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Long-Term Effects of Antibodies Against Human Leukocyte Antigens Detected by Flow Cytometry in the First Year After Renal Transplantation

Yıl 2013, Cilt: 2013 Sayı: 1, 37 - 45, 01.01.2013
https://doi.org/10.5152/balkanmedj.2012.071

Öz

Objective: In this study, we aimed to investigate the incidence, dynamics and profiles of human leukocyte antigen (HLA)-directed antibodies developed after transplantation and their impact on graft rejection and outcome in kidney recipients. Study Design: Prospective follow-up study. Material and Methods: A total of 56 kidney recipients were monitored at 1st, 6th and 12th months for the development of anti-HLA antibodies using bead based flow-cytometry assays (Flow PRA tests). Results: In 21 (37.5%) patients, panel reactive antibodies (PRA) was positive after transplantation, however, in 35 (62.5%) patients PRA was found negative. Twelve (57.1%) patients with post-transplantation HLA-reactive antibodies [PRA (+)] and 8 (22.9%) patients with no detectable alloantibodies [PRA (-)] were developed allograft rejection (p=0.010). In the PRA positive patient group the rates of early period infection and delayed graft function (DGF) were higher than the PRA negative patient group. Serum creatinine levels of PRA positive group at 6. and 12. months after transplantation were significantly higher than the PRA negative group (p=0.015 and p=0.048, respectively). The rejection rates of patients who had class I and II HLA antibodies were significantly higher than the patients who had either class I or II HLA antibodies (p=0.011). Acute rejection rates were significantly higher in patients who had class I and II HLA antibodies at the first month (p=0.007). Conclusion: Higher occurrence of rejection episodes in PRA positive group may show the importance of anti-HLA antibody monitoring using Flow-PRA after renal transplantation as a prognostic marker in terms of graft survival. Turkish Başlık: Böbrek Nakli Sonrası Birinci Yılda Akım Sitometri ile Saptanan İnsan Lökosit Antijenlerine Özgü Antikorların Uzun Dönem Etkileri Anahtar Kelimeler: Anti-HLA antikorları, akım sitometri, böbrek nakli Amaç: Bu çalışmada transplantasyon sonrası gelişen İnsan Lökosit Antijenlerine Özgü Antikorların (anti- Human Leukocytes Antigen-(HLA) antibody) etkilerini, dinamik ve profillerini araştırmayı amaçladık. Gereç ve Yöntemler: Toplam 56 böbrek alıcısı akım sitometri temelli boncuk testleri ile 1., 6. ve 12. aylarda anti-HLA antikorları izlendi. Bulgular: Nakil sonrası hastaların 21'inde (% 37,5), panel reaktif antikorlar (PRA)pozitif iken, 35'inde (% 62,5) negatif olduğu bulundu. Nakil sonrası Panel reaktif antikora sahip [PRA(+)] hastaların 12'sinde (%57,1) ve panel reaktif antikor saptanmayan hastaların 8'inde (% 22,9) allograft rejeksiyonu gelişti (p=0.010). PRA pozitif hasta grubunda erken dönem infeksiyon oranı ve gecikmiş graft fonksiyonu (delayed graft function-DGF) oranı, PRA negatif hasta grubundan daha yüksekti. PRA pozitif grupta nakil sonrası 6. ve 12. aylardaki serum kreatinin düzeyleri, PRA negatif gruptan anlamlı derecede yüksekti (p= 0,015, ve p0 0.048 sırasıyla). Sınıf I ve sınıf II HLA antikorları olan hastaların rejeksiyon oranı, ya sınıf I yada sınıf II HLA antikorları olan hastalardan önemli derecede yüksekti (p= 0.011). Akut rejeksiyon oranları birinci ayda sınıf I ve sınıf II HLA antikorları olan hastalarda anlamlı derecede yüksekti ( p=0.007) Sonuç: Böbrek transplantasyonu sonrasında PRA pozitif grupta rejeksiyon ataklarının daha yüksek olması, graft sağkalımında prognostik belirteç olarak Flow-PRA ile anti-HLA antikorlarının takip edilmesinin önemini gösterebilir.

