Böbrek Nakli Adaylarında Panel-reaktif Antikor Pozitifliği ile Trombosit İndeksleri Arasındaki İlişki

Öz

Panel reaktif antikor (PRA), transplantasyon öncesi immünolojik duyarlanmanın yerleşik bir göstergesidir. Bununla birlikte, PRA pozitifliği ile rutin olarak ölçülen trombosit indeksleri arasındaki ilişki henüz net değildir. Bu retrospektif gözlemsel çalışmada, erişkin böbrek nakli adaylarında PRA pozitifliği ile trombosit sayısı ve trombosit indeksleri arasındaki ilişkinin araştırılması amaçlandı. Toplam 450 böbrek nakli adayı tarandı. Aktif enfeksiyonu bulunanlar, trombosit indekslerini etkileyebilecek ilaç kullananlar ve eş zamanlı PRA ve tam kan sayımı ölçümleri bulunmayan hastalar dışlandıktan sonra 208 hasta çalışmaya dâhil edildi. Tüm katılımcıların demografik, laboratuvar ve immünolojik verileri kaydedildi. Hastaların 58’i (%27,9) PRA pozitif (PRA >%10), 150’si (%72,1) ise PRA negatif (PRA ≤%10) olarak sınıflandırıldı. Çalışmaya katılan hastaların 114’ü (%54,8) kadın, 94’ü (%45,2) erkekti. PRA negatif hastalarla karşılaştırıldığında, PRA pozitif hastalarda kadın oranı daha yüksek (%77,6 ve %46,0; p < 0,001), medyan diyaliz süresi daha uzun (51,5 [28,5–85,0] ve 26,0 [2,75–50,25] ay; p < 0,001) ve medyan trombosit dağılım genişliği (PDW) daha yüksekti (16,45 [16,07–16,90] ve 16,20 [15,80–16,60] fL; p = 0,006). Buna karşılık, trombosit sayısı, ortalama trombosit hacmi ve plateletcrit değerleri gruplar arasında benzerdi. Çok değişkenli analizde kadın cinsiyet, daha uzun diyaliz süresi, periton diyalizi ve daha yüksek PDW değerleri PRA pozitifliği ile bağımsız olarak ilişkiliydi. Bununla birlikte, PRA pozitif ve PRA negatif gruplar arasındaki mutlak PDW farkı küçüktü (sırasıyla 16,45 ve 16,20 fL). Böbrek nakli adaylarında daha yüksek PDW değerleri PRA pozitifliği ile ilişkili bulundu. Bununla birlikte, gruplar arasındaki farkın küçük olması ve çalışmanın gözlemsel tasarımı, PDW’nin klinik yararlılığına ilişkin kesin bir sonuca varılmasına olanak vermemektedir. Bu ilişkinin doğrulanması için ileriye dönük çalışmalara ihtiyaç vardır.

Anahtar Kelimeler

• böbrek nakli
• insan lökosit antijeni
• panel reaktif antikor
• trombosit
• trombosit dağılım genişliği

Association Between Panel-reactive Antibody Positivity and Platelet Indices in Kidney Transplant Candidates

Öz

Panel-reactive antibody (PRA) is an established marker of pre-transplant immunological sensitization; however, the relationship between PRA positivity and routinely measured platelet indices remains unclear. The present retrospective observational study investigated the association between PRA positivity and platelet count, as well as indices, in adult kidney transplant candidates. Following the screening of 450 candidates, 208 were deemed eligible after excluding patients with active infection, those using medications affecting platelet indices, or those for whom simultaneous PRA and complete blood count measurements were unavailable. The demographic, laboratory, and immunological data of all participants were recorded. Of these, 58 (27.9%) were classified as PRA-positive (PRA >10%) and 150 (72.1%) as PRA-negative (PRA ≤10%). The cohort comprised 114 women (54.8%) and 94 men (45.2%). Compared with PRA-negative patients, PRA-positive patients had a higher proportion of women (77.6% vs. 46.0%; p < 0.001), longer median dialysis duration (51.5 [28.5–85.0] vs. 26.0 [2.75–50.25] months; p < 0.001), and higher median platelet distribution width (PDW; 16.45 [16.07–16.90] vs. 16.20 [15.80–16.60] fL; p = 0.006). However, platelet count, mean platelet volume, and plateletcrit were comparable. In multivariable analysis, female sex, longer dialysis duration, peritoneal dialysis, and higher PDW values were independently associated with PRA positivity, although the absolute difference between the PRA-positive and PRA-negative groups was small (16.45 vs. 16.20 fL). Higher PDW was associated with PRA positivity in kidney transplant candidates; however, the small between-group difference and the observational design preclude conclusions regarding its clinical utility. Further prospective studies are required to confirm this association.

