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1
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34247633114
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Clinical presentation and incidence of complications in patients with coeliac disease diagnosed by relative screening
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This study compared clinical features in coeliac disease patients detected via routine testing with those diagnosed through family screening. It highlights the potential advantage of utilizing relative screening
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Sundar N, Crimmins R, Swift G. Clinical presentation and incidence of complications in patients with coeliac disease diagnosed by relative screening. Postgrad Med J 2007; 83:273-276. This study compared clinical features in coeliac disease patients detected via routine testing with those diagnosed through family screening. It highlights the potential advantage of utilizing relative screening.
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(2007)
Postgrad Med J
, vol.83
, pp. 273-276
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Sundar, N.1
Crimmins, R.2
Swift, G.3
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2
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0037429081
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Prevalence of celiac disease in at-risk and not-at-risk groups in the United States: A large multicenter study
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Fasano A, Berti I, Gerarduzzi T, et al. Prevalence of celiac disease in at-risk and not-at-risk groups in the United States: a large multicenter study. Arch Intern Med 2003; 163:286-292.
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(2003)
Arch Intern Med
, vol.163
, pp. 286-292
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Fasano, A.1
Berti, I.2
Gerarduzzi, T.3
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3
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33947598400
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Goldberg D, Kryszak D, Fasano A, Green PH. Screening for celiac disease in family members: is follow-up testing necessary? Dig Dis Sci 2007; 52:1082-1086. Using a database maintained at the University of Maryland Center for Celiac Research, USA, the authors aimed to assess whether one-time screening of family members is sufficient and to establish the time interval for repeat testing in those family members who initially tested negative. The conclusion was that one-time testing in individuals is insufficient.
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Goldberg D, Kryszak D, Fasano A, Green PH. Screening for celiac disease in family members: is follow-up testing necessary? Dig Dis Sci 2007; 52:1082-1086. Using a database maintained at the University of Maryland Center for Celiac Research, USA, the authors aimed to assess whether one-time screening of family members is sufficient and to establish the time interval for repeat testing in those family members who initially tested negative. The conclusion was that one-time testing in individuals is insufficient.
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4
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33845416143
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Esteve M, Rosinach M, Fernandez-Banares F, et al. Spectrum of glutensensitive enteropathy in first-degree relatives of patients with coeliac disease: clinical relevance of lymphocytic enteritis. Gut 2006; 55:1739-1745. This study included 221 first-degree relatives of 82 DQ2-positive patients with coeliac disease. The authors showed that a high number of patients with Marsh 1 lesions were symptomatic for abdominal distension and pain. In summary, the study shows the potential benefit a GFD would have for such patients, and it substantiates the need for other diagnostic strategies to improve coeliac disease detection rates and the potential role that HLA-DQ2 genotyping may play in this matter.
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Esteve M, Rosinach M, Fernandez-Banares F, et al. Spectrum of glutensensitive enteropathy in first-degree relatives of patients with coeliac disease: clinical relevance of lymphocytic enteritis. Gut 2006; 55:1739-1745. This study included 221 first-degree relatives of 82 DQ2-positive patients with coeliac disease. The authors showed that a high number of patients with Marsh 1 lesions were symptomatic for abdominal distension and pain. In summary, the study shows the potential benefit a GFD would have for such patients, and it substantiates the need for other diagnostic strategies to improve coeliac disease detection rates and the potential role that HLA-DQ2 genotyping may play in this matter.
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5
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34547164912
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Bourgey M, Calcagno G, Tinto N, et al. HLA related genetic risk for coeliac disease. Gut 2007; 56:1054-1059. This study of a cohort of 188 Italian families was conducted to evaluate the risk that siblings of children with coeliac disease will also develop coeliac disease and to genotype all family members. Such studies provide direction for calculating coeliac disease risk, thus potentially tailoring screening to an individual's risk in the antenatal setting.
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Bourgey M, Calcagno G, Tinto N, et al. HLA related genetic risk for coeliac disease. Gut 2007; 56:1054-1059. This study of a cohort of 188 Italian families was conducted to evaluate the risk that siblings of children with coeliac disease will also develop coeliac disease and to genotype all family members. Such studies provide direction for calculating coeliac disease risk, thus potentially tailoring screening to an individual's risk in the antenatal setting.
