Böbrek Naklinde Geleneksel HLA Uyumsuzluğuna Alternatif Bir Yaklaşım: HLA Eplet Eşleşmesi

Öz

Böbrek nakli, son dönem böbrek yetmezliğinin tek küratif tedavisidir. Böbrek naklinde immünolojik uyumluluk, böbrek alıcısı ile donör arasındaki insan lökosit antijenine (HLA) uyumuna bağlıdır. HLA uyumsuzluğunun artması, de novo donöre özgü HLA antikorlarının (dnDSA) oluşmasına neden olabilir. Bu antikorlar, böbrek dokusuna karşı immünolojik reaksiyonları baş-latarak organ reddine (rejeksiyon ve greft kaybı) yol açabilir. Genel olarak, alıcı ve donör arasındaki HLA doku uyumsuzluğunun azalmasıyla nakil sonrası böbrek dokularına karşı oluşabilecek rejeksiyon riski azalırken, uyumsuzluğun artmasıyla rejeksiyon riski artabilir. HLA epitopları, 25 amino asitten oluşan, antijen sunan hücreler ile T hücre reseptörlerinin bağlanmasını sağlayan özelleşmiş yapılardır. Bu bağlanma noktaları fonksiyonel epitop veya eplet olarak tanımlanır ve 2-5 amino asit uzunluğunda olabilir. Bu bağlanma noktaları bilgisayar algoritmaları tarafından tahmin edilebilir. Bu algoritmalar sayesinde, alıcı ve donör arasındaki HLA uyumlu-luğu daha hassas bir şekilde değerlendirilebilir. Eplet uyumsuzlukları, gelecekte organ nakli açısından kritik bir biyobelirteç olabilir. Böbrek nakli alıcı ve donör arasındaki eplet uyumsuzluğunun tespiti, uyumsuz epletlerin risk değerlendirmesi ve buna göre planlanmış immünolojik klinik süreçler nakil sonrası böbrek greft sağkalımını uzatabilir. Greft sağkalımının uzaması, böbrek naklinde klinik sonuçların iyileştirilmesi, alıcının yaşam kalitesinin artırılması ve sağlık sisteminde maliyetlerin azaltılmasına katkıda bulunabilir. Bu derlemede, eplet eşleştirmenin geleneksel HLA antijen eşleşmesine kıyasla avantajları, immünolojik uyumluluğun artırılmasındaki rolü ve klinik değerlendirilmesi ele alınmaktadır.

Anahtar Kelimeler

• Böbrek transplantasyonu
• HLA uyumu
• HLA epitopları,
• Eplet eşleşmesi
• Donöre özgü antikorlar

An Alternative Approach to Traditional HLA Incompatibility in Kidney Transplantation: HLA Eplet Matching

Öz

Kidney transplantation is the only curative treatment for end-stage renal disease. Immunological compatibility in kidney transplantation depends on the compatibility of the human leukocyte antigen (HLA) between the kidney recipient and the donor. Increased HLA incompatibility can result in the formation of de novo donor-specific HLA antibodies (dnDSA). These antibodies can initiate immunological reactions against kidney tissue, leading to organ rejection (rejection and graft loss). In general, the risk of rejection against kidney tissues after transplantation decreases with the decrease in HLA tissue incompatibility between the recipient and the donor, while the risk of rejection may increase with the increase in incompatibility. HLA epitopes are specific portions of HLA molecules, consisting of 25 amino acids, to which antibodies and T cell receptors bind. These binding points are defined as functional epitopes or eplets and can be 2-5 amino acids long. These attachment points can be predicted by computer algorithms. Thanks to these algorithms, the HLA compatibility between the recipient and the donor can be assessed more precisely. Eplet incompatibilities may be a critical biomarker for organ transplantation in the future. Detection of eplet incompatibility between kidney transplant recipient and donor, together with risk assessment of incompatible eplets and immunological clinical processes may prolong kidney graft survival after transplantation. Prolonging graft survival can contribute to improving clinical outcomes in kidney transplantation, improving the recipient's quality of life, and reducing costs in the healthcare system. In this review, the advantages of eplet matching compared to traditional HLA antigen matching, its role in increasing immunological compatibility, and its clinical evaluation are discussed.

Anahtar Kelimeler

• Kidney transplantation
• HLA compatibility
• HLA epitopes
• Eplet matching
• Donor-specific antibodies

Kaynakça

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