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Clustering of Crohn's disease within affected sibships
Jean-Pierre Hugot, Jean-Pierre Cézard, Jean-Frédéric Colombel, Sven Almer, Curt Tysk, Sean Montague, Miquel Gassull, Steen Christensen, Yigael Finkel, Corinne Gower-Rousseau, R Modigliani, Habib Zouali, Suzanne Lesage, Mathias Chamaillard, Jeanne Macry, Gilles Thomas, Jean-Marc Victor & J Belaiche on behalf of and the GETAID
Crohn's disease (CD) is a complex genetic disorder for which aetiology is unknown. Recently, genetic factors for susceptibility have been described. Several genetic loci have been mapped and partially explain the familial aggregations of the disease. However, environmental factors may also contribute to these aggregations. We considered that if the role of non-genetic factors was negligible, CD patients would be randomly distributed in sibships with multiple affected siblings. On the other hand if there was a significant environmental contribution, the siblings would be affected non-randomly over exposure status. In order to test this hypothesis, we studied 102 sibships with two or more affected siblings. A statistical test, named Cluster of Affected Sibling Test or CAST, was developed, based on the exact calculation of the probability of observing a given number of clusters of affected siblings in multiplex families. The null hypothesis of a random distribution of affected siblings was rejected (P=0.005). The observed excess of affected sibling clusters indicates that birth order influences the disease status. Considering that an adjacent order of birth is a global estimate of environmental sharing, this observation strongly suggests that environmental factors contribute to the observed familial aggregations of the disease. This observation provides evidence that familial CD is a relevant tool for further studies of environmental factors and gene-environment interaction. More generally, the CAST statistics may be widely applicable to estimate the involvement of environmental factors in the aetiology of other binary traits which may be observed in multiple members of the same sibship.
A clustering of Crohn's disease in Mankato, Minnesota
H J Van Kruiningen, B J Freda
Infrequently, clusterings of Crohn's disease (CD) occur that suggest it is transmissible. We studied such a clustering. Graduates of the Mankato West High School Class of 1980 were contacted by mail and asked to respond, by self-addressed postcard, to a six-item questionnaire about inflammatory bowel disease and CD. Responses were followed-up by telephone contact and additional mailings. Two visits were made to Mankato, Minnesota, to interview individuals with CD, to obtain medical records, radiographs, and sera, and to study environmental risk factors. Of the 320 graduates of the class of 1980, 285 were contacted. Seven cases of CD were identified, the equivalent of a prevalence of 2,400/100,000. Concerns were discovered that CD may have emanated from recreational swimming. Fecal coliform counts in excess of 200/dL, the standard above which water is regarded as unsafe for recreational use, had been recorded year after year for the Blue Earth River at Mankato and for the Minnesota River. Recent fecal coliform counts (1993-1995) of Lake Washington, Lake German/Jefferson, and Lake Shetek were greater than 200/dL in 57%, 65%, and 62% of water samples. This clustering, in unrelated individuals, argues against a genetic cause for CD and suggests that environmental transmission occurred.
An in-depth study of Crohn's disease in two French families
H J Van Kruiningen 1 , J F Colombel, R W Cartun, R H Whitlock, M Koopmans, H O Kangro, J A Hoogkamp-Korstanje, M Lecomte-Houcke, M Devred, J C Paris, et al.
Abstract
Background: Two French families were investigated. In the first a husband, wife, and 4 children had Crohn's disease; in the second 7 of 11 children had the disease. There was no history of Crohn's disease in antecedent generations and no linkage to HLA haplotypes.
Methods: Methods included family interviews; review of medical records, radiographs, and pathology slides; serology; selective stool culture; enzyme-linked immunosorbent assay for fecal viral detection; and immunocytochemistry.
Results: In both families multiple cases occurred among siblings in 7-13-month periods. There appeared to be a 4-8-year recurrence of new disease in both families. Radiographs showed a remarkable similarity in the pattern of disease, confined to distal ileum and cecum, in the members of family 1. Examination for pathology showed granulomas in all 8 patients for whom tissues were available. Acid-fast organisms or Campylobacter-like organisms were not found in tissue sections, and immunocytochemistry was negative for mycobacteria and Yersinia. Stool cultures were negative for mycobacteria, Yersinia, and Mycoplasma. Torovirus and coronavirus antigens were not found in stool. Serology was negative for antibodies to Brucella, Yersinia, influenza, and three enteropathogenic viruses of animals.
Conclusions: The circumstances and data suggest that an infectious microorganism is responsible for these clusterings of Crohn's disease.
Clustering of Crohn's disease in a Cotswold village
R. N. ALLAN, P. PEASE, J. P. IBBOTSON
The first large cluster of patients with Crohn's disease, identified in the parish of Blockley, Gloucestershire is reported. Twelve patients with Crohn's disease have been identified of whom only two (a father and daughter) are known to be related. The age and sex distribution and macroscopic site of disease at diagnosis is similar to that expected in an unselected series. The identification of such a cluster suggests that environmental factors may be important in pathogenesis.