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6
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Hopper AD, Cross SS, Hurlstone DP, et al. Preendoscopy serological testing for coeliac disease: evaluation of a clinical decision tool. BMJ 2007; 334:729-733. Using a retrospective analysis the authors analysed data from 1464 unselected patients who had undergone duodenal biopsy. Their aim was to develop an effective diagnosis tool for detecting all cases of coeliac disease in patients referred for gastroscopy without performing duodenal biopsy. Alongside cost-effectiveness, the study has implications for avoiding the need to do duodenal biopsies in low-risk patients.
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Hopper AD, Cross SS, Hurlstone DP, et al. Preendoscopy serological testing for coeliac disease: evaluation of a clinical decision tool. BMJ 2007; 334:729-733. Using a retrospective analysis the authors analysed data from 1464 unselected patients who had undergone duodenal biopsy. Their aim was to develop an effective diagnosis tool for detecting all cases of coeliac disease in patients referred for gastroscopy without performing duodenal biopsy. Alongside cost-effectiveness, the study has implications for avoiding the need to do duodenal biopsies in low-risk patients.
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7
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33947281785
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Shamir R, Yehezkely-Schildkraut V, Hartman C, Eliakim R. Population screening for celiac disease: follow up of patients identified by positive serology. J Gastroenterol Hepatol 2007; 22:532-535. The authors offered endoscopy with intestinal biopsy to the 59 patients with positive serology from their original study on the prevalence of coeliac disease in healthy blood donors in Israel. They found that investigation and management of coeliac disease still has obstacles to overcome if coeliac disease screening is to provide enhanced health benefits.
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Shamir R, Yehezkely-Schildkraut V, Hartman C, Eliakim R. Population screening for celiac disease: follow up of patients identified by positive serology. J Gastroenterol Hepatol 2007; 22:532-535. The authors offered endoscopy with intestinal biopsy to the 59 patients with positive serology from their original study on the prevalence of coeliac disease in healthy blood donors in Israel. They found that investigation and management of coeliac disease still has obstacles to overcome if coeliac disease screening is to provide enhanced health benefits.
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8
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33744832433
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Diagnostic accuracy of coeliac serological tests: A prospective study
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A prospective multicentre serology study was performed throughout Australia. It was found that dual-isotype tTG is a sensitive and specific alternative to EMA testing in the serological assessment of coeliac disease
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Reeves GE, Squance ML, Duggan AE, et al. Diagnostic accuracy of coeliac serological tests: a prospective study. Eur J Gastroenterol Hepatol 2006; 18:493-501. A prospective multicentre serology study was performed throughout Australia. It was found that dual-isotype tTG is a sensitive and specific alternative to EMA testing in the serological assessment of coeliac disease.
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(2006)
Eur J Gastroenterol Hepatol
, vol.18
, pp. 493-501
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Reeves, G.E.1
Squance, M.L.2
Duggan, A.E.3
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9
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Sinclair D, Saas M, Turk A, et al. Do we need to measure total serum IgA to exclude IgA deficiency in coeliac disease? J Clin Pathol 2006; 59:736-739. The authors at the Department of Clinical Biochemistry at the Queen Alexandra Hospital, Portsmouth, UK utilized optical density readings on enzyme-linked immunosorbent assay of 608 routine samples received for tTG testing for coeliac disease and compared them with total IgA concentrations. In brief, they identified an easier and more cost-effective and practical way to exclude IgA deficiency in coeliac disease.
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Sinclair D, Saas M, Turk A, et al. Do we need to measure total serum IgA to exclude IgA deficiency in coeliac disease? J Clin Pathol 2006; 59:736-739. The authors at the Department of Clinical Biochemistry at the Queen Alexandra Hospital, Portsmouth, UK utilized optical density readings on enzyme-linked immunosorbent assay of 608 routine samples received for tTG testing for coeliac disease and compared them with total IgA concentrations. In brief, they identified an easier and more cost-effective and practical way to exclude IgA deficiency in coeliac disease.
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10
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0033800238
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Immune reaction against the cytoskeleton in coeliac disease
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Clemente MG, Musu MP, Frau F, et al. Immune reaction against the cytoskeleton in coeliac disease. Gut 2000; 47:520-526.
