Dergiler / Akdeniz Tıp Dergisi / 2026 / Cilt: 12 Sayı: 1

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

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

Ümit Aslanhan(SAĞLIK BİLİMLERİ ÜNİVERSİTESİ, HAMİDİYE SAĞLIK BİLİMLERİ ENSTİTÜSÜ, İMMÜNOLOJİ (DR))0000-0003-3126-8694
Gülbu Işıtmangil(SAĞLIK BİLİMLERİ ÜNİVERSİTESİ, HAMİDİYE SAĞLIK BİLİMLERİ ENSTİTÜSÜ, TIBBİ MİKROBİYOLOJİ (DR))0000-0003-4243-8003
Sevgi Kalkanlı Taş(SAĞLIK BİLİMLERİ ÜNİVERSİTESİ, HAMİDİYE SAĞLIK BİLİMLERİ ENSTİTÜSÜ, İMMÜNOLOJİ (DR))0000-0001-5288-6040
Sayfa
—
Yayın Tarihi
2026-03-25
🏛️Bu makalenin bibliyografik verileri ve tam metin bağlantısı DergiPark üzerinden sağlanmıştır.
DergiPark Kaydı ↗
✨

Yapay Zeka Hızlı Bakış & Çıkarımlar

AI Insight
⚡ TL;DR(1 Cümlede Hızlı Çıkarım)

Bu derlemede, eplet eşleştirmenin geleneksel HLA antijen eşleşmesine kıyasla avantajları, immünolojik uyumluluğun artırılmasındaki rolü ve klinik değerlendirilmesi ele alınmaktadır.

📌 3 Maddede Bu Makale

🎯
Amaç & Hipotez:Böbrek nakli, son dönem böbrek yetmezliğinin tek küratif tedavisidir.
📊
Temel Bulgular & Veri:HLA epitopları, 25 amino asitten oluşan, antijen sunan hücreler ile T hücre reseptörlerinin bağlanmasını sağlayan özelleşmiş yapılardır.
💡
Sonuç & Katkı:Bu derlemede, eplet eşleştirmenin geleneksel HLA antijen eşleşmesine kıyasla avantajları, immünolojik uyumluluğun artırılmasındaki rolü ve klinik değerlendirilmesi ele alınmaktadır.
🔬Tür:Literatür & Derleme Çalışması
📍Kapsam:Genişletilmiş Akademik Örneklem
⚙️Değişkenler:Böbrek transplantasyonu · HLA uyumu · HLA epitopları

Özet

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.

Abstract

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.

🔖

Bu Makaleye Atıf Yap

Aslanhan, Ü., Işıtmangil, G., Taş, S. K. (2026). Böbrek Naklinde Geleneksel HLA Uyumsuzluğuna Alternatif Bir Yaklaşım: HLA Eplet Eşleşmesi. Akdeniz Tıp Dergisi, Cilt: 12 Sayı: 1. https://doi.org/10.53394/akd.1622769

📄 Tam Metin PDF Okuyucu

📄

PDF görüntüleyici hazırlanıyor...

Kaynakça (47)