Kaynakça

  • Mihaylova A, Baltadjieva D, Boneva P, Ivanova M, Penkova K, Marinova D, et al. Clinical relevance of anti-HLA antibodies detected by flow-cytometry bead-based assays--single-center experience. Hum Immunol 2006;67:787-94. [CrossRef]
  • Panigrahi A, Gupta N, Siddiqui JA, Margoob A, Bhowmik D, Guleria S, et al. Post- transplant development of MICA and antiHLA antibodies is associated with acute rejection episodes and renal allograft loss. Hum Immunol 2007;68:362-7. [CrossRef]
  • Van der Mast BJ, van Besouw NM, Witvliet MD, de Kuiper P, Smak Gregoor P, van Gelder T, et al. Formation of donorspecific human leukocyte antigen antibodies after kidney transplantation:correlation with acute rejection and tapering of immunosuppression. Transplantation 2003;75:871-7. [CrossRef]
  • Lee PC, Zhu L, Terasaki PI, Everly MJ. HLA-specific antibodies developed in the first year posttransplant are predictive of chronic rejection and renal graft loss. Transplantation 2009;88:568-74. [CrossRef]
  • Cardarelli F, Saidman S, Theruvath T, Tolkoff-Rubin N, Cosimi AB, Pascual M. The problem of late allograft loss in kidney transplantation. Minerva Urol Nefrol 2003;55:1-11.
  • Saidman S. Significance of anti-HLA and donor-specific antibodies in long-term renal graft survival. Transplant Proc 2007;39:744-6. [CrossRef]
  • McKenna RM, Takemoto SK, Terasaki PI. Anti-HLA antibodies after solid organ transplantation. Transplantation 2000;69:319-26. [CrossRef]
  • Fernández-Fresnedo G, Pastor JM, López-Hoyos M, Ruiz JC, Zubimendi JA, Gonzalez-Cotorruelo J, et al. Relationship of donorspecific class-I anti-HLA antibodies detected by ELISA after kidney transplantation on the development of acute rejection and graft survival. Nephrol Dial Transplant 2003;18:990-5. [CrossRef]
  • Terasaki PI, Cai J. Humoral theory of transplantation:further evidence. Curr Opin Immunol 2005;17:541-5. [CrossRef]
  • Terasaki PI. Humoral theory of transplantation. Am J Transplant 2003;3:665-73. [CrossRef]
  • Terasaki PI, Cai J. Human leukocyte antigen antibodies and chronic rejection:from association to causation. Transplantation 2008;86:377-83. [CrossRef]
  • Stastny P, Ring S, Lu C, Arenas J, Han M, Lavingia B. Role of immunoglobulin (Ig)-G and IgM antibodies against donor human leukocyte antigens in organ transplant recipients. Hum Immunol 2009;70:600-4. [CrossRef]
  • Lawson C, Holder AL, Stanford RE, Smith J, Rose ML. Anti-intercellular adhesion molecule-1 antibodies in sera of heart transplant recipients:a role in endothelial cell activation. Transplantation 2005;80:264-71. [CrossRef]
  • Everly MJ, Terasaki PI. Monitoring and treating posttransplant human leukocyte antigen antibodies. Hum Immunol 2009;70:655-9. [CrossRef]
  • Piazza A, Poggi E, Borrelli L, Servetti S, Monaco PI, Buonomo O, et al. Impact of donor-specific antibodies on chronic rejection occurrence and graft loss in renal transplantation:posttransplant analysis using flow cytometric techniques. Transplantation 2001;71:1106-12. [CrossRef]
  • Costa AN, Scolari MP, Iannelli S, Buscaroli A, D’Arcangelo GL, Brando B, et al. The presence of posttransplant HLA-specific IgG antibodies detected by enzyme-linked immunosorbent assay correlates with specific rejection pathologies. Transplantation 1997;63:167-9. [CrossRef]
