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Detection of Anti-HLA Antibodies Produced After Transplantation in Renal Transplants and Evaluation of Its Association with the Other Parameters

Year 2018, Volume: 25 Issue: 4, 385 - 392, 01.12.2018
https://doi.org/10.17343/sdutfd.363352

Abstract

Aim: In this study,
it was aimed to evaluate the immunological response to graft and its
association with related factors in the sera samples collected periodically
from patients transplanted from deceased or alive donors in Izmir Tepecik
Education and Research Hospital.

Material and Method: Anti-HLA
antibody screening and identification tests of 31 patient sera samples were
performed by flow cytometric method. The sera samples were collected
periodically (1st day, 1st week, 2nd week, 4th
week, 12th week, 24th week and 52nd week)
after transplantations in our hospital. After the screening of all samples, anti-HLA
antibodies of PRA positive samples were identified. All of procedures were performed
according to the manufacturer’s instructions. The other parameters were statistically
evaluated by Pearson correlation test.

Results: Of the
patients, 12.9% and 6.45% were only class I and II positive in the
post-transplant 52nd week, respectively. None of the patients was
class I and II positive. It was found that antibodies were not produced against
mismatched antigens on the 1st day, 1st, 2nd, 4th, and 12th
weeks after transplantation. The antibodies were produced 24 weeks after
transplantation in some cases. However, the results could not be evaluated
statistically because of the small patient group. There were statistically
significant correlations between last creatinine levels-donor ages and GFR
values-patient ages (p<0.001, p<0.01, respectively), whereas there was no
significant association between antibody production and creatinine levels.  







Conclusion: It was
observed that anti-HLA antibodies were produced before transplantation in a
patient with pre-transplant blood transfusion. The antibodies were produced in
24th week in five patients. Therefore, anti-HLA antibody screening
tests to be performed on the 12th week after transplantation may be important
for the treatment protocol.

References

  • Lowe D, Higgins R, Zehnder D, Briggs DC. Significant IgG subclass heterogeneity in HLA-specific antibodies: Implications for pathogenicity, prognosis, and the rejection response. Hum Immunol 2013;74(5): 666-672.
  • McMurtrey C, Lowe D, Buchli R, Daga S, Royer D, Humphrey A, et al. Profiling antibodies to class II HLA in transplant patient sera. Hum Immunol 2014; 75(3): 261-270.
  • Ishida H, Hirai T, Kohei N, Yamaguchi Y, Tanabe K. Significance of qualitative and quantitative evaluations of anti-HLA antibodies in kidney transplantation. Transplant Int 2011; 24(2): 150-7.
  • Ayna TK, 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 Med J 2013;30(1): 37-45.
  • Kurtulmuş Y, Ayna TK, Soyöz M, Özyılmaz B, Tanrısev M, Afacan G, et al. Comparison of Anti-HLA Antibodies of Kidney Transplant Candidates with Chronic Renal Failure by Two Different Methods: Flow-PRA and Luminex PRA. Transplant Proceed 2013;45(3): 875-877.
  • Pirim I, Soyoz M, Ayna TK, Kocyigit AO, Gurbuz BC, Tugmen C, et al. De novo Produced Anti-Human Leukocyte Antigen Antibodies Relation to Alloimmunity in Patients with Chronic Renal Failure. Genet Test Mol Biomarkers 2015; 19(6): 335-8.
  • Açıkgöz HE, Tüysüz Ö, Sarandöl E, Dirican M. [Comparison of MDRD Formula and Creatinine Clearance in Estimation of Glomerular Filtration Rate]. Tr Biokim Derg 2013;11(1): 21-29.
  • Coronel F, Sanchez-Fructuoso A, Conesa J, Prats D, Barrientos A. Pre-Transplant Treatment Modality and Renal Transplant Outcomes. Dial Transplant 2006;35(8): 1-4.
  • Jordan SC and Vo AA. Donor-specific antibodies in allograft recipients: etiology, impact and therapeutic approaches. Curr Opin Organ Transplant 2014;19(6): 591-597.
  • Zhang Q, Liang LW, Gjertson DW, Lassman C, Wilkinson AH, Kendrick E, et al. Development of Posttransplant Antidonor HLA Antibodies Is Associated with Acute Humoral Rejection and Early Graft Dysfunction. Transplantation 2005;79(5): 591–598.
  • Cardarelli F, Pascual M, Tolkoff-Rubin N, Deşmonico 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(5): 532–540.
  • Takemoto S, Port FK, Claas FHJ, Duquesnoy RJ. HLA Matching for Kidney Transplantation. Hum Immunol 2004;65(12): 1489 –1505.
  • Imamovic S, Ljuca F, Imamovic G, Iljazagic Halilovic F, Krdzalic A, Hasukic S, et al. Influence of Donor Age on Renal Graft Function in the first Seven Post Transplant Days. Bosnian J Basic Med 2010;10(1): 73-77.
  • Baptista APM, Junior HTS, Pestana JOM. Influence of deceased donor hemodynamic factors in transplant recipient renal function. J Bras Nephrol 2013;35(4): 289-298.
  • Lim WH, Chapman JR, Coates PT, Lewis JR, Russ GR, Watson N, et al. HLA-DQ Mismatches and Rejection in Kidney Transplant Recipients. Clin J Am Soc Nephrol 2016;11(5):875-883.
  • Hajeer AH. Panel Reactive Antibody test (PRA) in renal transplantation. Saudi J Kidney Dis Transpl 2006;17(1):1-4.