  1. Opelz G, Döhler B. Effect of hu-man leukocyte antigen compatibi-lity on kidney graft survival: Comparative analysis of two de-cades. Transplantation. 2007;84(2):137–43.
  2. Tait BD, Süsal C, Gebel HM, Nickerson PW, Zachary AA, Claas FHJ, Reed EF, Bray RA, Campbell P, Chapman JR, Coates PT, Colvin RB, Cozzi E, Doxia-dis IIN, Fuggle S V., Gill J, Glotz D, Lachmann N, Mohanakumar T, Suciu-Foca N, Sumitran-Holgersson S, Tanabe K, Taylor CJ, Tyan DB, Webster A, Zeevi A, Opelz G. Consensus guideli-nes on the testing and clinical ma-nagement issues associated with HLA and Non-HLA antibodies in transplantation. Transplantation. 2013;95(1):19–47.
  3. Duquesnoy RJ, Takemoto S, De Lange P, Doxiadis IIN, Schreuder GMT, Persijn GG, Claas FHJ. HLAMatchmaker: A molecularly based algorithm for histocompati-bility determination. III. Effect of matching at the HLA-A,B amino acid triplet level on kidney transp-lant survival. Transplantation. 2003;75(6):884–9.
  4. Tambur AR, Claas FHJ. HLA epitopes as viewed by antibodies: What Is it all about? American Jo-urnal of Transplantation. 2015;15(5):1148–54.
  5. Wiebe C, Nickerson P. Strategic Use of Epitope Matching to Imp-rove Outcomes. Transplantation. 2016;100(10):2048–52.
  6. Doxiadis I, Loeffler-Wirth H, Lachmann N, Lehmann C. A Short History of B-Cell HLA Epi-topes. Transfus Med Hemother. 2024;51(3):152–7.
  7. Lim WH, Chadban SJ, Clayton P, Budgeon CA, Murray K, Camp-bell SB, Cohney S, Russ GR, Mcdonald SP. Human leukocyte antigen mismatches associated with increased risk of rejection, graft failure, and death indepen-dent of initial immunosuppression in renal transplant recipients. Clin Transplant. 2012;26(4).
  8. Süsal C, Opelz G. Current role of human leukocyte antigen matc-hing in kidney transplantation. Curr Opin Organ Transplant. 2013;18(4):438–44.
  9. Williams RC, Opelz G, McGar-vey CJ, Weil EJ, Chakkera HA. The Risk of Transplant Failure With HLA Mismatch in First Adult Kidney Allografts From Deceased Donors. Transplanta-tion. 2016;100(5):1094–102.
  10. Opelz G, Döhler B. Impact of HLA mismatching on incidence of posttransplant non-hodgkin lymphoma after kidney transplan-tation. Transplantation. 2010;89(5):567–72.
  11. Opelz G, Döhler B. Association of HLA mismatch with death with a functioning graft after kidney transplantation: a collaborative transplant study report. Am J Transplant. 2012;12(11):3031–8.
  12. Meier-Kriesche HU, Scornik JC, Susskind B, Rehman S, Schold JD. A lifetime versus a graft life approach redefines the importance of HLA matching in kidney transplant patients. Transplanta-tion. 2009;88(1):23–9.
  13. Fuggle S V., Martin S. Tools for human leukocyte antigen antibody detection and their application to transplanting sensitized patients. Transplantation. 2008;86(3):384–90.
  14. Süsal C, Fichtner A, Tönshoff B, Mehrabi A, Zeier M, Morath C. Clinical Relevance of HLA Anti-bodies in Kidney Transplantation: Recent Data from the Heidelberg Transplant Center and the Colla-borative Transplant Study. J Im-munol Res. 2017;2017.
  15. Mattoo A, Jaffe IS, Keating B, Montgomery RA, Mangiola M. Improving long-term kidney al-lograft survival by rethinking HLA compatibility: from molecu-lar matching to non-HLA genes. Front Genet. 2024;15:1442018.
  16. Mangiola M, Ellison MA, Marrari M, Bentlejewski C, Sadowski J, Zern D, Niemann M, Feingold B, Webber SA, Zeevi A. Immunolo-gic risk stratification of pediatric heart transplant patients by com-bining HLAMatchmaker and PIRCHE-II. J Heart Lung Transp-lant. 2022;41(7):952–60.
  17. Duquesnoy RJ. HLAM-MATCHMAKER: a molecularly based donor selection algorithm for highly alloimmunized patients. Transplant Proc. 2001;33(1–2):493–7.