Anahtar Kelimeler

• kidney transplantation
• human leukocyte antigen
• panel-reactive antibody
• platelet distribution width
• platelet

Kaynakça

1. 1. Wolfe RA, Ashby VB, Milford EL, Ojo AO, Ettenger RE, Agodoa LY, et al. Comparison of mortality in all patients on dialysis, patients on dialysis awaiting transplantation, and recipients of a first cadaveric transplant. N Engl J Med 1999;341:1725-1730. doi:10.1056/NEJM199912023412303.
2. 2. Clayton PA, McDonald SP, Russ GR, Chadban SJ. Long-term outcomes after acute rejection in kidney transplant recipients: an ANZDATA analysis. J Am Soc Nephrol 2019;30:1697-1707. doi:10.1681/ASN.2018111101.
3. 3. Vella J, Brennan DC, Legendre C, Lam AQ. Transplantation immunobiology. In: Connor RF, editor. UpToDate [Internet]. Waltham (MA): Wolters Kluwer; 2026 [cited 2026 Jul 16]. Available from: https://www.uptodate.com/contents/ transplantation-immunobiology
4. 4. Altindal M, Guldan M, Ozbek L, Abdel-Rahman SM, Unlu S, Murt A, et al. Desensitization in HLA incompatible kidney transplant recipients: current strategies and emerging perspectives. Clin Kidney 2025;18:sfaf219. doi:10.1093/ckj/sfaf219.
5. 5. Jordan SC, Pescovitz MD. Presensitization: the problem and its management. Clin J Am Soc Nephrol 2006;1:421-432. doi:10.2215/CJN.01651105.
6. 6. Jackson KR, Segev DL. Rethinking incompatibility in kidney transplantation. Am J Transplant 2022;22:1031-1036. doi:10.1111/ajt.16826.
7. 7. Mamode N, Bestard O, Claas F, Furian L, Griffin S, Legendre C, et al. European guideline for the management of kidney transplant patients with HLA antibodies: by the European Society for Organ Transplantation Working Group. Transpl Int 2022;35:10511. doi:10.3389/ti.2022.10511.
8. 8. Ali RA, Wuescher LM, Worth RG. Platelets: essential components of the immune system. Curr Trends Immunol 2015;16:65-78. PMID: 27818580. PMCID: PMC5096834.