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(2000)
Gut
, vol.47
, pp. 520-526
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Clemente, M.G.1
Musu, M.P.2
Frau, F.3
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11
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Enterocyte actin autoantibody detection: A new diagnostic tool in celiac disease diagnosis: results of a multicenter study
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Clemente MG, Musu MP, Troncone R, et al. Enterocyte actin autoantibody detection: a new diagnostic tool in celiac disease diagnosis: results of a multicenter study. Am J Gastroenterol 2004; 99:1551-1556.
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(2004)
Am J Gastroenterol
, vol.99
, pp. 1551-1556
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Clemente, M.G.1
Musu, M.P.2
Troncone, R.3
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Carroccio A, Brusca I, Iacono G, et al. IgA antiactin antibodies ELISA in coeliac disease: a multicentre study. Dig Liver Dis 2007; 39:818-823. In this study four centres in Italy recruited 205 newly diagnosed coeliac disease patients with villous atrophy between January and December 2004. The authors aimed to evaluate the clinical usefulness of serum IgA-AAA in monitoring intestinal mucosal lesions while taking a GFD. They concluded that using simple ELISA IgA-AAA is a reliable marker of severe intestinal damage.
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Carroccio A, Brusca I, Iacono G, et al. IgA antiactin antibodies ELISA in coeliac disease: a multicentre study. Dig Liver Dis 2007; 39:818-823. In this study four centres in Italy recruited 205 newly diagnosed coeliac disease patients with villous atrophy between January and December 2004. The authors aimed to evaluate the clinical usefulness of serum IgA-AAA in monitoring intestinal mucosal lesions while taking a GFD. They concluded that using simple ELISA IgA-AAA is a reliable marker of severe intestinal damage.
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Identification of the haemoglobin scavenger receptor
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Kristiansen M, Graversen JH, Jacobsen C, et al. Identification of the haemoglobin scavenger receptor. Nature 2001; 409:198-201.
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(2001)
Nature
, vol.409
, pp. 198-201
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Kristiansen, M.1
Graversen, J.H.2
Jacobsen, C.3
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14
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33745910232
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Daly A, Walsh C, Feighery C, et al. Serum levels of soluble CD163 correlate with the inflammatory process in coeliac disease. Aliment Pharmacol Ther 2006; 24:553-559. The authors from St James's Hospital Dublin, Ireland aimed to determine whether levels of soluble CD163 correlated with the inflammatory lesion in coeliac disease. Its use in evaluating the effectiveness of the diet in reducing the inflammatory lesion may have a prominent role in the future.
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Daly A, Walsh C, Feighery C, et al. Serum levels of soluble CD163 correlate with the inflammatory process in coeliac disease. Aliment Pharmacol Ther 2006; 24:553-559. The authors from St James's Hospital Dublin, Ireland aimed to determine whether levels of soluble CD163 correlated with the inflammatory lesion in coeliac disease. Its use in evaluating the effectiveness of the diet in reducing the inflammatory lesion may have a prominent role in the future.
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Increased protein expression of matrix metalloproteinases -1, -3, and -9 and TIMP-1 in patients with gluten-sensitive enteropathy
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Mohamed BM, Feighery C, Kelly J, et al. Increased protein expression of matrix metalloproteinases -1, -3, and -9 and TIMP-1 in patients with gluten-sensitive enteropathy. Dig Dis Sci 2006; 51:1862-1868.
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(2006)
Dig Dis Sci
, vol.51
, pp. 1862-1868
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Mohamed, B.M.1
Feighery, C.2
Kelly, J.3
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0033034038
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Increased expression of mRNA for matrix metalloproteinases-1 and -3 and tissue inhibitor of metalloproteinases-1 in intestinal biopsy specimens from patients with coeliac disease
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Daum S, Bauer U, Foss HD, et al. Increased expression of mRNA for matrix metalloproteinases-1 and -3 and tissue inhibitor of metalloproteinases-1 in intestinal biopsy specimens from patients with coeliac disease. Gut 1999; 44:17-25.
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(1999)
Gut
, vol.44
, pp. 17-25
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Daum, S.1
Bauer, U.2
Foss, H.D.3
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17
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Matrix metalloproteinase pattern in celiac duodenal mucosa
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Ciccocioppo R, Di SA, Bauer M, et al. Matrix metalloproteinase pattern in celiac duodenal mucosa. Lab Invest 2005; 85:397-407.