  • Terasaki PI, McClelland JD. Microdroplet assay of human serum cytotoxins. Nature 1964;204:998-1000. [CrossRef]
  • Olerup O, Zetterquist H. HLA-DR typing by PCR amplification with sequence-specific primers (PCR-SSP) in two hours:An alternative to serological DR typing in clinical practice including donor-recipient matching in cadaveric transplantation. Tissue Antigens 1992;39:225-35. [CrossRef]
  • Cardarelli F, Pascual M, Tolkoff-Rubin N, Delmonico FL, Wong W, Schoenfeld DA, et al. Prevalence and significance of anti-HLA and donor-specific antibodies long-term after renal transplantation. Transpl Int 2005;18:532-40. [CrossRef]
  • Abe M, Kawai T, Futatsuyama K, Tanabe K, Fuchinoue S, Teraoka S, et al. Postoperative production of anti-donor antibody and chronic rejection in renal transplantation. Transplantation 1997;63:1616-9. [CrossRef]
  • Neylan J, de Smet W, Stijlemans B, Brinker K, Gonwa T, Moran J, et al. Detection of clinically relevant antibodies pretransplant and posttransplant with PRA-STAT. Transplant Proc 1997;29:330-2. [CrossRef]
  • Martin S, Dyer PA, Mallick NP, Gokal R, Harris R, Johnson RW. Posttransplant antidonor lymphocytotoxic antibody production in relation to graft outcome. Transplantation 1987;44:50-3. [CrossRef]
  • Deka R, Panigrahi A, Aggarwal SK, Guleria S, Dash SC, Mehta SN, et al. Influence of pretransplant panel reactive antibodies on the posttransplant sensitization status. Transplant Proc 2002;34:3082-3. [CrossRef]
  • Fritsche L, Hoerstrup J, Budde K, Reinke P, Neumayer H, Frei U, et al. Accurate prediction of kidney allograft outcome based on creatinine course in the first 6 months posttransplant.Transplant Proc 2005;37:731-3. [CrossRef]
  • Süsal C, Opelz G. Kidney graft failure and presensitization against HLA class I and class II antigens. Transplantation 2002;73:1269-73. [CrossRef]
  • Patel R, Terasaki PI. Significance of the crossmatch test in kidney transplantation. N Engl J Med 1968;280:735. [CrossRef]
  • Lee PC, Terasaki PI, Takemoto SK, Lee PH, Hung CJ, Chen YL, et al. All chronic rejection failures of kidney transplants were preceded by the development of HLA antibodies.Transplantation 2002;74:1192-4. [CrossRef]
  • Utzig MJ, Blümke M, Wolff-Vorbeck F, Lang H, Kirste G. Flow cytometry crossmatch. Transplantation 1997;63:551-4. [CrossRef]
  • Smith RN, Kawai T, Boskovic S, Nadazdin O, Sachs DH, Cosimi AB, et al. Four stages and lack of stable accommodation in chronic alloantibody-mediated renal allograft rejection in Cynomolgus monkeys. Am J Transplant 2008;8:1662-72. [CrossRef]
  • Suciu-Foca N, Reed E, D’Agati VD, Ho E, Cohen DJ, Benvenisty AI, et al. Soluble HLA antigens, anti-HLA antibodies, and antiidiotypic antibodies in the circulation of renal transplant recipients. Transplantation 1991;51:593-601. [CrossRef]
  • Schönemann C, Groth J, Leverenz S, May G. HLA class I and class II antibodies:monitoring before and after kidney transplantation and their clinical relevance. Transplantation 1998;65:1519-23. [CrossRef]
  • Müller-Steinhardt M, Fricke L, Kirchner H, Hoyer J, Klüter H. Monitoring of anti-HLA class I and II antibodies by flow cytometry in patients after first cadaveric kidney transplantation. Clin Transplant 2000;14:85-9. [CrossRef]

Long-Term Effects of Antibodies Against Human Leukocyte Antigens Detected by Flow Cytometry in the First Year After Renal Transplantation