9. 9. Verschoor A, Neuenhahn M, Navarini AA, Graef P, Plaumann A, Seidlmeier A, et al. A platelet-mediated system for shuttling blood-borne bacteria to CD8α+ dendritic cells depends on glycoprotein GPIb and complement C3. Nat Immunol 2011;12:1194-1201. doi:10.1038/ni.2140.
10. 10. Chapman LM , Aggrey AA, Field DJ, Srivastava K, Ture S, Yui K, et al. Platelets present antigen in the context of MHC class I. J Immunol 2012;189:916-923. doi:10.4049/jimmunol.1200580.
11. 11. Boshkov LK, Kelton JG, Halloran PF. HLA-DR expression by platelets in acute idiopathic thrombocytopenic purpura. Br J Haematol 1992;81:552-557. doi:10.1111/j.1365-2141.1992.tb02991.x.
12. 12. Semple JW, Milev Y, Cosgrave D, Mody M, Hornstein A, Blanchette V, et al. Differences in serum cytokine levels in acute and chronic autoimmune thrombocytopenic purpura: relationship to platelet phenotype and antiplatelet T-cell reactivity. Blood 1996;87:4245-4254. PMID: 8639783.
13. 13. Elton CM, Smethurst PA, Eggleton P, Farndale RW. Physical and functional interaction between cell-surface calreticulin and the collagen receptors integrin α2β1 and glycoprotein VI in human platelets. Thromb Haemost 2002;88:648-654. PMID: 12362238.
14. 14. Gerdes N, Zhu L, Ersoy M, Hermansson A, Hjemdahl P, Hu H, et al. Platelets regulate CD4+ T-cell differentiation via chemokines in humans. Thromb Haemost 2011;106:353-362. doi:10.1160/TH11-01-0020.
15. 15. Morrell CN, Aggrey AA, Chapman LM, Modjeski KL. Emerging roles for platelets as immune and inflammatory cells. Blood 2014;123:2759-2767. doi:10.1182/blood-2013-11-462432.
16. 16. Buoro S, Seghezzi M, Manenti B, Pacioni A, Carobene A, Ceriotti F, et al. Biological variation of platelet parameters determined by the Sysmex XN hematology analyzer. Clin Chim Acta 2017;470:125-132. doi:10.1016/j.cca.2017.05.004.
17. 17. Ding Q, Wang F, Guo X, Liang M. The relationship between mean platelet volume and metabolic syndrome in patients with type 2 diabetes mellitus. Medicine 2021;100:e25303. doi:10.1097/MD.0000000000025303.
18. 18. Korniluk A, Koper-Lenkiewicz OM, Kaminska J, Kemona H, Dymicka-Piekarska V. Mean platelet volume (MPV): new perspectives for an old marker in the course and prognosis of inflammatory conditions. Mediators Inflamm 2019;2019:9213074. doi:10.1155/2019/9213074.
19. 19. Chaudhary PK, Kim Sa, Kim So. An insight into recent advances on platelet function in health and disease. Int J Mol Sci 2022;23:6022-6061. doi:10.3390/ijms23116022.
20. 20. Bilen Y, Cankaya E, Keles M, Gulcan E, Uyanık A, Turkeli M, et al. Does decreased mean platelet volume predict inflammation in chronic renal failure, dialysis, and transplanted patients? Ren Fail 2014;36:69-72. doi:10.3109/0886022X.2013.832310.
21. 21. Lokesh S, Green SR, Mathew TK, Hemachandar R, Kumar A, Tiwari SR, et al. A comparative study of platelet parameters in end stage kidney disease patients undergoing hemodialysis and healthy individuals. Int J Adv Med 2016;3:559-563. doi:10.18203/2349-3933.ijam20162022.
22. 22. Scherlinger M, Guillotin V, Truchetet ME, Contin-Bordes C, Sisirak V, Duffau P, et al. Systemic lupus erythematosus and systemic sclerosis: All roads lead to platelets. Autoimmun Rev 2018;17:625-635. doi:10.1016/j.autrev.2018.01.012.
23. 23. Karacaglar E, Bal U, Ciftci O, Turgay O, Yilmaz M, Sade E, et al. Predictive value of hematologic parameters for detecting asymptomatic graft rejection after heart transplant: preliminary results. Exp Clin Transplant 2015;13:146-148. doi:10.6002/ect.tdtd2015.P78.
24. 24. Sever MŞ. Anti-HLA antikorlar, sensitizasyon ve lenfosit cross-match testi. In: Böbrek transplantasyonu: temel bilgiler ve uygulama rehberi. 1st ed. İstanbul: Nobel Tıp Kitabevleri; 2019:175-184.
25. 25. Vagdatli E, Gounari E, Lazaridou E, Katsibourlia E, Tsikopoulou F, Labrianou I. Platelet distribution width: a simple, practical and specific marker of activation of coagulation. Hippokratia 2010;14:28-32. PMID: 20411056. PMCID: PMC2843567.
26. 26. Izzi B, Gialluisi A, Gianfagna F, Orlandi S, De Curtis A, Magnacca S, et al. Platelet distribution width is associated with p-selectin dependent platelet function: results from the moli-family cohort study. Cells 2021;10:2737. doi:10.3390/cells10102737.
27. 27. Morrell CN, Sun H, Swaim AM, Baldwin WM. Platelets an inflammatory force in transplantation. Am J Transplant 2007;7:2447-2454. doi:10.1111/j.1600-6143.2007.01958.x.
28. 28. Yan C, Wu H, Fang X, He J, Zhu F. Platelet, a key regulator of innate and adaptive immunity. Front Med (Lausanne) 2023; 10:1074878. doi:10.3389/fmed.2023.1074878.
29. 29. Scherlinger M, Richez C, Tsokos GC, Boilard E, Blanco P. The role of platelets in immune-mediated inflammatory diseases. Nat Rev Immunol 2023;23:495-510. doi:10.1038/s41577-023-00834-4.
30. 30. Bhaskaran MC, Heidt S, Muthukumar T. Principles of virtual crossmatch testing for kidney transplantation. Kidney Int Rep 2022;7:1179-1188. doi:10.1016/j.ekir.2022.03.006.
31. 31. Klein SL, Flanagan KL. Sex differences in immune responses. Nat Rev Immunol 2016;16:626-638. doi:10.1038/nri.2016.90.
32. 32. Klein SL, Marriott I, Fish EN. Sex-based differences in immune function. Trans R Soc Trop Med Hyg 2015;109:9-15. doi:10.1093/trstmh/tru167.
33. 33. Malho A, Malheiro J, Fonseca I, Martins LS, Pedroso S, Almeida M, et al. Advantages of kidney transplant precocity in graft long-term survival. Transplant Proc 2012;44:2344-2347. doi:10.1016/j.transproceed.2012.07.030.
34. 34. Chadban SJ, Ahn C, Axelrod DA, Foster BJ, Kasiske BL, Kher V, et al. KDIGO clinical practice guideline on the evaluation and management of candidates for kidney transplantation. Transplantation 2020;104:S11-S103. doi:10.1097/TP.0000000000003136.
35. 35. Willicombe M, Roberts DJ. Transfusion-induced HLA sensitization in wait-list patients and kidney transplant recipients. Kidney Int 2024;106:795-805. doi:10.1016/j.kint.2024.07.030.