DIFFERENT INTESTINAL PERMEABILITY PATTERNS IN RELATIVES AND SPOUSES OF PATIENTS WITH CROHN’S DISEASE: AN INHERITED DEFECT IN MUCOSAL DEFENCE?
J D Söderholm, G Olaison, E Lindberg, U Hannestad, A Vindels, C Tysk, G Järnerot, R Sjödahl. Gut 1999;44:96–100

Background—A familial defect in intestinal barrier function has been found in Crohn’s disease.
Aim—To investigate possible genetic and environmental influences on this barrier defect by studying intestinal permeability in both relatives and spouses of patients with Crohn’s disease.
Subjects—The study included 39 patients with Crohn’s disease, 34 healthy first degree relatives, and 22 spouses. Twenty nine healthy volunteers served as controls.
Methods—Intestinal permeability was assessed as the lactulose:mannitol ratio in five hour urinary excretion after oral load, both before (baseline) and after ingestion of acetylsalicylic acid. The permeability response represents the difference between the two tests. A ratio above the 95th percentile for controls was classified as abnormal.
Results—Baseline permeability was higher in patients and spouses than in controls. An abnormal baseline permeability was seen in 36% of the patients, 23% of the spouses, 18% of the relatives, and 3% of the controls.  After ingestion of acetylsalicylic acid, permeability increased significantly in all groups. Relatives were similar to patients with regard to permeability after exposure to acetylsalicylic acid, whereas spouses were similar to controls. The proportions with an abnormal permeability response to acetylsalicylic acid were 32% in patients, 14% in spouses, 41% in relatives, and 3% in controls.
Conclusion—The findings suggest that baseline permeability is determined by environmental factors, whereas permeability provoked by acetylsalicylic acid is a function of the genetically determined state of the mucosal barrier, and support the notion that environmental and hereditary factors interact in the pathogenesis of Crohn’s disease.
 

EARLY LESIONS OF RECURRENT CROHN’S DISEASE CAUSED BY INFUSION OF
INTESTINAL CONTENTS IN EXCLUDED ILEUM
DHaens GR; Geboes K; Peeters M; Baert F; Penninckx F; Rutgeerts P; Department of Internal
Medicine, University Hospital Gasthuisberg, Leuven, Belgium.  Gastroenterology, 1998 Feb, 114:2,
262-7

BACKGROUND & AIMS: Postoperative recurrence of Crohn’s disease may be triggered by
agents in the fecal stream. The aim of this study was to examine intestinal mucosal inflammation
induced by contact with intestinal fluids in surgically excluded ileum. METHODS: The effects of
infusion of intestinal luminal contents into excluded ileum in 3 patients with Crohn’s disease who had
undergone a curative ileocolonic resection with ileocolonic anastomosis and temporary protective
proximal loop ileostomy were studied by histopathology and electron microscopy. RESULTS:
Contact with intestinal fluids for 8 days induced focal infiltration of mononuclear cells, eosinophils, and polymorphonuclear cells in the lamina propria, small vessels, and epithelium in the excluded neoterminal ileum that was previously normal. CONCLUSIONS: Intestinal contents trigger postoperative recurrence of Crohn’s disease in the terminal ileum proximal to the ileocolonic anastomosis in the first days after surgery.
 

DIFFERENCES IN RISK OF CROHN’S DISEASE IN OFFSPRING OF MOTHERS AND FATHERS WITH INFLAMMATORY BOWEL DISEASE.
Akolkar PN; Gulwani Akolkar B; Heresbach D; Lin XY; Fisher S; Katz S; Silver J
Department of Medicine, North Shore University Hospital/Cornell University Medical College,
Manhasset, New York 11030, USA.   Am J Gastroenterol, 1997 Dec, 92:12, 2241-4

OBJECTIVE: To determine whether there are any unusual patterns of transmission of susceptibility
to inflammatory bowel disease (IBD) within multiplex families. METHODS: Individuals with IBD
were recruited for genome-wide screening of susceptibility genes. The extent of familial aggregation
and blood relationships in multiplex families were determined by questionnaires given to participants
followed up by confirmation of disease diagnosis by participants’ physicians. RESULTS: Of 135
families identified in which both a parent and a child had IBD, 93 involved transmission of
susceptibility to disease from mother to child versus 42 examples of transmission from father to child (p = 0.00001, exact two-tailed binomial test). This distortion in transmission on the basis of the sex of the parent was observed only among non-Jewish pairs with Crohn’s disease (CD), in which, of 33 parent-child pairs with CD, disease susceptibility was transmitted from the mother 28 times (p = 0.00007). CONCLUSION: Susceptibility to CD in a subset of patients may involve a gene that is imprinted.
 
NOTE: the authors' speculation that preferential transmission of CD "susceptibility" from mothers versus fathers is due to genetic factors is as possible as our belief that it is due to environmental influence: mothers on an average spend more time with children and prepare them meals than fathers, increasing the probability of transmission of an infectious agent.
 

AN IN-DEPTH STUDY OF CROHN’S DISEASE IN TWO FRENCH FAMILIES
HJ Van Kruiningen, JF Colombel, RW Cartun, RH Whitlock, M Koopmans, HO Kangro, JA
Hoogkamp-Korstanje, M Lecomte-Houcke, M Devred and JC Paris;  Department of Pathobiology, University of Connecticut, Storrs. Gastroenterology, Vol 104, 351-360, 1993

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.