<strong>Background:</strong> Ischemia-reperfusion injury of organ transplantation activates several mediators which may link the innate to the adaptive immune response. Down the cascade of TLRs, we selecte...<strong>Background:</strong> Ischemia-reperfusion injury of organ transplantation activates several mediators which may link the innate to the adaptive immune response. Down the cascade of TLRs, we selected to study the expression of Interferon Regulatory Factors (IRF)-3 and -7 inside human Kidney Transplanted (KTx) organs and the synthesis of IFN<i>α</i>, the main growth factor induced by them, in KTx aspiration biopsy cultures. Simultaneously, we tested their robustness in diagnosing Acute Rejection (AR). <strong>Methods:</strong> Fine-needle aspiration biopsies (F-nab) were performed either on day 7 or 14 post-KTx among stable patients or on the day of AR diagnosis. On Fnab cytopreparations, we studied IRF3 and IRF7 by the enzymatic avidin-biotin complex staining, and in a different group of cases we quantified IFN<i>α</i> by ELISA in 48 hours Fnab culture supernatants. <strong>Results:</strong> AR group showed a significantly up-regulated expression for IRF3 and IRF7, reaching Positive Predictive Values (PPV) of 0.824 and 0.8, respectively, as well as Negative Predictive Values (NPV) above 0.9 for both;IFN<i>α</i> presented a PPV = 1.0 and a NPV = 0.9. A variation in the results was noticed according to different immunosuppressive therapies. <strong>Conclusions:</strong> Our findings suggest that IRF3 and IRF7, and IFN<i>α</i> which they promote, may be very important players in the early days post-KTx, linking the innate with an adaptive response and triggering acute rejection. These differences were very clear-cut, lending consistency to our speculation. It would be important to scrutinize for other potential effects derived from these IRFs up-regulation which could be of clinical relevance.展开更多
<p style="text-align:justify;"> <span>Following organ transplantation</span><span>,</span><span> the outcome of the encounter between an APC and a T lymphocyte is str...<p style="text-align:justify;"> <span>Following organ transplantation</span><span>,</span><span> the outcome of the encounter between an APC and a T lymphocyte is strongly dependent on the presence of costimulatory and co-inhibitory molecules, the former associated with allograft rejection and the latter with allograft acceptance. We evaluated the expression of PD-L2, GITR, ILT-2/3/5, and ILT-4 on graft-infiltrating cells procured by Fnab from human KTx under different immunosuppressive regimens. Methods: Fnab biopsies were performed on days 7 or 14</span><span> </span><span>-</span><span> </span><span>30 in stable KTx and on the day of acute rejection diagnosis. Cytopreparations were studied by the enzymatic avidin biotin complex staining. Results: Acute rejection group </span><span>showed a significant down-regulated expression of PD-L2, GITR, and ILT-2/3/5 </span><span>as compared to stable group, while for ILT-4 we did not find significant difference. Anti-IL2</span><i><span>α</span></i><span>R and rapamicyn treatment trend to down-regulate ILT-4 expression, although meaningless. A significant</span><span>ly</span><span> positive correlation was observed between PD-L2 and GITR expression in Fnab. The PPV for acute rejection diagnosis for both PD-L2 and GITR w</span><span>as</span><span> clearly above 0.8. Conclusions: Our findings point to an early entrance of cells expressing PD-L2, GITR and ILT-2/3/5 inside human KTx who are going to remain rejection-free. Both PD-L2 and GITR shared a high ability to rule-in and rule-out acute rejection.</span> </p>展开更多
Background: We studied the expression of important costimulatory molecules of lymphocyte activation and the presence of CD16<sup><span style="font-family:Verdana;vertical-align:super;">+</span...Background: We studied the expression of important costimulatory molecules of lymphocyte activation and the presence of CD16<sup><span style="font-family:Verdana;vertical-align:super;">+</span></sup><span style="font-family:Verdana;"> cells on aspiration biopsies of kidney transplants, measured three soluble factors and whe</span><span style="font-family:Verdana;">n indicated tested their robustness in diagnosing acute rejection.</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">Methods</span><span style="font-family:Verdana;">: Fine-needle aspiration biopsies were performed either on days seven or 14</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">-</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">30 post-transplantation among stable kidney transplants and on the day of acute rejection diagnosis, while a sample of peripheral blood was collected simultaneously. The cyto</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">preparations were studied by the enzymatic </span><span style="font-family:Verdana;">avidin biotin complex staining. The immunocytochemistry was directed to CD16, CD28, CD152, ICOS, CD40, CD154, CD26 and CD27. We performed the analysis in the peripheral blood by ELISA for soluble(s) CD16, CD26, and CD154.</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">Results: The group of acute rejection cases showed a significant up-regulated expression of CD16, CD26, ICOS and CD40 as compared to the group of stable cases. Both sCD16 and sCD154 were significantly higher in the blood samples of the group with acute rejection. Thymoglobulin down-regulated CD154 and sCD16. CD16, CD26 and ICOS exhibited very high sensitivity and specificity for acute rejection diagnosis.</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">Conclusions: The presence of CD16</span><sup><span style="font-family:Verdana;vertical-align展开更多
