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We read with interest the stimulating case report on fulminant Crohn’s colitis following allogenic stem cell transplantation by
and the respective editorial.1 The authors and the editorialists hypothesised on whether the colitis might be ascribed to the adoptive transfer of stem cells displaying genetic alterations which are associated with Crohn’s disease. However, the ileal sparing disease localisation and course of the colitis which finally necessitated urgent colectomy is rather unusual for Crohn’s colitis. In addition, the genetic mismatch between donor and recipient is hardly compatible with the outlined hypothesis.
According to the cited study by Lesage and colleagues,2 the allele difference at position −33 of the 5′ UTR polymorphism of the NOD2 gene is not regarded as “a disease causing mutation”. In line with this concept is the fact that the donor and his first degree relatives did not suffer from Crohn’s disease. Apart from this observation, the authors did not describe in detail which particular genetic mutations or polymorphisms differed between the donor and recipient. However, some of the described genes are simply not associated with inflammatory bowel disease. As shown by some of the authors3 and ourselves,4 polymorphisms in the MICB gene (which is not situated within the HLA class III but the HLA class I region) are not associated with Crohn’s disease. The same holds true for polymorphisms of the HSP70 gene which were weakly associated with a more severe course of Crohn’s disease in Japanese patients but not with the disease itself.5 To the best of our knowledge, data on possible associations between mutations of the LMP2, LMP7, and NOTCH4 gene and Crohn’s disease are completely lacking. In conclusion, at best only an extremely weak genetic predisposition can be extracted from the extensive genotyping and thus the postulated transfer of genetic susceptibility remains highly speculative.
The increased incidence of inflammatory bowel disease in patients with congenital immune defects and the recently described increased adherence of bacteria at the intestinal mucosa, which might particularly be facilitated in the presence of mutated NOD2 protein, suggest that the initial event in the complex pathophysiological process in Crohn’s disease is compatible with impaired mucosal clearing function which precedes an excessive largely T cell driven immunological activity. This hypothesis is further sustained by various genetically engineered animal models which are protected from the development of enterocolitis under germ free conditions, and therapeutic approaches, such as the use of immunostimulatory substances or antibiotic therapy (for overview see Folwaczny and colleagues6). Thus a complementary explanation for the described phenomenon might be the persistent immunosuppressive therapy the donor had received.
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