, Dept Science Medicine Internistiche, Cagliari, Italy; Dept di Igiene, Cagliari, Italy. Background: Interest in measuring Healt Related Quality Of Life (HRQOL) in chronic disease has increased in recent years in defining the natural history of disease and evaluating the outcomes of various treatment. Celiac (CD) is a chronic sensitive disease gluten enteropathy, characterized by small intestinal mucosal injury, by a varying clinical picture and often associated to other autoimmune disorders. Restoration of the villous following atrophy and clinical improvement is observed after gluten free diet (OFD) institution. Aim: The aim of our study was to detect in adult CD if HRQOL is related to: 1) adhesion to GFD; 2) number of symptoms at diagnosis; 3) associated diseases. Patients and methods: In sixty six patients with CD 53 female, 13 male aged between 18 years and 74 years on GFD from at least two years, were somministrated two questionnaires: a standard questionnaire to asses adhesion to GFD and symptoms at diag-
AGAA371
nosis and a standard questionnaire SF-36 for HRQOL, associated diseases were also recorded. For SF-36 scores were calculated from patients answers and transformed from 0 to 100 (0= complete dysfunction, 100 = no dysfunction), while GFD adhesion were graded in complete adhesion, partial adhesion, no adhesion, symptoms were graded in accordance with the number more than six. One hundred thirty six healthy subjects, were examined as the control group. Results: Patients were found to score generally worse than healthy controls in all domains (PsO.05), adhesion to GFD improves within the Role Emotional (RE), Bodily Pain (BP), Mental Health (MH) and Social Functioning (SF) domains, patients declaring less compliance to GFD scored lower than those keeping a strict diet in MH and SF (PSO.05), the lowest scores were obtained in patients with more than six symptoms at diagnosis, mostly in those with partial GFD in all domains (PSO.05) except in MH, scores of patients with associated diseases were similar to those without associated diseases. Conclusions: HRQOL scores of celiac patients were significantly lower than controls, GFD showed a pivotal role in improving HRQOL, in fact scores of patients on GFD were similar to those obtained in controls, moreover the number of symptoms at diagnosis was an important factor in worsening HRQOL also in patients on GFD.
1973 MONITORING OF CIRCULATING AUTOANTIBODIES IN CELIAC PATIENTS ON A STRICT GLUTEN-FREE DIET. Franca Viola, Maria Barbato, M. A. Arnendolea, Mario Curione, Lucia Franchin, Lucia Dito, L. D' Aviera, Lelia La Russo, Tullio Frediani, D. Lendvai, C. Masala, Ettore Cardi, Dept of Pediatric Gastroenterology, Rome, Italy; Service for Autoimmune Diseases, Rome, Italy; Dept of Clin Sci, Rome, Italy. F. Viola, M.Barbato, *M.A.Amendolea, **M.Curione, L.Franchin, L.Dito, *L.D' Aviera, L.Lo Russo, T'Frediani, S.Lucarelli, D.Lendvai, *C.Masala, E.Cardi. Department of Pediatric Gastroenterology * Service for Autoimmune Diseases ** Department of Clinical Sciences University of Rome "La Sapienza" As is known, celiac patients often develop other autoimmune disorders.(l) An our previous work noted that a high number of celiac patients present various organ-specific and non-organ-specific antibodies also in the absence of any overt illness.(2) It was decided to monitor the circulating autoantibodies in a small group of patients after a period of roughly two years in order to determine whether any variations had taken place. The following autoantibodies were monitored in 20 celiac patients (mean age, 13 years) on a strict gluten-free diet for at least two years: antinuclear antibodies (ANA), mitochondrial antibodies (AMA), smooth muscle antibodies (SMA), gastric parietal cells antibodies (PCA), thyroglobulin antibodies (TgA), thyroid peroxidase antibodies (TMAlTPO-A), antineutrophil cytoplasmic autoantibodies (ANCA). As the table shows, three patients had developed anti-thyroid antibodies, which were absent in the previous assay, while six had developed ANA, which were again previously absent. It thus emerges that organ-specific and non-organspecific antibodies can appear over time even in celiac patients following a strict diet. As pointed out in a previous work,(2) ANA appear to be the most frequent (12120). It is therefore useful that celiac patients be subjected to periodical monitoring of circulating antibodies. Further monitoring over time and a greater wealth of case histories will serve to reveal whether the presence of these autoantibodies in the absence of clinical signs of illness possesses any predictive value as regards the development of another autoimmune pathology. Bibliography 1) AVentura et al., Gastroenterology 1999; 117: 297-303 2) M.Barbato et aI., Digestion 1998; 54 (3s): 685
Circulating autoantibodies
ANA I assay II assay
6 12
TgA
TgA!TPO
PCA
SMA
AMA
ANCA
indirect immune fluorescence test with monkey esophagus as substrate. The antibody levels in different populations studied were expressed relative to the new reference serum as Dutch Units (DU). The use of a positive standard will simplify comparison of data reported in different studies and it can constitute a suitable way to solve practical problems of quality control for serologic assays. We prepared a large quantity of the positive reference serum which can be used by many laboratories for an unlimited time.
