TY - JOUR
T1 - Cytokine gene polymorphisms and acute human liver graft rejection
AU - Warlé, Michiel C.
AU - Farhan, Ayar
AU - Metselaar, Herold J.
AU - Hop, Wim C J
AU - Perrey, Chris
AU - Zondervan, Pieter E.
AU - Kap, Marcel
AU - De Rave, Sjoerd
AU - Kwekkeboom, Jaap
AU - IJzermans, Jan N M
AU - Tilanus, Hugo W.
AU - Pravica, Vera
AU - Hutchinson, Ian V.
AU - Bouma, Gerda J.
PY - 2002
Y1 - 2002
N2 - Interindividual differences exist in the capacity to produce cytokines. It has been reported that levels of in vitro cytokine production measured after stimulated cell culture are associated with polymorphisms in cytokine genes. Moreover, a correlation between heart, kidney, liver, and lung graft rejection or survival with cytokine gene polymorphisms has been described. In the present study, we analyzed the association of gene polymorphisms in T helper subtype 1 (TH1-), TH2-, and regulatory-type cytokines with human liver allograft rejection. Patients who received a primary liver graft from 1992 onward and were seen at the transplant outpatient clinic since then were included on this study (n = 89). Patients were HLA typed routinely. Biopsy-proven acute rejection occurred in 41 of 89 patients. After informed consent, blood was collected and DNA was obtained. Using amplification-refractory mutation system polymerase chain reaction, the following cytokine gene polymorphisms were determined: IL-2+166, IL-2-330, IL-15+13689, IL-15-80, TNF-A-308, TNFd3, IFN-G+874 (TH1-type cytokines), IL-4+33, IL-4-590, IL-6-174, IL-10-592, IL-10-819, IL-10-1082, IL-13+2043, IL-13-1055 (TH2 type cytokines), TGF-B1+869, and TGF-B1+915 (regulatory-type cytokines). Univariate analysis showed that polymorphisms of IL-10-1082, TGF-B1+869, and HLA-DR6 were significantly related to liver graft rejection. Multiple logistic regression analysis was used to assess which variables remained significantly predictive of acute rejection. Multivariate analysis showed that TGF-B1+869 and HLA-DR6 were independently associated with the occurrence of acute rejection. These findings suggest a role for the regulatory-type cytokine transforming growth factor-β1 in human liver graft rejection.
AB - Interindividual differences exist in the capacity to produce cytokines. It has been reported that levels of in vitro cytokine production measured after stimulated cell culture are associated with polymorphisms in cytokine genes. Moreover, a correlation between heart, kidney, liver, and lung graft rejection or survival with cytokine gene polymorphisms has been described. In the present study, we analyzed the association of gene polymorphisms in T helper subtype 1 (TH1-), TH2-, and regulatory-type cytokines with human liver allograft rejection. Patients who received a primary liver graft from 1992 onward and were seen at the transplant outpatient clinic since then were included on this study (n = 89). Patients were HLA typed routinely. Biopsy-proven acute rejection occurred in 41 of 89 patients. After informed consent, blood was collected and DNA was obtained. Using amplification-refractory mutation system polymerase chain reaction, the following cytokine gene polymorphisms were determined: IL-2+166, IL-2-330, IL-15+13689, IL-15-80, TNF-A-308, TNFd3, IFN-G+874 (TH1-type cytokines), IL-4+33, IL-4-590, IL-6-174, IL-10-592, IL-10-819, IL-10-1082, IL-13+2043, IL-13-1055 (TH2 type cytokines), TGF-B1+869, and TGF-B1+915 (regulatory-type cytokines). Univariate analysis showed that polymorphisms of IL-10-1082, TGF-B1+869, and HLA-DR6 were significantly related to liver graft rejection. Multiple logistic regression analysis was used to assess which variables remained significantly predictive of acute rejection. Multivariate analysis showed that TGF-B1+869 and HLA-DR6 were independently associated with the occurrence of acute rejection. These findings suggest a role for the regulatory-type cytokine transforming growth factor-β1 in human liver graft rejection.
U2 - 10.1053/jlts.2002.33967
DO - 10.1053/jlts.2002.33967
M3 - Article
C2 - 12089714
SN - 1527-6473
VL - 8
SP - 603
EP - 611
JO - Liver Transplantation
JF - Liver Transplantation
IS - 7
ER -