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(2005)
Lab Invest
, vol.85
, pp. 397-407
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Ciccocioppo, R.1
Di, S.A.2
Bauer, M.3
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Salmi TT, Collin P, Korponay-Szabo IR, et al. Endomysial antibody-negative coeliac disease: clinical characteristics and intestinal autoantibody deposits. Gut 2006; 55:1746-1753. These Finnish authors set out to evaluate the clinical and histological features of EMA-negative coeliac disease, and to examine whether EMA equivalent autoantibodies against tTG can be seen in the small bowel mucosa when absent in the serum. They concluded that the detection of tTG in small bowel mucosa may be of future use, particularly in those patients who are seronegative for coeliac disease.
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Salmi TT, Collin P, Korponay-Szabo IR, et al. Endomysial antibody-negative coeliac disease: clinical characteristics and intestinal autoantibody deposits. Gut 2006; 55:1746-1753. These Finnish authors set out to evaluate the clinical and histological features of EMA-negative coeliac disease, and to examine whether EMA equivalent autoantibodies against tTG can be seen in the small bowel mucosa when absent in the serum. They concluded that the detection of tTG in small bowel mucosa may be of future use, particularly in those patients who are seronegative for coeliac disease.
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HLA-DQB1*0201 homozygosis predisposes to severe intestinal damage in celiac disease
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Jores RD, Frau F, Cucca F, et al. HLA-DQB1*0201 homozygosis predisposes to severe intestinal damage in celiac disease. Scand J Gastroenterol 2007; 42:48-53.
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(2007)
Scand J Gastroenterol
, vol.42
, pp. 48-53
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Jores, R.D.1
Frau, F.2
Cucca, F.3
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A major non-HLA locus in celiac disease maps to chromosome 19
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van Belzen MJ, Meijer JW, Sandkuijl LA, et al. A major non-HLA locus in celiac disease maps to chromosome 19. Gastroenterology 2003; 125:1032-1041.
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(2003)
Gastroenterology
, vol.125
, pp. 1032-1041
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van Belzen, M.J.1
Meijer, J.W.2
Sandkuijl, L.A.3
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21
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Meta and pooled analysis of European coeliac disease data
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Babron MC, Nilsson S, Adamovic S, et al. Meta and pooled analysis of European coeliac disease data. Eur J Hum Genet 2003; 11:828-834.
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(2003)
Eur J Hum Genet
, vol.11
, pp. 828-834
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Babron, M.C.1
Nilsson, S.2
Adamovic, S.3
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Myosin IXB variant increases the risk of celiac disease and points toward a primary intestinal barrier defect
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Monsuur AJ, de Bakker PI, Alizadeh BZ, et al. Myosin IXB variant increases the risk of celiac disease and points toward a primary intestinal barrier defect. Nat Genet 2005; 37:1341-1344.
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(2005)
Nat Genet
, vol.37
, pp. 1341-1344
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Monsuur, A.J.1
de Bakker, P.I.2
Alizadeh, B.Z.3
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Hunt KA, Monsuur AJ, McArdle WL, et al. Lack of association of MYO9B genetic variants with coeliac disease in a British cohort. Gut 2006; 55:969-972. The authors aimed to assess the role in coeliac disease susceptibility of genetic variation in MYO9B, which previous studies have suggested may be a predisposing factor. They concluded that in their UK population genetic variation in MYO9B does not have a major influence on coeliac disease predisposition.
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Hunt KA, Monsuur AJ, McArdle WL, et al. Lack of association of MYO9B genetic variants with coeliac disease in a British cohort. Gut 2006; 55:969-972. The authors aimed to assess the role in coeliac disease susceptibility of genetic variation in MYO9B, which previous studies have suggested may be a predisposing factor. They concluded that in their UK population genetic variation in MYO9B does not have a major influence on coeliac disease predisposition.
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•], showing no association.
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•], showing no association.
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Wapenaar MC, Monsuur AJ, Poell J, et al. The SPINK gene family and celiac disease susceptibility. Immunogenetics 2007; 59:349-357. The Dutch authors aimed to assess the gut mucosal gene expression and genetic association of SPINK 1, 2, 4 and 5 in the Dutch coeliac disease population. The authors of this initial work were unable to find an association with coeliac disease.
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Wapenaar MC, Monsuur AJ, Poell J, et al. The SPINK gene family and celiac disease susceptibility. Immunogenetics 2007; 59:349-357. The Dutch authors aimed to assess the gut mucosal gene expression and genetic association of SPINK 1, 2, 4 and 5 in the Dutch coeliac disease population. The authors of this initial work were unable to find an association with coeliac disease.