Böbrek Nakli Olan Hastalarda Nakil Sonrasında Oluşan Anti-HLA Antikorlarının Saptanması ve Çeşitli Parametrelerle İlişkisinin Değerlendirilmesi

Year 2018, Volume: 25 Issue: 4, 385 - 392, 01.12.2018
https://doi.org/10.17343/sdutfd.363352

Abstract

Amaç: Bu çalışmada İzmir
Tepecik Eğitim ve Araştırma Hastanesi’nde kadavra veya canlı donörden böbrek
nakli olmuş hastaların nakil sonrasında periyodik olarak toplanan serum
örneklerinde grefte karşı gelişen immünolojik cevabın ve ilgili faktörlerle
arasındaki ilişkisinin değerlendirilmesi amaçlanmıştır.

Gereç ve Yöntem: 31
hasta serumunun anti-HLA antikor tarama ve tanımlama testleri flow sitometrik
yöntemle yapılmıştır. Bu serum örnekleri, hastanemizde nakilden sonra periyodik
olarak (1. gün, 1. hafta, 2. hafta, 4. hafta, 12. hafta, 24. hafta ve 52.
hafta) toplanmıştır. Bütün örneklere tarama testi yapılırken, sadece PRA
pozitif olan serum örneklerine anti-HLA antikor tipini belirlemek amacıyla
tanımlama testi uygulanmıştır. Bütün prosedürler üretici firmanın talimatlarına
göre yapılmıştır. Diğer parametreler Pearson korelasyon testiyle istatistiksel
oalrak değerlendirilmiştir.

Bulgular: Nakilden sonra
52. haftadan sonra hastaların sırasıyla %12,9 ile %6,45’i anti-HLA sınıf I ve
II antikorları bakımından pozitif bulunmuştur. Hastalarda 1. gün, 1., 2., 4. ve
12. haftalarda mismatch antijenlere karşı antikor oluşumu gözlenmemiştir. Bir
hastada antikorlar 24. haftadan itibaren oluşmuştur. Yapılan korelasyon
analizlerinde hastaların nakil sonrası son kreatinin değerleriyle donör yaşları
ve GFR değerleriyle hasta yaşları arasında istatistiksel olarak anlamlı
sonuçlar elde edilmiştir (sırasıyla p<0.001, p<0.01). Nakil sonrasında de
novo antikor üreten hastaların kreatinin değerleriyle antikor üretimi arasında
ilişki bulunmamıştır (p>0.05).







Sonuç: Nakil öncesinde
kan transfüzyonu olan bir hastada 12. haftada anti-HLA antikoru oluştuğu
görülmüştür. 5 hastada 24. haftadan sonra antikor oluşmuştur. Dolayısıyla nakil
sonrası 12. haftadan itibaren rutinde yapılacak anti-HLA antikoru tarama
testleri tedavi protokolü için önemli olabilir.