Jean-Pierre Hugot, Jean-Pierre Cézard, Jean-Frédéric Colombel, Sven Almer, Curt Tysk, Sean Montague, Miquel Gassull, Steen Christensen, Yigael Finkel, Corinne Gower-Rousseau, R Modigliani, Habib Zouali, Suzanne Lesage, Mathias Chamaillard, Jeanne Macry, Gilles Thomas, Jean-Marc Victor & J Belaiche on behalf of and the GETAID
Crohn's disease (CD) is a complex genetic disorder for which aetiology is unknown. Recently, genetic factors for susceptibility have been described. Several genetic loci have been mapped and partially explain the familial aggregations of the disease. However, environmental factors may also contribute to these aggregations. We considered that if the role of non-genetic factors was negligible, CD patients would be randomly distributed in sibships with multiple affected siblings. On the other hand if there was a significant environmental contribution, the siblings would be affected non-randomly over exposure status. In order to test this hypothesis, we studied 102 sibships with two or more affected siblings. A statistical test, named Cluster of Affected Sibling Test or CAST, was developed, based on the exact calculation of the probability of observing a given number of clusters of affected siblings in multiplex families. The null hypothesis of a random distribution of affected siblings was rejected (P=0.005). The observed excess of affected sibling clusters indicates that birth order influences the disease status. Considering that an adjacent order of birth is a global estimate of environmental sharing, this observation strongly suggests that environmental factors contribute to the observed familial aggregations of the disease. This observation provides evidence that familial CD is a relevant tool for further studies of environmental factors and gene-environment interaction. More generally, the CAST statistics may be widely applicable to estimate the involvement of environmental factors in the aetiology of other binary traits which may be observed in multiple members of the same sibship.
A clustering of Crohn's disease in Mankato, Minnesota
H J Van Kruiningen, B J Freda
Infrequently, clusterings of Crohn's disease (CD) occur that suggest it is transmissible. We studied such a clustering. Graduates of the Mankato West High School Class of 1980 were contacted by mail and asked to respond, by self-addressed postcard, to a six-item questionnaire about inflammatory bowel disease and CD. Responses were followed-up by telephone contact and additional mailings. Two visits were made to Mankato, Minnesota, to interview individuals with CD, to obtain medical records, radiographs, and sera, and to study environmental risk factors. Of the 320 graduates of the class of 1980, 285 were contacted. Seven cases of CD were identified, the equivalent of a prevalence of 2,400/100,000. Concerns were discovered that CD may have emanated from recreational swimming. Fecal coliform counts in excess of 200/dL, the standard above which water is regarded as unsafe for recreational use, had been recorded year after year for the Blue Earth River at Mankato and for the Minnesota River. Recent fecal coliform counts (1993-1995) of Lake Washington, Lake German/Jefferson, and Lake Shetek were greater than 200/dL in 57%, 65%, and 62% of water samples. This clustering, in unrelated individuals, argues against a genetic cause for CD and suggests that environmental transmission occurred.
An in-depth study of Crohn's disease in two French families
H J Van Kruiningen 1 , J F Colombel, R W Cartun, R H Whitlock, M Koopmans, H O Kangro, J A Hoogkamp-Korstanje, M Lecomte-Houcke, M Devred, J C Paris, et al.
Abstract
Background: Two French families were investigated. In the first a husband, wife, and 4 children had Crohn's disease; in the second 7 of 11 children had the disease. There was no history of Crohn's disease in antecedent generations and no linkage to HLA haplotypes.
Methods: Methods included family interviews; review of medical records, radiographs, and pathology slides; serology; selective stool culture; enzyme-linked immunosorbent assay for fecal viral detection; and immunocytochemistry.
Results: In both families multiple cases occurred among siblings in 7-13-month periods. There appeared to be a 4-8-year recurrence of new disease in both families. Radiographs showed a remarkable similarity in the pattern of disease, confined to distal ileum and cecum, in the members of family 1. Examination for pathology showed granulomas in all 8 patients for whom tissues were available. Acid-fast organisms or Campylobacter-like organisms were not found in tissue sections, and immunocytochemistry was negative for mycobacteria and Yersinia. Stool cultures were negative for mycobacteria, Yersinia, and Mycoplasma. Torovirus and coronavirus antigens were not found in stool. Serology was negative for antibodies to Brucella, Yersinia, influenza, and three enteropathogenic viruses of animals.
Conclusions: The circumstances and data suggest that an infectious microorganism is responsible for these clusterings of Crohn's disease.
Clustering of Crohn's disease in a Cotswold village
R. N. ALLAN, P. PEASE, J. P. IBBOTSON
The first large cluster of patients with Crohn's disease, identified in the parish of Blockley, Gloucestershire is reported. Twelve patients with Crohn's disease have been identified of whom only two (a father and daughter) are known to be related. The age and sex distribution and macroscopic site of disease at diagnosis is similar to that expected in an unselected series. The identification of such a cluster suggests that environmental factors may be important in pathogenesis.