  18. Duquesnoy RJ, Witvliet M, Doxi-adis IIN, De Fijter H, Claas FHJ. HLAMatchmaker-based strategy to identify acceptable HLA class I mismatches for highly sensitized kidney transplant candidates. Transpl Int. 2004;17(1):22–30.
  19. Oguz FS, Oguz SR, Ogret Y, Ka-radeniz TS, Ciftci HS, Karatas S, Kivanc D, Aydin F. Distribution of HLA epitope frequencies in Turkish population. Turkish Jour-nal of Biochemistry. 2022;47(3):289–95.
  20. Kumru Sahin G, Unterrainer C, Süsal C. Critical evaluation of a possible role of HLA epitope matching in kidney transplanta-tion. Transplant Rev (Orlando). 2020;34(2).
  21. Silva E, Alba A, Castro A, Car-rascal M, Buckel E, Aguiló J, Herzog C, Calabrán L, Morales J, Fierro JA. Evaluation of HLA Matchmaker compatibility as pre-dictor of graft survival and pre-sence of Anti-HLA antibodies. Transplant Proc. 2010;42(1):266–9.
  22. Ladowski JM, Mullins H, Romine M, Kloda D, Young C, Hauptfeld-Dolejsek V, Houp J, Locke J. Ep-let mismatch scores and de novo donor-specific antibody develop-ment in simultaneous pancreas-kidney transplantation. Hum Im-munol. 2021;82(3):139–46.
  23. Do Nguyen HT, Wong G, Chap-man JR, McDonald SP, Coates PT, Watson N, Russ GR, D’Orsogna L, Lim WH. The As-sociation Between Broad Antigen HLA Mismatches, Eplet HLA Mismatches and Acute Rejection After Kidney Transplantation. Transplant Direct. 2016;2(12):E120.
  24. Sapir-Pichhadze R, Tinckam K, Quach K, Logan AG, Laupacis A, John R, Beyene J, Kim SJ. HLA-DR and -DQ eplet mis-matches and transplant glomeru-lopathy: a nested case-control study. Am J Transplant. 2015;15(1):137–48.
  25. Wiebe C, Kosmoliaptsis V, Poc-hinco D, Gibson IW, Ho J, Birk PE, Goldberg A, Karpinski M, Shaw J, Rush DN, Nickerson PW. HLA-DR/DQ molecular mismatch: A prognostic biomarker for primary alloimmunity. Am J Transplant. 2019;19(6):1708–19.
  26. Wiebe C, Pochinco D, Blydt-Hansen TD, Ho J, Birk PE, Kar-pinski M, Goldberg A, Storsley LJ, Gibson IW, Rush DN, Nic-kerson PW. Class II HLA epitope matching-A strategy to minimize de novo donor-specific antibody development and improve outco-mes. Am J Transplant. 2013;13(12):3114–22.
  27. Wiebe C, Nevins TE, Robiner WN, Thomas W, Matas AJ, Nic-kerson PW. The Synergistic Ef-fect of Class II HLA Epitope-Mismatch and Nonadherence on Acute Rejection and Graft Survi-val. Am J Transplant. 2015;15(8):2197–202.
  28. Wiebe C, Rush DN, Nevins TE, Birk PE, Blydt-Hansen T, Gibson IW, Goldberg A, Ho J, Karpinski M, Pochinco D, Sharma A, Stors-ley L, Matas AJ, Nickerson PW. Class II Eplet Mismatch Modula-tes Tacrolimus Trough Levels Required to Prevent Donor-Specific Antibody Development. J Am Soc Nephrol. 2017;28(11):3353–62.
  29. Kosmoliaptsis V, Sharples LD, Chaudhry AN, Halsall DJ, Brad-ley JA, Taylor CJ. Predicting HLA class II alloantigen immu-nogenicity from the number and physiochemical properties of ami-no acid polymorphisms. Transp-lantation. 2011;91(2):183–90.
  30. Kosmoliaptsis V, Mallon DH, Chen Y, Bolton EM, Bradley JA, Taylor CJ. Alloantibody Respon-ses After Renal Transplant Failure Can Be Better Predicted by Do-nor-Recipient HLA Amino Acid Sequence and Physicochemical Disparities Than Conventional HLA Matching. Am J Transplant. 2016;16(7):2139–47.
  31. Duquesnoy RJ. Are We Ready for Epitope-Based HLA Matching in Clinical Organ Transplantation? Transplantation. 2017;101(8):1755–65.
  32. Mallon DH, Kling C, Robb M, Ellinghaus E, Bradley JA, Taylor CJ, Kabelitz D, Kosmoliaptsis V. Predicting Humoral Alloimmunity from Differences in Donor and Recipient HLA Surface Electros-tatic Potential. The Journal of Immunology. 2018;201(12):3780–92.
  33. Wiebe C, Kosmoliaptsis V, Poc-hinco D, Taylor CJ, Nickerson P. A Comparison of HLA Molecular Mismatch Methods to Determine HLA Immunogenicity. Transplan-tation. 2018;102(8):1338–43.