References

  • Lowe D, Higgins R, Zehnder D, Briggs DC. Significant IgG subclass heterogeneity in HLA-specific antibodies: Implications for pathogenicity, prognosis, and the rejection response. Hum Immunol 2013;74(5): 666-672.
  • McMurtrey C, Lowe D, Buchli R, Daga S, Royer D, Humphrey A, et al. Profiling antibodies to class II HLA in transplant patient sera. Hum Immunol 2014; 75(3): 261-270.
  • Ishida H, Hirai T, Kohei N, Yamaguchi Y, Tanabe K. Significance of qualitative and quantitative evaluations of anti-HLA antibodies in kidney transplantation. Transplant Int 2011; 24(2): 150-7.
  • Ayna TK, 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 Med J 2013;30(1): 37-45.
  • Kurtulmuş Y, Ayna TK, Soyöz M, Özyılmaz B, Tanrısev M, Afacan G, et al. Comparison of Anti-HLA Antibodies of Kidney Transplant Candidates with Chronic Renal Failure by Two Different Methods: Flow-PRA and Luminex PRA. Transplant Proceed 2013;45(3): 875-877.
  • Pirim I, Soyoz M, Ayna TK, Kocyigit AO, Gurbuz BC, Tugmen C, et al. De novo Produced Anti-Human Leukocyte Antigen Antibodies Relation to Alloimmunity in Patients with Chronic Renal Failure. Genet Test Mol Biomarkers 2015; 19(6): 335-8.
  • Açıkgöz HE, Tüysüz Ö, Sarandöl E, Dirican M. [Comparison of MDRD Formula and Creatinine Clearance in Estimation of Glomerular Filtration Rate]. Tr Biokim Derg 2013;11(1): 21-29.
  • Coronel F, Sanchez-Fructuoso A, Conesa J, Prats D, Barrientos A. Pre-Transplant Treatment Modality and Renal Transplant Outcomes. Dial Transplant 2006;35(8): 1-4.
  • Jordan SC and Vo AA. Donor-specific antibodies in allograft recipients: etiology, impact and therapeutic approaches. Curr Opin Organ Transplant 2014;19(6): 591-597.
  • Zhang Q, Liang LW, Gjertson DW, Lassman C, Wilkinson AH, Kendrick E, et al. Development of Posttransplant Antidonor HLA Antibodies Is Associated with Acute Humoral Rejection and Early Graft Dysfunction. Transplantation 2005;79(5): 591–598.
  • Cardarelli F, Pascual M, Tolkoff-Rubin N, Deşmonico 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(5): 532–540.
  • Takemoto S, Port FK, Claas FHJ, Duquesnoy RJ. HLA Matching for Kidney Transplantation. Hum Immunol 2004;65(12): 1489 –1505.
  • Imamovic S, Ljuca F, Imamovic G, Iljazagic Halilovic F, Krdzalic A, Hasukic S, et al. Influence of Donor Age on Renal Graft Function in the first Seven Post Transplant Days. Bosnian J Basic Med 2010;10(1): 73-77.
  • Baptista APM, Junior HTS, Pestana JOM. Influence of deceased donor hemodynamic factors in transplant recipient renal function. J Bras Nephrol 2013;35(4): 289-298.
  • Lim WH, Chapman JR, Coates PT, Lewis JR, Russ GR, Watson N, et al. HLA-DQ Mismatches and Rejection in Kidney Transplant Recipients. Clin J Am Soc Nephrol 2016;11(5):875-883.
  • Hajeer AH. Panel Reactive Antibody test (PRA) in renal transplantation. Saudi J Kidney Dis Transpl 2006;17(1):1-4.
There are 16 citations in total.

Details

Primary Language English
Subjects Clinical Sciences
Journal Section Research Articles
Authors

Aslı Özkızılcık Koçyiğit

İbrahim Pirim

Tülay Kılıçaslan Ayna

Mustafa Soyöz

Publication Date December 1, 2018
Submission Date December 7, 2017
Acceptance Date March 12, 2018
Published in Issue Year 2018 Volume: 25 Issue: 4

Cite

Vancouver Özkızılcık Koçyiğit A, Pirim İ, Kılıçaslan Ayna T, Soyöz M. Detection of Anti-HLA Antibodies Produced After Transplantation in Renal Transplants and Evaluation of Its Association with the Other Parameters. Med J SDU. 2018;25(4):385-92.

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