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A genome-wide association study for celiac disease identifies risk variants in the region harboring IL2 and IL21
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van Heel DA, Franke L, Hunt KA, et al. A genome-wide association study for celiac disease identifies risk variants in the region harboring IL2 and IL21. Nat Genet 2007; 39:827-829.
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(2007)
Nat Genet
, vol.39
, pp. 827-829
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van Heel, D.A.1
Franke, L.2
Hunt, K.A.3
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+ IEL clones isolated from coeliac disease and noncoeliac disease biopsies. In summary, they found that the imbalance between functionally distinct IEL populations that reside in the small intestinal mucosa may play a role in the pathogenesis of coeliac disease.
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+ IEL clones isolated from coeliac disease and noncoeliac disease biopsies. In summary, they found that the imbalance between functionally distinct IEL populations that reside in the small intestinal mucosa may play a role in the pathogenesis of coeliac disease.
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Human intestinal alphabeta IEL clones in celiac disease show reduced IL-10 synthesis and enhanced IL-2 production
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Kolkowski EC, Fernandez MA, Pujol-Borrell R, Jaraquemada D. Human intestinal alphabeta IEL clones in celiac disease show reduced IL-10 synthesis and enhanced IL-2 production. Cell Immunol 2006; 244:1-9.
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(2006)
Cell Immunol
, vol.244
, pp. 1-9
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Kolkowski, E.C.1
Fernandez, M.A.2
Pujol-Borrell, R.3
Jaraquemada, D.4
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0030615214
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Association between alpha-betaTCR+CD4-CD8- T-cell deficiency and IDDM in NOD/Lt mice
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Baxter AG, Kinder SJ, Hammond KJ, et al. Association between alpha-betaTCR+CD4-CD8- T-cell deficiency and IDDM in NOD/Lt mice. Diabetes 1997; 46:572-582.
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(1997)
Diabetes
, vol.46
, pp. 572-582
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Baxter, A.G.1
Kinder, S.J.2
Hammond, K.J.3
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Selective reduction of T cells bearing invariant V alpha 24J alpha Q antigen receptor in patients with systemic sclerosis
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Sumida T, Sakamoto A, Murata H, et al. Selective reduction of T cells bearing invariant V alpha 24J alpha Q antigen receptor in patients with systemic sclerosis. J Exp Med 1995; 182:1163-1168.
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(1995)
J Exp Med
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, pp. 1163-1168
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Sumida, T.1
Sakamoto, A.2
Murata, H.3
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31
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Deficiency of invariant natural killer T cells in coeliac disease
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Grose RH, Cummins AG, Thompson FM. Deficiency of invariant natural killer T cells in coeliac disease. Gut 2007; 56:790-795.
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(2007)
Gut
, vol.56
, pp. 790-795
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Grose, R.H.1
Cummins, A.G.2
Thompson, F.M.3
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Polymorphisms of the TNF-alpha gene and risk of celiac disease in T1DM children
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Hermann C, Krikovszky D, Vasarhelyi B, et al. Polymorphisms of the TNF-alpha gene and risk of celiac disease in T1DM children. Pediatr Diabetes 2007; 8:138-141.
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(2007)
Pediatr Diabetes
, vol.8
, pp. 138-141
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Hermann, C.1
Krikovszky, D.2
Vasarhelyi, B.3
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Interleukin 15: A key to disrupted intraepithelial lymphocyte homeostasis and lymphomagenesis in celiac disease
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Mention JJ, Ben AM, Begue B, et al. Interleukin 15: a key to disrupted intraepithelial lymphocyte homeostasis and lymphomagenesis in celiac disease. Gastroenterology 2003; 125:730-745.
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(2003)
Gastroenterology
, vol.125
, pp. 730-745
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Mention, J.J.1
Ben, A.M.2
Begue, B.3
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Association between innate response to gliadin and activation of pathogenic T cells in coeliac disease
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Maiuri L, Ciacci C, Ricciardelli I, et al. Association between innate response to gliadin and activation of pathogenic T cells in coeliac disease. Lancet 2003; 362:30-37.
