Relevance of MICA Alleles Matching Rate and Posttransplant Rejection in Clinical LRD Organ Transplantations
Author(s)
Liang He1,
Gang Ji2,
Zhang Zhang2,
Chunsheng Xu2,
Weizhong Wang2,
Boquan Jin2,
Guanglong Dong3*
Affiliation(s)
1 Department of General Surgery, Lanzhou Military District Hospital in Urumqi, Urumqi, China. 2 Department of Gastrointestinal Surgery, State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, China. 3 Department of General Surgery, The General Hospital of the People’s Liberation Army, Beijing, China.
1 Department of General Surgery, Lanzhou Military District Hospital in Urumqi, Urumqi, China. 2 Department of Gastrointestinal Surgery, State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, China. 3 Department of General Surgery, The General Hospital of the People’s Liberation Army, Beijing, China.
ABSTRACT
Objective: Recipients usually undergo posttransplant rejection in HLA-identical transplantations. Recent studies have shown that MHC class I related chain A (MICA) has been found to be associated with allograft survival. The goal of this study is to investigate the correlation between matching rate of MICA alleles and posttransplant rejection in clinical living related donor transplantation (LRD) organ transplantations. Methods: Twenty pairs of blood samples were detected for HLA/MICA matching through polymerase chain reaction with sequence specific primers and for anti-MICA Abs using Luminex. At the same time, pathologic biopsies of all recipients were diagnosed and classified into different levels by the unified standard. Univariate Spearman’s analysis was established. Log-Rank analysis was performed twice, and Kaplan-Meier survival curves were generated to assess the relationship between MICA matching rates and posttransplant rejection in living-related donor transplantations. Results-The result showed that HLA matching of all recipients and donors were identical, whereas MICA matching was not. There was statistical difference between pathological classification and survival (P < 0.05). The development of Abs to MICA was strongly associated with posttransplant rejection. Conclusions: Recipients with higher MICA matching rates with their donors had lower pathologic classifications and were more likely to survive longer. Lower graft survival and more rejection episodes were observed among recipients with lower MICA matching rates with donors. Aside from HLA matching, the MICA matching rate could be an important prognostic index for LRD transplantations.
KEYWORDS
MHC, HLA, MHC Class I Related Chain A (MICA), Polymerase Chain Reaction (PCR), Living Related Donor Transplantation (LRD)
MHC, HLA, MHC Class I Related Chain A (MICA), Polymerase Chain Reaction (PCR), Living Related Donor Transplantation (LRD)
Cite this paper
He, L. , Ji, G. , Zhang, Z. , Xu, C. , Wang, W. , Jin, B. and Dong, G. (2015) Relevance of MICA Alleles Matching Rate and Posttransplant Rejection in Clinical LRD Organ Transplantations. International Journal of Clinical Medicine, 6, 33-43. doi: 10.4236/ijcm.2015.61005.
He, L. , Ji, G. , Zhang, Z. , Xu, C. , Wang, W. , Jin, B. and Dong, G. (2015) Relevance of MICA Alleles Matching Rate and Posttransplant Rejection in Clinical LRD Organ Transplantations. International Journal of Clinical Medicine, 6, 33-43. doi: 10.4236/ijcm.2015.61005.
References
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[1] Sumitran, H.S. (2008) Relevance of MICA and Other Non-HLA Antibodies in Clinical Transplantation. Current Opinion in Immunology, 20, 607-613. http://dx.doi.org/10.1016/j.coi.2008.07.005 [2] Opelz, G. (2005) Non-HLA-Transplantation Immunity Revealed by Lymphocytotoxic Antibodies. Lancet, 365, 1570-1576. http://dx.doi.org/10.1016/S0140-6736(05)66458-6 [3] Panigrahi, A., Gupta, N., Siddiqui, J.A., et al. (2007) Post Transplant Development of MICA and Anti-HLA Antibodies Is Associated with Acute Rejection Episodes and Renal Allograft Loss. Human Immunology, 68, 362-367.
http://dx.doi.org/10.1016/j.humimm.2007.01.006 [4] Bahram, S., Bresnahan, M., Geraghty, D.E. and Spies, T. (1994) A Second Lineage of Mammalian Major Histocompatibility Complex Class I Genes. The Proceedings of the National Academy of Sciences of the United States of America, 91, 6259-6263. http://dx.doi.org/10.1073/pnas.91.14.6259 [5] Petersdorf, E.W., Shuler, K.B., Longton, G.M., Spies, T. and Hansen, J.A. (1999) Population Study of Allelic Diversity in the Human MHC Class I-Related MIC-A Gene. Immunogenetics, 49, 605-612.
http://dx.doi.org/10.1007/s002510050655 [6] Zwirner, N.W., Marcos, C.Y., Mirbaha, F., Zou, Y. and Stastny, P. (2000) Identification of MICA as a New Polymorphic Alloantigen Recognized by Antibodies in Sera of Organ Transplant Recipients. Human Immunology, 61, 917-924.
http://dx.doi.org/10.1016/S0198-8859(00)00162-2 [7] Zwirner, N.W., Fernandez-Vina, M.A. and Stastny, P. (1998) MICA, a New Polymorphic HLA-Related Antigen, Is Expressed Mainly by Keratinocytes, Endothelial Cells, and Monocytes. Immunogenetics, 47, 139-148.