Yıl 2013, Cilt: 2013 Sayı: 1, 37 - 45, 01.01.2013
https://doi.org/10.5152/balkanmedj.2012.071

Öz

Kaynakça

  • Mihaylova A, Baltadjieva D, Boneva P, Ivanova M, Penkova K, Marinova D, et al. Clinical relevance of anti-HLA antibodies detected by flow-cytometry bead-based assays--single-center experience. Hum Immunol 2006;67:787-94. [CrossRef]
  • Panigrahi A, Gupta N, Siddiqui JA, Margoob A, Bhowmik D, Guleria S, et al. Post- transplant development of MICA and antiHLA antibodies is associated with acute rejection episodes and renal allograft loss. Hum Immunol 2007;68:362-7. [CrossRef]
  • Van der Mast BJ, van Besouw NM, Witvliet MD, de Kuiper P, Smak Gregoor P, van Gelder T, et al. Formation of donorspecific human leukocyte antigen antibodies after kidney transplantation:correlation with acute rejection and tapering of immunosuppression. Transplantation 2003;75:871-7. [CrossRef]
  • Lee PC, Zhu L, Terasaki PI, Everly MJ. HLA-specific antibodies developed in the first year posttransplant are predictive of chronic rejection and renal graft loss. Transplantation 2009;88:568-74. [CrossRef]
  • Cardarelli F, Saidman S, Theruvath T, Tolkoff-Rubin N, Cosimi AB, Pascual M. The problem of late allograft loss in kidney transplantation. Minerva Urol Nefrol 2003;55:1-11.
  • Saidman S. Significance of anti-HLA and donor-specific antibodies in long-term renal graft survival. Transplant Proc 2007;39:744-6. [CrossRef]
  • McKenna RM, Takemoto SK, Terasaki PI. Anti-HLA antibodies after solid organ transplantation. Transplantation 2000;69:319-26. [CrossRef]
  • Fernández-Fresnedo G, Pastor JM, López-Hoyos M, Ruiz JC, Zubimendi JA, Gonzalez-Cotorruelo J, et al. Relationship of donorspecific class-I anti-HLA antibodies detected by ELISA after kidney transplantation on the development of acute rejection and graft survival. Nephrol Dial Transplant 2003;18:990-5. [CrossRef]
  • Terasaki PI, Cai J. Humoral theory of transplantation:further evidence. Curr Opin Immunol 2005;17:541-5. [CrossRef]
  • Terasaki PI. Humoral theory of transplantation. Am J Transplant 2003;3:665-73. [CrossRef]
  • Terasaki PI, Cai J. Human leukocyte antigen antibodies and chronic rejection:from association to causation. Transplantation 2008;86:377-83. [CrossRef]
  • Stastny P, Ring S, Lu C, Arenas J, Han M, Lavingia B. Role of immunoglobulin (Ig)-G and IgM antibodies against donor human leukocyte antigens in organ transplant recipients. Hum Immunol 2009;70:600-4. [CrossRef]
  • Lawson C, Holder AL, Stanford RE, Smith J, Rose ML. Anti-intercellular adhesion molecule-1 antibodies in sera of heart transplant recipients:a role in endothelial cell activation. Transplantation 2005;80:264-71. [CrossRef]
  • Everly MJ, Terasaki PI. Monitoring and treating posttransplant human leukocyte antigen antibodies. Hum Immunol 2009;70:655-9. [CrossRef]
  • Piazza A, Poggi E, Borrelli L, Servetti S, Monaco PI, Buonomo O, et al. Impact of donor-specific antibodies on chronic rejection occurrence and graft loss in renal transplantation:posttransplant analysis using flow cytometric techniques. Transplantation 2001;71:1106-12. [CrossRef]
  • Costa AN, Scolari MP, Iannelli S, Buscaroli A, D’Arcangelo GL, Brando B, et al. The presence of posttransplant HLA-specific IgG antibodies detected by enzyme-linked immunosorbent assay correlates with specific rejection pathologies. Transplantation 1997;63:167-9. [CrossRef]