1971 CORRELATION OF BIOPSY FINDINGS AND ENDOMYSIAL ANTIBODY STATUS WITH DISEASE SEVERITY IN PATIENTS WITH CELIAC DISEASE. Vipul H. Shah, Winson Lo, Heidrun Rotterdam, Susie K. Lee, Neeraj Katriyar, Peter Hr Green, Columbia Univ Coli of Physicians and Surgeons, New York, NY; Columbia Univ, New York, NY. Aim: Our aim is to correlate 1.) the number of biopsy pieces with the diagnosis of villous atrophy, and 2.) the severity of disease with the endomysial antibody (EMA) status. Methods: We reviewed duodenal biopsies from 76 patients with celiac disease (CD) as defined by ESPGAN criteria. A single pathologist (UR) reviewed all biopsies. Biopsy pieces were classified as interpretable if at least 4 villi were properly oriented. Villous atrophy (VA) was defined as total (TVA) if the V:C ratio was <1:1 or zero and as partial (PVA) if the ratio was 1:1 to 3:1. We defined the disease as diffuse if all interpretable biopsy pieces showed VA and as patchy if at least 1 biopsy piece was normal. Results: 31 of the 76 patients with CD were biopsied prior to a gluten free diet (GFD) and 43 after a GFD. There was a total of 456 biopsies, yielding 223 (49%) interpretable pieces and 203 (44%) with VA On the average 6::':2.8 biopsies were taken per patient and yielded 2.9::':1.9 interpretable and 2.7::':1.6 with VA Among patients with TVA, 29/40 (73%) had diffuse disease and 1/40 (2%) had patchy disease. In 10/40 (25%) there was only 1 interpretable biopsy piece. Among patients with PVA, 17/33 (51%) had diffuse disease and 13/33 (39%) had patchy disease. In 3/33 (10%) patients there was only 1 interpretable piece. Patchy disease was more commonly found in patients with PVA compared to TVA (39% vs 2%, p<. 001). EMA was performed in 75 patients. Prior to GFD 58% were EMA (+) while on GFD only 9% were EMA (+) despite the presence of VA, p< .05. Among patients with TVA prior to GFD, 83% were EMA (+) vs. 23% that were EMA (-), p< .001. Conclusion: Less than half of duodenal biopsy pieces were oriented sufficiently to allow evaluation of VA. CD is a patchy disease especially in patients with a less severe form (PVA) and therefore requires a more intensive biopsy regimen. VA persists despite gluten withdrawal. EMA positivity is correlated with more severe histologic findings and with gluten ingestion.