  34. El-Awar N, Lee JH, Tarsitani C, Terasaki PI. HLA class I epitopes: recognition of binding sites by mAbs or eluted alloantibody con-firmed with single recombinant antigens. Hum Immunol. 2007;68(3):170–80.
  35. Duquesnoy RJ, Marrari M. Corre-lations between Terasaki’s HLA class I epitopes and HLAMatch-maker-defined eplets on HLA-A, -B and -C antigens. Tissue Anti-gens. 2009;74(2):117–33.
  36. Marrari M, Duquesnoy RJ. Corre-lations between Terasaki’s HLA class II epitopes and HLAMatch-maker-defined eplets on HLA-DR and -DQ antigens. Tissue Anti-gens. 2009;74(2):134–46.
  37. Geneugelijk K, Thus KA, Spi-erings E. Predicting alloreactivity in transplantation. J Immunol Res. 2014;2014.
  38. Otten HG, Calis JJA, Keşmir C, van Zuilen AD, Spierings E. Pre-dicted indirectly recognizable HLA epitopes presented by HLA-DR correlate with the de novo development of donor-specific HLA IgG antibodies after kidney transplantation. Hum Immunol. 2013;74(3):290–6.
  39. Geneugelijk K, Hönger G, Van Deutekom HWM, Thus KA, Keşmir C, Hösli I, Schaub S, Spi-erings E. Predicted Indirectly Re-cognizable HLA Epitopes Presen-ted by HLA-DRB1 Are Related to HLA Antibody Formation Du-ring Pregnancy. Am J Transplant. 2015;15(12):3112–22.
  40. Lachmann N, Niemann M, Rein-ke P, Budde K, Schmidt D, Hal-leck F, Pruß A, Schönemann C, Spierings E, Staeck O. Donor-Recipient Matching Based on Predicted Indirectly Recognizable HLA Epitopes Independently Predicts the Incidence of De No-vo Donor-Specific HLA Antibo-dies Following Renal Transplanta-tion. Am J Transplant. 2017;17(12):3076–86.
  41. Geneugelijk K, Niemann M, Dry-lewicz J, van Zuilen AD, Joosten I, Allebes WA, van der Meer A, Hilbrands LB, Baas MC, Erik Hack C, van Reekum FE, Verhaar MC, Kamburova EG, Bots ML, Seelen MAJ, Sanders JS, Hepke-ma BG, Lambeck AJ, Bungener LB, Roozendaal C, Tilanus MGJ, Vanderlocht J, Voorter CE, Wie-ten L, van Duijnhoven EM, Ge-lens M, Christiaans MHL, van It-tersum FJ, Nurmohamed A, Lardy JNM, Swelsen W, van der Pant KA, van der Weerd NC, ten Ber-ge IJM, Bemelman FJ, Hoitsma A, van der Boog PJM, de Fijter JW, Betjes MGH, Heidt S, Roe-len DL, Claas FH, Otten HG, Spierings E. PIRCHE-II Is Rela-ted to Graft Failure after Kidney Transplantation. Front Immunol. 2018;9(MAR).
  42. Daniëls L, Naesens M, Bosmans JL, Abramowicz D, Nagler E, Van Laecke S, Peeters P, Kuypers D, Emonds MP. The clinical sig-nificance of epitope mismatch load in kidney transplantation: A multicentre study. Transpl Immu-nol. 2018;50:55–9.
  43. Kramer CSM, Koster J, Haasnoot GW, Roelen DL, Claas FHJ, He-idt S. HLA-EMMA: A user-friendly tool to analyse HLA class I and class II compatibility on the amino acid level. HLA. 2020;96(1):43–51.
  44. Santos E, Spensley K, Gunby N, Worthington J, Roufosse C, Anand A, Willicombe M. Appli-cation of HLA molecular level mismatching in ethnically diverse kidney transplant recipients recei-ving a steroid-sparing immuno-suppression protocol. American Journal of Transplantation. 2024;24(7):1218–32.
  45. Ellison M, Mangiola M, Marrari M, Bentlejewski C, Sadowski J, Zern D, Kramer CSM, Heidt S, Niemann M, Xu Q, Dipchand AI, Mahle WT, Rossano JW, Canter CE, Singh TP, Zuckerman WA, Hsu DT, Feingold B, Webber SA, Zeevi A. Immunologic risk strati-fication of pediatric heart transp-lant patients by combining HLA-EMMA and PIRCHE-II. Front Immunol. 2023;14.
  46. Crowe DO. The effect of cross-reactive epitope group matching on allocation and sensitization. Clin Transplant. 2003;17 Suppl 9(SUPPL. 9):13–6.
  47. Duquesnoy RJ. Reflections on HLA Epitope-Based Matching for Transplantation. Front Immunol. 2016;7(NOV).