  • Terasaki PI, McClelland JD. Microdroplet assay of human serum cytotoxins. Nature 1964;204:998-1000. [CrossRef]
  • Olerup O, Zetterquist H. HLA-DR typing by PCR amplification with sequence-specific primers (PCR-SSP) in two hours:An alternative to serological DR typing in clinical practice including donor-recipient matching in cadaveric transplantation. Tissue Antigens 1992;39:225-35. [CrossRef]
  • Cardarelli F, Pascual M, Tolkoff-Rubin N, Delmonico FL, Wong W, Schoenfeld DA, et al. Prevalence and significance of anti-HLA and donor-specific antibodies long-term after renal transplantation. Transpl Int 2005;18:532-40. [CrossRef]
  • Abe M, Kawai T, Futatsuyama K, Tanabe K, Fuchinoue S, Teraoka S, et al. Postoperative production of anti-donor antibody and chronic rejection in renal transplantation. Transplantation 1997;63:1616-9. [CrossRef]
  • Neylan J, de Smet W, Stijlemans B, Brinker K, Gonwa T, Moran J, et al. Detection of clinically relevant antibodies pretransplant and posttransplant with PRA-STAT. Transplant Proc 1997;29:330-2. [CrossRef]
  • Martin S, Dyer PA, Mallick NP, Gokal R, Harris R, Johnson RW. Posttransplant antidonor lymphocytotoxic antibody production in relation to graft outcome. Transplantation 1987;44:50-3. [CrossRef]
  • Deka R, Panigrahi A, Aggarwal SK, Guleria S, Dash SC, Mehta SN, et al. Influence of pretransplant panel reactive antibodies on the posttransplant sensitization status. Transplant Proc 2002;34:3082-3. [CrossRef]
  • Fritsche L, Hoerstrup J, Budde K, Reinke P, Neumayer H, Frei U, et al. Accurate prediction of kidney allograft outcome based on creatinine course in the first 6 months posttransplant.Transplant Proc 2005;37:731-3. [CrossRef]
  • Süsal C, Opelz G. Kidney graft failure and presensitization against HLA class I and class II antigens. Transplantation 2002;73:1269-73. [CrossRef]
  • Patel R, Terasaki PI. Significance of the crossmatch test in kidney transplantation. N Engl J Med 1968;280:735. [CrossRef]
  • Lee PC, Terasaki PI, Takemoto SK, Lee PH, Hung CJ, Chen YL, et al. All chronic rejection failures of kidney transplants were preceded by the development of HLA antibodies.Transplantation 2002;74:1192-4. [CrossRef]
  • Utzig MJ, Blümke M, Wolff-Vorbeck F, Lang H, Kirste G. Flow cytometry crossmatch. Transplantation 1997;63:551-4. [CrossRef]
  • Smith RN, Kawai T, Boskovic S, Nadazdin O, Sachs DH, Cosimi AB, et al. Four stages and lack of stable accommodation in chronic alloantibody-mediated renal allograft rejection in Cynomolgus monkeys. Am J Transplant 2008;8:1662-72. [CrossRef]
  • Suciu-Foca N, Reed E, D’Agati VD, Ho E, Cohen DJ, Benvenisty AI, et al. Soluble HLA antigens, anti-HLA antibodies, and antiidiotypic antibodies in the circulation of renal transplant recipients. Transplantation 1991;51:593-601. [CrossRef]
  • Schönemann C, Groth J, Leverenz S, May G. HLA class I and class II antibodies:monitoring before and after kidney transplantation and their clinical relevance. Transplantation 1998;65:1519-23. [CrossRef]
  • Müller-Steinhardt M, Fricke L, Kirchner H, Hoyer J, Klüter H. Monitoring of anti-HLA class I and II antibodies by flow cytometry in patients after first cadaveric kidney transplantation. Clin Transplant 2000;14:85-9. [CrossRef]
Toplam 32 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Sağlık Kurumları Yönetimi
Bölüm Makaleler
Yazarlar