1972 HEALTH RELATED QUALITY OF LIFE EVALUATION IN ADULT CELIAC DISEASE. Paolo Usai, Luigi Minerba, Roberto Ariu, Barbara Marini, Roberta Cossu, Simone Spada, Francesca M. Boi, Dept Science Medicine Internistiche, Cagliari, Italy; Dept di Igiene, Cagliari, Italy. Background: Interest in measuring Healt Related Quality Of Life (HRQOL) in chronic disease has increased in recent years in defining the natural history of disease and evaluating the outcomes of various treatment. Celiac (CD) is a chronic sensitive disease gluten enteropathy, characterized by small intestinal mucosal injury, by a varying clinical picture and often associated to other autoimmune disorders. Restoration of the villous following atrophy and clinical improvement is observed after gluten free diet (OFD) institution. Aim: The aim of our study was to detect in adult CD if HRQOL is related to: 1) adhesion to GFD; 2) number of symptoms at diagnosis; 3) associated diseases. Patients and methods: In sixty six patients with CD 53 female, 13 male aged between 18 years and 74 years on GFD from at least two years, were somministrated two questionnaires: a standard questionnaire to asses adhesion to GFD and symptoms at diag-
AGAA371
nosis and a standard questionnaire SF-36 for HRQOL, associated diseases were also recorded. For SF-36 scores were calculated from patients answers and transformed from 0 to 100 (0= complete dysfunction, 100 = no dysfunction), while GFD adhesion were graded in complete adhesion, partial adhesion, no adhesion, symptoms were graded in accordance with the number more than six. One hundred thirty six healthy subjects, were examined as the control group. Results: Patients were found to score generally worse than healthy controls in all domains (PsO.05), adhesion to GFD improves within the Role Emotional (RE), Bodily Pain (BP), Mental Health (MH) and Social Functioning (SF) domains, patients declaring less compliance to GFD scored lower than those keeping a strict diet in MH and SF (PSO.05), the lowest scores were obtained in patients with more than six symptoms at diagnosis, mostly in those with partial GFD in all domains (PSO.05) except in MH, scores of patients with associated diseases were similar to those without associated diseases. Conclusions: HRQOL scores of celiac patients were significantly lower than controls, GFD showed a pivotal role in improving HRQOL, in fact scores of patients on GFD were similar to those obtained in controls, moreover the number of symptoms at diagnosis was an important factor in worsening HRQOL also in patients on GFD.
1973 MONITORING OF CIRCULATING AUTOANTIBODIES IN CELIAC PATIENTS ON A STRICT GLUTEN-FREE DIET. Franca Viola, Maria Barbato, M. A. Arnendolea, Mario Curione, Lucia Franchin, Lucia Dito, L. D' Aviera, Lelia La Russo, Tullio Frediani, D. Lendvai, C. Masala, Ettore Cardi, Dept of Pediatric Gastroenterology, Rome, Italy; Service for Autoimmune Diseases, Rome, Italy; Dept of Clin Sci, Rome, Italy. F. Viola, M.Barbato, *M.A.Amendolea, **M.Curione, L.Franchin, L.Dito, *L.D' Aviera, L.Lo Russo, T'Frediani, S.Lucarelli, D.Lendvai, *C.Masala, E.Cardi. Department of Pediatric Gastroenterology * Service for Autoimmune Diseases ** Department of Clinical Sciences University of Rome "La Sapienza" As is known, celiac patients often develop other autoimmune disorders.(l) An our previous work noted that a high number of celiac patients present various organ-specific and non-organ-specific antibodies also in the absence of any overt illness.(2) It was decided to monitor the circulating autoantibodies in a small group of patients after a period of roughly two years in order to determine whether any variations had taken place. The following autoantibodies were monitored in 20 celiac patients (mean age, 13 years) on a strict gluten-free diet for at least two years: antinuclear antibodies (ANA), mitochondrial antibodies (AMA), smooth muscle antibodies (SMA), gastric parietal cells antibodies (PCA), thyroglobulin antibodies (TgA), thyroid peroxidase antibodies (TMAlTPO-A), antineutrophil cytoplasmic autoantibodies (ANCA). As the table shows, three patients had developed anti-thyroid antibodies, which were absent in the previous assay, while six had developed ANA, which were again previously absent. It thus emerges that organ-specific and non-organspecific antibodies can appear over time even in celiac patients following a strict diet. As pointed out in a previous work,(2) ANA appear to be the most frequent (12120). It is therefore useful that celiac patients be subjected to periodical monitoring of circulating antibodies. Further monitoring over time and a greater wealth of case histories will serve to reveal whether the presence of these autoantibodies in the absence of clinical signs of illness possesses any predictive value as regards the development of another autoimmune pathology. Bibliography 1) AVentura et al., Gastroenterology 1999; 117: 297-303 2) M.Barbato et aI., Digestion 1998; 54 (3s): 685
Circulating autoantibodies
ANA I assay II assay
6 12
TgA
TgA!TPO
PCA
SMA
AMA
ANCA