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(2003)
Lancet
, vol.362
, pp. 30-37
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Maiuri, L.1
Ciacci, C.2
Ricciardelli, I.3
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Benahmed M, Meresse B, Arnulf B, et al. Inhibition of TGF-beta signaling by IL-15: a new role for IL-15 in the loss of immune homeostasis in celiac disease. Gastroenterology 2007; 132:994-1008. This French study was conducted to investigate why the proinflammatory effects of IL-15 cannot efficiently be controlled by transforming growth factor-β in coeliac disease. Their study supplies evidence of the potential role of IL-15 in promoting and sustaining intestinal inflammation in coeliac disease through impairment of transforming growth factor-β signalling.
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Benahmed M, Meresse B, Arnulf B, et al. Inhibition of TGF-beta signaling by IL-15: a new role for IL-15 in the loss of immune homeostasis in celiac disease. Gastroenterology 2007; 132:994-1008. This French study was conducted to investigate why the proinflammatory effects of IL-15 cannot efficiently be controlled by transforming growth factor-β in coeliac disease. Their study supplies evidence of the potential role of IL-15 in promoting and sustaining intestinal inflammation in coeliac disease through impairment of transforming growth factor-β signalling.
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Kagnoff MF. Mucosal inflammation in celiac disease: interleukin-15 meets transforming growth factor beta-1. Gastroenterology 2007; 132:1174-1176. This compact report collates and summarizes the collecting body of research showing the pivotal role IL-15 plays in impeding transforming growth factor-β signalling in mucosal T-cells and hence its functional relevance in coeliac disease pathogenesis.
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Kagnoff MF. Mucosal inflammation in celiac disease: interleukin-15 meets transforming growth factor beta-1. Gastroenterology 2007; 132:1174-1176. This compact report collates and summarizes the collecting body of research showing the pivotal role IL-15 plays in impeding transforming growth factor-β signalling in mucosal T-cells and hence its functional relevance in coeliac disease pathogenesis.
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Involvement of macrophage migration inhibitory factor gene in celiac disease susceptibility
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This short communication from these Spanish authors describes their testing of the influence of two functional MIF promotor variants in coeliac disease susceptibility. Their work produces early evidence for the role of the MIF gene in coeliac disease development
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Nunez C, Rueda B, Martinez A, et al. Involvement of macrophage migration inhibitory factor gene in celiac disease susceptibility. Genes Immun 2007; 8:168-170. This short communication from these Spanish authors describes their testing of the influence of two functional MIF promotor variants in coeliac disease susceptibility. Their work produces early evidence for the role of the MIF gene in coeliac disease development.
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(2007)
Genes Immun
, vol.8
, pp. 168-170
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Nunez, C.1
Rueda, B.2
Martinez, A.3
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Abel M, Cellier C, Kumar N, et al. Adulthood-onset celiac disease is associated with intercellular adhesion molecule-1 (ICAM-1) gene polymorphism. Hum Immunol 2006; 67:612-617. The authors studied 180 unrelated French Caucasian patients. Their results indicate that intercellular adhesion molecule genetic variants may play a role in coeliac disease pathogenesis, but it is a small study.
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Abel M, Cellier C, Kumar N, et al. Adulthood-onset celiac disease is associated with intercellular adhesion molecule-1 (ICAM-1) gene polymorphism. Hum Immunol 2006; 67:612-617. The authors studied 180 unrelated French Caucasian patients. Their results indicate that intercellular adhesion molecule genetic variants may play a role in coeliac disease pathogenesis, but it is a small study.
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Gibert A, Espadaler M, Angel Canela M, et al. Consumption of glutenfree products: should the threshold value for trace amounts of gluten be at 20, 100 or 200 p. p. m.? Eur J Gastroenterol Hepatol 2006; 18:1187-1195.
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Gibert A, Espadaler M, Angel Canela M, et al. Consumption of glutenfree products: should the threshold value for trace amounts of gluten be at 20, 100 or 200 p. p. m.? Eur J Gastroenterol Hepatol 2006; 18:1187-1195.
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Catassi C, Fabiani E, Iacono G, et al. A prospective, double-blind, placebocontrolled trial to establish a safe gluten threshold for patients with celiac disease. Am J Clin Nutr 2007; 85:160-166. The objective in this study was to establish the safe threshold of prolonged exposure to trace amounts of gluten (i.e. contaminating gluten) using a multicenter, double-blind, placebo-controlled randomized trial in 49 adults with biopsy-proven coeliac disease who were being treated with a GFD for over 2 years. The investigators found that abnormal bowel morphology persisted in a significant portion of patients on a GFD.
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