文摘<strong>Background:</strong> Ischemia-reperfusion injury of organ transplantation activates several mediators which may link the innate to the adaptive immune response. Down the cascade of TLRs, we selected to study the expression of Interferon Regulatory Factors (IRF)-3 and -7 inside human Kidney Transplanted (KTx) organs and the synthesis of IFN<i>α</i>, the main growth factor induced by them, in KTx aspiration biopsy cultures. Simultaneously, we tested their robustness in diagnosing Acute Rejection (AR). <strong>Methods:</strong> Fine-needle aspiration biopsies (F-nab) were performed either on day 7 or 14 post-KTx among stable patients or on the day of AR diagnosis. On Fnab cytopreparations, we studied IRF3 and IRF7 by the enzymatic avidin-biotin complex staining, and in a different group of cases we quantified IFN<i>α</i> by ELISA in 48 hours Fnab culture supernatants. <strong>Results:</strong> AR group showed a significantly up-regulated expression for IRF3 and IRF7, reaching Positive Predictive Values (PPV) of 0.824 and 0.8, respectively, as well as Negative Predictive Values (NPV) above 0.9 for both;IFN<i>α</i> presented a PPV = 1.0 and a NPV = 0.9. A variation in the results was noticed according to different immunosuppressive therapies. <strong>Conclusions:</strong> Our findings suggest that IRF3 and IRF7, and IFN<i>α</i> which they promote, may be very important players in the early days post-KTx, linking the innate with an adaptive response and triggering acute rejection. These differences were very clear-cut, lending consistency to our speculation. It would be important to scrutinize for other potential effects derived from these IRFs up-regulation which could be of clinical relevance.
文摘<p style="text-align:justify;"> <span>Following organ transplantation</span><span>,</span><span> the outcome of the encounter between an APC and a T lymphocyte is strongly dependent on the presence of costimulatory and co-inhibitory molecules, the former associated with allograft rejection and the latter with allograft acceptance. We evaluated the expression of PD-L2, GITR, ILT-2/3/5, and ILT-4 on graft-infiltrating cells procured by Fnab from human KTx under different immunosuppressive regimens. Methods: Fnab biopsies were performed on days 7 or 14</span><span> </span><span>-</span><span> </span><span>30 in stable KTx and on the day of acute rejection diagnosis. Cytopreparations were studied by the enzymatic avidin biotin complex staining. Results: Acute rejection group </span><span>showed a significant down-regulated expression of PD-L2, GITR, and ILT-2/3/5 </span><span>as compared to stable group, while for ILT-4 we did not find significant difference. Anti-IL2</span><i><span>α</span></i><span>R and rapamicyn treatment trend to down-regulate ILT-4 expression, although meaningless. A significant</span><span>ly</span><span> positive correlation was observed between PD-L2 and GITR expression in Fnab. The PPV for acute rejection diagnosis for both PD-L2 and GITR w</span><span>as</span><span> clearly above 0.8. Conclusions: Our findings point to an early entrance of cells expressing PD-L2, GITR and ILT-2/3/5 inside human KTx who are going to remain rejection-free. Both PD-L2 and GITR shared a high ability to rule-in and rule-out acute rejection.</span> </p>
文摘Background: We studied the expression of important costimulatory molecules of lymphocyte activation and the presence of CD16<sup><span style="font-family:Verdana;vertical-align:super;">+</span></sup><span style="font-family:Verdana;"> cells on aspiration biopsies of kidney transplants, measured three soluble factors and whe</span><span style="font-family:Verdana;">n indicated tested their robustness in diagnosing acute rejection.</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">Methods</span><span style="font-family:Verdana;">: Fine-needle aspiration biopsies were performed either on days seven or 14</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">-</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">30 post-transplantation among stable kidney transplants and on the day of acute rejection diagnosis, while a sample of peripheral blood was collected simultaneously. The cyto</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">preparations were studied by the enzymatic </span><span style="font-family:Verdana;">avidin biotin complex staining. The immunocytochemistry was directed to CD16, CD28, CD152, ICOS, CD40, CD154, CD26 and CD27. We performed the analysis in the peripheral blood by ELISA for soluble(s) CD16, CD26, and CD154.</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">Results: The group of acute rejection cases showed a significant up-regulated expression of CD16, CD26, ICOS and CD40 as compared to the group of stable cases. Both sCD16 and sCD154 were significantly higher in the blood samples of the group with acute rejection. Thymoglobulin down-regulated CD154 and sCD16. CD16, CD26 and ICOS exhibited very high sensitivity and specificity for acute rejection diagnosis.</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">Conclusions: The presence of CD16</span><sup><span style="font-family:Verdana;vertical-align
