KARACİĞER TRANSPLANTASYONUNDA MİKROKİMERİZM OLMADAN TOLERANS MÜMKÜN MÜDÜR?

Karaciğer transplantasyonu sonrası tolerans kavramı son yıllarda giderek popülarite kazanmaktadır. Bu çalışmada amacımız çok özenli parametrelerle seçilmiş yaklaşık on yıllık bir seride düşük doz immünosupressif kullanan bir grupta toleransın varlığını CD3+ hücrelerde mikrokimerizmin yokluğu ile kanıtlamaya çalışmaktır.Mikrokimerizm yokluğunu araştırma yöntemi; retrospektif olarak donör kanlarından cross match yapılarak DNA izolasyonunun ardından, mikrosatellit markerlarının PCR ile amplifikasyonu ve dönör ve alıcı allellerinin karşılaştırılması ilkesine dayanıyordu.Postoperatif takiplerinde organ reddi ya da buna bağlı komplikasyonları olmayan alkole bağlı sirozu olan 12 hastadan bir izogrup oluşturuldu. Bu hastalar immunsüpresif olarak takrolimus ve mikofenolat mofetil kullanıyordu ve ilaç kan düzeyleri 5 ng/l yani kabul edilebilir sınırın altında idi. Çalışmamızda hiçbir hastamızda kimerizm gözlemlemedik.Biyokimyasal stabiliteyi koruyan mikrokimerizmin yokluğu yani transplantasyona tolerans olması durumunda immunsupressif tedavilerin kesilebilir olmasının düşünülebilirliği gündeme gelmektedir.Böylelikle immünsüpressif tedavilerin yan etkileri azalacak ve hastalar böbrek yetmezliği, metabolik bozukluklar, diyabet ve kanserlerin artmış riskinden korunacak, dolayısı ile yaşam kalitesi artmış ve transplantasyon sonrası kullanılan ilaçların ülke ekonomisine yükü azalmış olacaktır.

TOLERANCE WITHOUT MICROCHIMERISM: IS THAT POSSIBLE IN LIVER TRANSPLANTATION?

It is uncovered the relationship between microchimerism and liver graft tolerance. Many studies inspired the concept of microchimerism and tolerance in solid organ transplantation (SOT). Our aim is to explore this aspect in a strictly selected patients’ cohort on CD3+ cells to show the microhimerism disappearance provethe tolerance instead of presence of it.We strictly selected liver transplantation patients treated with calcineurins inhibitors (cnis), with very low dose of drugs who has never developed documented rejection. The DNA extraction and microchimerism research method used was based on the discrimination of donor and recipient alleles by PCR amplification of microsatellite markers and capillary electrophoresis with fluorescence detection. Twelve patients with alcohol-induced cirrhosis without rejection or rejection-related complications during the post-operative course were selected. The immunosuppressive regimen included tacrolimus and mycophenolate mofetil. The blood residual tacrolimus concentration was under or equal 5 ng/L below normal.We described the count of white blood cells and selected CD3+ after the MACS separation procedure. In our study, we did not observe any microchimerismin none of the patients.We achieved that in case of absence of microchimerism with maintained biochemical stability we could choose to switch off the immunosuppressive therapy even the microchimerism accepted like a condition to the tolerance till our study. Consequently, it will be reduce the side effects of immunosuppressive treatmentsuch as renal failure, metabolic disorders, diabetes mellitus and cancers and the patient's quality of life will be improved be decreased financial aspect of immunesuppressive treathment.

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