BACKGROUND The aim of this study was to investigate whether the number of transplantations, as a marker of the graft rejection status of the patient, is associated with an increased risk of... Show moreBACKGROUND The aim of this study was to investigate whether the number of transplantations, as a marker of the graft rejection status of the patient, is associated with an increased risk of malignancies. METHODS In a cohort study, 1213 patients, receiving a kidney transplantation between 1966 and 1995 at the Leiden University Medical Center, were analyzed. All cutaneous squamous cell carcinoma and internal malignancies, which had developed between 1966 and 2007, were recorded. The influence of number of transplantations, age, sex and time on immunosuppression on the risk of squamous cell carcinoma and internal malignancies was investigated by time-dependent multivariate Cox's proportional hazard models. RESULTS Of the 1213 kidney transplant recipients, 319 received a second kidney, 78 a third; 13 of them a fourth and 4 of them a fifth transplantation. After adjustment for potentially confounding factors, including age, sex and years on immunosuppressive therapy we did not detect an increased risk of cancer in patients with multiple transplantations. On the contrary, patients with three or more transplantations had a 1.6-fold decreased risk of squamous cell carcinomas and a 3.6-fold decreased risk of internal malignancies. CONCLUSION We conclude that kidney transplant recipients with three or more transplantations do not have an increased risk of cutaneous squamous cell carcinoma and internal malignancies. Show less
Pol, P. van der; Vries, D.K. de; Gijlswijk, D.J. van; Anken, G.E. van; Schlagwein, N.; Daha, M.R.; ... ; Kooten, C. van 2012
In egg donation (ED) pregnancies the fetus is allogeneic to the gestational carrier. During these ED pregnancies the mother has to cope with a higher degree of antigenic dissimilarity compared with... Show moreIn egg donation (ED) pregnancies the fetus is allogeneic to the gestational carrier. During these ED pregnancies the mother has to cope with a higher degree of antigenic dissimilarity compared with spontaneously conceived pregnancies. At the fetal-maternal interface maternal cells and fetal cells come in close contact. Understanding the immune mechanisms at this fetal-maternal interface gives more insight into the question why the (semi-)allogeneic fetus is accepted and not rejected by the mother. The degree of antigenic dissimilarity in ED pregnancies is comparable with that in solid organ transplantations with HLA mismatched unrelated donors. Therefore, the immunologic interactions between mother and child in successful ED pregnancies may be relevant for the induction of immunological tolerance in solid organ transplantation. Show less
Hoorn, M.L.P. van der; Scherjon, S.A.; Claas, F.H.J. 2011
The mechanisms by which alloreactive memory T-cells are generated in non-sensitized individuals have begun to be elucidated. It is generally accepted that a very high level of crossreactivity is an... Show moreThe mechanisms by which alloreactive memory T-cells are generated in non-sensitized individuals have begun to be elucidated. It is generally accepted that a very high level of crossreactivity is an essential feature of the T-cell receptor. Indeed it has recently been shown that alloreactivity from viral specific memory T-cells is far more common than predicted, 45% of viral specific T-cell clones were found to be allo-HLA crossreactive. In this overview the evidence for crossreactive alloresponses from human viral specific memory T-cells is discussed with special emphasis on the unexpected high frequency of these crossreactive responses, the peptide and tissue specificity of the responses, and the mechanistic insights gleaned from the elucidation of the crystal structure of an allo-HLA crossreactive viral specific TCR. The possible implications for clinical solid organ and bone marrow transplantation and tolerance induction will be discussed. Show less
The mechanisms by which alloreactive memory T-cells are generated in non-sensitized individuals have begun to be elucidated. It is generally accepted that a very high level of crossreactivity is an... Show moreThe mechanisms by which alloreactive memory T-cells are generated in non-sensitized individuals have begun to be elucidated. It is generally accepted that a very high level of crossreactivity is an essential feature of the T-cell receptor. Indeed it has recently been shown that alloreactivity from viral specific memory T-cells is far more common than predicted, 45% of viral specific T-cell clones were found to be allo-HLA crossreactive. In this overview the evidence for crossreactive alloresponses from human viral specific memory T-cells is discussed with special emphasis on the unexpected high frequency of these crossreactive responses, the peptide and tissue specificity of the responses, and the mechanistic insights gleaned from the elucidation of the crystal structure of an allo-HLA crossreactive viral specific TCR. The possible implications for clinical solid organ and bone marrow transplantation and tolerance induction will be discussed. (C) 2010 Elsevier B.V. All rights reserved. Show less
