Crohn's disease (CD), also known as regional ileitis, granulomatous enteritis, and segmental enteritis, is an inflammatory bowel disease (IBD) of unknown origin. Together with chronic nonspecific ulcerative colitis, these two diseases are collectively referred to as IBDs. Crohn's disease can occur anywhere in the gastrointestinal tract but most commonly affects the terminal ileum and the right colon. The main symptoms include abdominal pain, diarrhea, and intestinal obstruction, along with extraintestinal manifestations such as fever and nutritional disorders. The course of the disease is often prolonged, frequently recurring, and difficult to cure.
---
### One: Infection
Using specific DNA probes by PCR methods, Mycobacterium paratuberculosis (MP) was found in the tissues of 2/3 of CD patients; when tissue homogenates from CD were inoculated into golden hamsters, half developed granulomatous inflammation, with 40% being MP-PCR positive; measles virus inclusion bodies were found in CD tissues; under sterile conditions, experimental animals did not develop intestinal inflammation; additionally, metronidazole has shown some efficacy for CD. All of these findings suggest that infection may play a certain role in the onset of CD.
---
### Two: Immunity
Both humoral immunity and cellular immunity are abnormal in patients. More than half of the blood samples tested positive for colonic antibodies, circulating immune complexes (CIC), and elevated levels of complement C2 and C4. Using immunoenzyme labeling, antigen-antibody complexes and complement C3 were detected in diseased tissues. During cell culture, lymphocytes from patients exhibited toxicity and could kill normal colonic epithelial cells; after resection of the diseased bowel segment, this cytotoxic effect disappeared. Leukocyte migration inhibition tests showed abnormal responses, indicating a delayed hypersensitivity mediated by cellular immunity; tuberculin test reactions were low; and the dinitrochlorobenzene (DNCB) test was often negative, all supporting a low cellular immune function. Recently, it has been discovered that certain cytokines, such as IL-1, 2, 4, 6, 8, 10, interferon-gamma, and tumor necrosis factor-alpha, are associated with the onset of inflammatory bowel diseases. This suggests that the onset of CD may be related to immune abnormalities.
---
### Three: Genetics
The incidence of this disease shows significant racial differences and familial clustering. In terms of incidence, Caucasians have a higher rate than blacks, and monozygotic twins have a higher rate than dizygotic twins; 10%-15% of CD patients have a family history; studies have found that there are certain genetic defects associated with this disease. These findings suggest a genetic predisposition for the disease.
Previous research has proven the relationship between a mutation in a gene on chromosome 16 and Crohn's disease. Recent articles have identified this gene as NOD2, which plays a role in bacterial-triggered inflammatory responses. Clinically, antibiotics are used to treat some cases of Crohn's disease. In the laboratory, inflammatory bowel disease (IBD) animal models prepared under sterile conditions often do not exhibit IBD. Therefore, the NOD2 gene is an excellent candidate as a susceptibility gene for Crohn's disease and an important common pathogenic factor associated with the onset of Crohn's disease, immune response, and the role of gut bacteria.