Ibd Pathogenesis

INTRODUCTION

The inflammatory bowel diseases (IBD), Crohn’s disease (CD) and ulcerative colitis (UC), affect a large number of Europeans [1, 2]. Despite the introduction of new treatments, CD and UC remain chronic conditions with severe disease morbidity, often complicated by surgery and frequent admissions to hospital [1, 3].

Although studies of the genome have found 200 loci associated with IBD, the variation in the IBD phenotype explained by these finding is still below 25-30% [4, 5] suggesting a role of environmental factors in IBD pathogenesis. Several studies indicate environmental impact on IBD pathogenesis including; exposure to pathogens [6], disease associated dysbiosis [7], metabolic disequilibrium [8], or epigenetic modifications

Cohort recruitment

Merging the Danish Twin Register and the National Patient Register, identified 159 MZ twin pairs in which at least one twin had a diagnosis of either CD or UC according to the National Patient Register as of May 1st 2013. Of these, 113 index twins (the first twin to contract IBD according to the register) responded to the invitational letter of whom 42 twins declined to participate. Of the 71 positive index twin responders, nine co-twins did not wish to participate, leaving 62 pairs for inclusion, Figure 1.

Data collection

The participants filled out a questionnaire including age, sex, smoking status, medication, dietary patterns including a food frequency questionnaire, a 48-hour dietary recall, time of last meal or exercise, travel history, and pregnancies and disease activity at time of sampling, either Harvey Bradshaw Index (CD) (33) or Simple Clinical Colitis Index (UC)

Histopathology consistent with Crohn’s disease (epitheloid granuloma of Langerhans type or transmural discontinuous focal or patchy inflammation)

4. Fistula and/or abscess in relation to affected bowel segments.

Copenhagen Diagnostic Criteria for UC (all three of the criteria present) [26, 28]:

1. History of diarrhoea and/or rectal bleeding and pus for more than one week or repeated episodes

2. Characteristic endoscopic findings of continuous ulceration, vulnerability or granulated mucosa

3. Histopathology consistent with ulcerative colitis (neutrophils within epithelial structures, cryptitis, crypt distortion, crypt abscesses).

Inter-observer variation has previously been found with regards to the Montreal classification [29]. To avoid potential inter-observer variation one researcher validated the diagnoses and assessed the Montreal classification (FTM). Furthermore, to improve validity of diagnoses and phenotypes, complicated cases were reviewed by a gastroenterological specialist and senior physician (VAN). In daily clinical practice, the diagnosis may remain difficult; therefore, we included cases, which were perceived to have IBD by the treating physician although not fulfilling the Copenhagen criteria as IBD cases according to available information from the files. Cases where the diagnosis of IBD was unlikely were designated “Gastrointestinal (GI) symptoms not IBD” for future