Tülay Kılıçaslan Ayna Bu kişi benim

Yaşar Çalışkan Bu kişi benim

Yaşar Çalışkan Bu kişi benim

Hayriye Şentürk Çiftçi Bu kişi benim

Aydın Türkmen Bu kişi benim

Mehmet Gürtekin Bu kişi benim

Yayımlanma Tarihi 1 Ocak 2013
Yayımlandığı Sayı Yıl 2013 Cilt: 2013 Sayı: 1

Kaynak Göster

APA Ayna, T. K., Çalışkan, Y., Çalışkan, Y., Çiftçi, H. Ş., vd. (2013). Long-Term Effects of Antibodies Against Human Leukocyte Antigens Detected by Flow Cytometry in the First Year After Renal Transplantation. Balkan Medical Journal, 2013(1), 37-45. https://doi.org/10.5152/balkanmedj.2012.071
AMA Ayna TK, Çalışkan Y, Çalışkan Y, Çiftçi HŞ, Türkmen A, Gürtekin M. Long-Term Effects of Antibodies Against Human Leukocyte Antigens Detected by Flow Cytometry in the First Year After Renal Transplantation. Balkan Medical Journal. Ocak 2013;2013(1):37-45. doi:10.5152/balkanmedj.2012.071
Chicago Ayna, Tülay Kılıçaslan, Yaşar Çalışkan, Yaşar Çalışkan, Hayriye Şentürk Çiftçi, Aydın Türkmen, ve Mehmet Gürtekin. “Long-Term Effects of Antibodies Against Human Leukocyte Antigens Detected by Flow Cytometry in the First Year After Renal Transplantation”. Balkan Medical Journal 2013, sy. 1 (Ocak 2013): 37-45. https://doi.org/10.5152/balkanmedj.2012.071.
EndNote Ayna TK, Çalışkan Y, Çalışkan Y, Çiftçi HŞ, Türkmen A, Gürtekin M (01 Ocak 2013) Long-Term Effects of Antibodies Against Human Leukocyte Antigens Detected by Flow Cytometry in the First Year After Renal Transplantation. Balkan Medical Journal 2013 1 37–45.
IEEE T. K. Ayna, Y. Çalışkan, Y. Çalışkan, H. Ş. Çiftçi, A. Türkmen, ve M. Gürtekin, “Long-Term Effects of Antibodies Against Human Leukocyte Antigens Detected by Flow Cytometry in the First Year After Renal Transplantation”, Balkan Medical Journal, c. 2013, sy. 1, ss. 37–45, 2013, doi: 10.5152/balkanmedj.2012.071.
ISNAD Ayna, Tülay Kılıçaslan vd. “Long-Term Effects of Antibodies Against Human Leukocyte Antigens Detected by Flow Cytometry in the First Year After Renal Transplantation”. Balkan Medical Journal 2013/1 (Ocak 2013), 37-45. https://doi.org/10.5152/balkanmedj.2012.071.
JAMA Ayna TK, Çalışkan Y, Çalışkan Y, Çiftçi HŞ, Türkmen A, Gürtekin M. Long-Term Effects of Antibodies Against Human Leukocyte Antigens Detected by Flow Cytometry in the First Year After Renal Transplantation. Balkan Medical Journal. 2013;2013:37–45.
MLA Ayna, Tülay Kılıçaslan vd. “Long-Term Effects of Antibodies Against Human Leukocyte Antigens Detected by Flow Cytometry in the First Year After Renal Transplantation”. Balkan Medical Journal, c. 2013, sy. 1, 2013, ss. 37-45, doi:10.5152/balkanmedj.2012.071.
Vancouver Ayna TK, Çalışkan Y, Çalışkan Y, Çiftçi HŞ, Türkmen A, Gürtekin M. Long-Term Effects of Antibodies Against Human Leukocyte Antigens Detected by Flow Cytometry in the First Year After Renal Transplantation. Balkan Medical Journal. 2013;2013(1):37-45.