Publication: Böbrek transplantasyonunda Fc-y ve toll benzeri reseptör ekspresyonlarının immün yanıtta rolü
Abstract
1.ÖZET Bu çalışmada Kronik Böbrek yetmezliği (KBY) olan hastalarda böbrek transplantasyonu öncesi ve sonrası Toll-benzeri reseptörlerin ve Fc-γ reseptörlerinin transplantasyon öncesi sonrası immün hücrelerde yüzey ekspresyon düzeylerinin belirlenmesi ve bu yüzey belirteçlerinin, immünolojik reddin hücresel düzeyde erken saptanabilmesinde kullanılıp kullanılamayacağının incelenmesi amaçlanmıştır. Kırkbir KBY hastasının nakil öncesi ve nakil sonrası monosit(CD14+), dendritik hücre (CD209+), lenfosit(CD45+CD14-) ve granülositlerinde, Fc-γRI, RIIa ve b;RIII ve Toll benzeri reseptörlerden TLR2 ve TLR4 ekspresyonları incelendi. Ek olarak aktivasyon belirteçlerinden, CD80, CD86 ve HLA-DR de adı geçen hücre populasyonlarında değerlendirildi. Monosit ve granülosit populasyonlarında, nakil sonrasında FcγRIII ekpresyonlarının anlamlı düzeyde azaldığı, monosit populasyonunda ise FcγRI ekpresyonunda anlamlı bir artış olduğu belirlenmiştir. Tüm diğer Fc reseptörlerde, TLR’lerde de oran ve ortalama fluoresan yoğunluğu (MFI) olarak azalma olmasına rağmen bu fark anlamlılık seviyesine ulaşmamıştır. Kostimülatör moleküllerin ekspresyonları karşılaştırıldığında CD86 ekpresyonunda bir değişim saptanmazken, CD80 ekpresyonunun nakil sonrası anlamlı düzeyde azaldığı belirlenmiştir. (p<0.05). HLA-DR ekspresyonunun incelemesinde, lenfosit populasyonu üzerinde nakil sonrasında iki katına yakın bir artış saptanmıştır. Bu çalışmada tüm hücre gruplarında azalma gösteren FcγR III ve lenfosit populasyonunda artan HLA-DR red takibi konusunda umut verici göstergeler olabilir. Reseptörler, allograft reddi, TLR, HLA-DR 2.
The Role of FcγRs, TLR2 and TLR4 Associated Immune Response in Chronic Renal Failure The most effective treatment of patients with Chronic renal failure (CRF) is organ transplantation. Success of organ transplantation depends on the immunological compatibility between donor and host. However, limited number of pre-transplantation tests are obviously not enough for the prediction of uncoming rejection reactions. In this study, we assessed molecular expression features of all white blood cells by using a broad panel including Fc receptors and Toll Like Receptors in patients with CRF at pre and post transplantation states. When we compared FcγRIII and TLRs expressions on monocytes, we determined that after transplantation FcγRIII (CD16) expression was significantly decreased (p<0,01). When we assessed the mean fluorescence intensity of molecules on cell membrans of monocytes, the mean fluorescence intensity of FcRIII (CD16) had a significant decrease in all patients after transplantation (p<0,05). In comparison of costimulator molecules, a decreased expression for CD80 has been found after transplantation (p<0,01). Although no percentage change has been found of CD86, a decreased in the mean fluorescence intensityof CD86 has been shown in post transplant patients (p<0,05). When we assessed FcγRs, TLR2 and TLR4 expressions on granulocytes, no signiticant changes has been found. Tendency of decreasing of mean fluorescence intensity of CD16 has also been found on granulocytes (p<0,05). We also detected that CD64 and TLR4 has decreased after transplantation (p<0,05). Analysis of lymphocyte showed that a significant decrease in CD8+CD28- cell populations after transplantation ( 11,3%±6,8 , 7,2%±-6,4; p<0,01).Additionally, that HLA-DR expression on B cells was increased has been found. We conclude that decrease expression of CD16 on all white blood cells and increased expression of HLA-DR might use in transplantation monitoring. However, longutidunal studies including clinical data from patients under long term follow-ups are needed. Key Words: Fc-γ receptors, allograft rejection, TLRs, HLA-DR
The Role of FcγRs, TLR2 and TLR4 Associated Immune Response in Chronic Renal Failure The most effective treatment of patients with Chronic renal failure (CRF) is organ transplantation. Success of organ transplantation depends on the immunological compatibility between donor and host. However, limited number of pre-transplantation tests are obviously not enough for the prediction of uncoming rejection reactions. In this study, we assessed molecular expression features of all white blood cells by using a broad panel including Fc receptors and Toll Like Receptors in patients with CRF at pre and post transplantation states. When we compared FcγRIII and TLRs expressions on monocytes, we determined that after transplantation FcγRIII (CD16) expression was significantly decreased (p<0,01). When we assessed the mean fluorescence intensity of molecules on cell membrans of monocytes, the mean fluorescence intensity of FcRIII (CD16) had a significant decrease in all patients after transplantation (p<0,05). In comparison of costimulator molecules, a decreased expression for CD80 has been found after transplantation (p<0,01). Although no percentage change has been found of CD86, a decreased in the mean fluorescence intensityof CD86 has been shown in post transplant patients (p<0,05). When we assessed FcγRs, TLR2 and TLR4 expressions on granulocytes, no signiticant changes has been found. Tendency of decreasing of mean fluorescence intensity of CD16 has also been found on granulocytes (p<0,05). We also detected that CD64 and TLR4 has decreased after transplantation (p<0,05). Analysis of lymphocyte showed that a significant decrease in CD8+CD28- cell populations after transplantation ( 11,3%±6,8 , 7,2%±-6,4; p<0,01).Additionally, that HLA-DR expression on B cells was increased has been found. We conclude that decrease expression of CD16 on all white blood cells and increased expression of HLA-DR might use in transplantation monitoring. However, longutidunal studies including clinical data from patients under long term follow-ups are needed. Key Words: Fc-γ receptors, allograft rejection, TLRs, HLA-DR