Abstract
Because of a mutation of the gene allowing the synthesis of the Neu5Gc form of neuraminidic acid, humans lack the Neu5Gc present in other mammals and develop anti-Neu5Gc. However, humans can absorb dietary Neu5Gc and normal colon epithelium displays minute amounts of Neu5Gc. The potential “physiological” formation of in situ immune complexes has been proposed as a risk factor for colon cancer and as the link between red meat-rich diet and colon carcinoma. In this article, we took advantage of evidence that polyclonal rabbit IgG (ATG) elicits an immune response against Neu5Gc and we consulted a large data base of allograft recipients treated or not with animal-derived IgG to discuss this hypothesis. Based on data from 173,960 and 38,505 patients without and with ATG induction, respectively, we found no evidence that exposure to higher levels of anti-Neu5Gc is associated with a higher incidence of colon carcinoma.
Highlights
Centre de Recherche en Transplantation et Immunologie UMR 1064, INSERM, Université de Nantes, Institut de Transplantation Urologie Néphrologie (ITUN), CHU Nantes, 44093 Nantes, France
Whereas evolution has likely censured possible deleterious effects of the diet-derived anti-Neu5Gc antibody, animal-derived tissues such as engineered pig skin for severe burns [8] or molecules such as rabbit anti-thymocyte globulin (ATG), which contain Neu5Gc in mass spectrometry analysis [9], are able to trigger a vigorous memory-like rise of anti-Neu5Gc antibodies [10], in addition to antibodies directed at the IgG protein backbone or at other sugar such as α1,3Gal
We took advantage of the two key variables precisely documented in a large population of more than 200,000 kidney transplant recipients as part of the Collaborative Transplant Study (CTS) [21], namely (i) the absence or presence of post transplantation induction therapy with rabbit ATG and (ii) the absence or presence of a colon cancer, to analyze a possible link between anti-Neu5Gc exposure and colon cancer
Summary
Centre de Recherche en Transplantation et Immunologie UMR 1064, INSERM, Université de Nantes, Institut de Transplantation Urologie Néphrologie (ITUN), CHU Nantes, 44093 Nantes, France. Induction, patients who received rabbit ATG during the first weeks following kidney transplantation have been shown to develop anti-Neu5Gc antibodies that circulate for months or years in the blood [9].
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