http://dx.doi.org/10.1007/s002510050339 [8] Clatworthy, M., Espeli, M., Torpey, N. and Smith, K. (2010) The Generation and Maintenance of Serum Alloantibody. Current Opinion in Immunology, 22, 669-681. http://dx.doi.org/10.1016/j.coi.2010.08.018 [9] Choy, M.K. and Phipps, M.E. (2010) MICA Polymorphism: Biology and Importance in Immunity and Disease. Trends in Molecular Medicine, 16, 97-106. http://dx.doi.org/10.1016/j.molmed.2010.01.002 [10] Sumitran, H.S., Wilczek, H.E., Holgersson, J. and Soderstrom, K. (2002) Identification of the Nonclassical HLA Molecules, Mica, as Targets for Humoral Immunity Associated with Irreversible Rejection of Kidney Allografts. Transplantation, 74, 268-277. http://dx.doi.org/10.1097/00007890-200207270-00019 [11] Li, L., Wadia, P., Chen, R., Kambham, N., Naesens, M., Sigdel, T.K., et al. (2009) Identifying Compartment-Specific Non-HLA Targets after Renal Transplantation by Integrating Transcriptome and “Antibodyome” Measures. Proceedings of the National Academy of Sciences of the United States of America, 106, 4148-4153.
http://dx.doi.org/10.1073/pnas.0900563106 [12] Dragun, D. and Hegner, B. (2009) Non-HLA Antibodies Post-Transplantation: Clinical Relevance and Treatment in Solid Organ Transplantation. Contributions to Nephrology, 162, 129-139. http://dx.doi.org/10.1159/000170845 [13] Mizutani, K., Terasaki, P., Rosen, A., Esquenazi, V., Miller, J., Shih, R.N.J., et al. (2005) Serial Ten-Year Follow-Up of HLA and MICA Antibody Production Prior to Kidney Graft Failure. American Journal of Transplantation, 5, 2265-2272. http://dx.doi.org/10.1111/j.1600-6143.2005.01016.x [14] Ormonde, D.G., De-Boer, W.B., Kierath, A., Bell, R., Shilkin, K.B., House, A.K., et al. (1999) Banff Schema for Grading Liver Allograft Rejection: Utility in Clinical Practice. Liver Transplantation and Surgery, 5, 261-268.
http://dx.doi.org/10.1002/lt.500050418 [15] Solez, K., Axelsen, R.A., Benediktsson, H., Burdick, J.F., Cohen, A.H., Colvin, R.B., et al. (1993) International Standardization of Criteria for the Histologic Diagnosis of Renal Allograft Rejection: The Banff Working Classification of Kidney Transplant Pathology. Kidney International, 44, 411-421. http://dx.doi.org/10.1038/ki.1993.259 [16] Paramesh, A.S., Zhang, R., Baber, J., Yau, C.L., Slakey, D.P., Killackey, M.T., et al. (2010) The Effect of HLA Mismatch on Highly Sensitized Renal Allograft Recipients. Clinical Transplantation, 24, E247-E252.
http://dx.doi.org/10.1111/j.1399-0012.2010.01306.x [17] Panigrahi, A., Deka, R., Bhowmik, D., Tiwari, S.C. and Mehra, N.K. (2004) Immunological Monitoring of Posttrans-plant Allograft Sensitization Following Living Related Donor Renal Transplantation. Transplantation Proceedings, 36, 1336-1339. http://dx.doi.org/10.1016/j.transproceed.2004.05.072 [18] Hourmant, M., Cesbron, G.A., Terasaki, P.I., Mizutani, K., Moreau, A., Meurette, A., et al. (2005) Frequency and Clinical Implications of the Development of Donor-Specific and Non-Donor-Specific HLA Antibodies after Kidney Transplantation. Journal of the American Society of Nephrology, 16, 2804-2812.
http://dx.doi.org/10.1681/ASN.2004121130 [19] Terasaki, P.I., Ozawa, M. and Castro, R. (2007) Four-Year Follow-Up of a Prospective Trial of HLA and MICA Antibodies on Kidney Graft Survival. American Journal of Transplantation, 7, 408-415.
http://dx.doi.org/10.1111/j.1600-6143.2006.01644.x [20] Stastny, P., Zou, Y., Fan, Y., Qin, Z. and Lavingia, B. (2009) The Emerging Issue of MICA Antibodies: Antibodies to MICA and Other Antigens of Endothelial Cells. Contributions to Nephrology, 162, 99-106.
http://dx.doi.org/10.1159/000170842 [21] Kauke, T., Kaczmarek, I., Dick, A., Schmoeckel, M., Deutsch, M.A., Beiras-Fernandez, A., et al. (2009) Anti-MICA Antibodies Are Related to Adverse Outcome in Heart Transplant Recipients. Journal of Heart and Lung Transplantation, 28, 305-311. http://dx.doi.org/10.1016/j.healun.2009.01.003 [22] Fodil, N., Laloux, L., Wanner, V., Pellet, P., Hauptmann, G., Mizuki, N., et al. (1996) Allelic Repertoire of the Human MHC Class IMICA Gene. Immunogenetics, 44, 351-357. http://dx.doi.org/10.1007/BF02602779 [23] Hankey, K.G., Drachenberg, C.B., Papadimitriou, J.C., Klassen, D.K., Philosophe, B., Bartlett, S.T., et al. (2002) MIC Expression in Renal and Pancreatic Allografts. Transplantation, 73, 304-306.
http://dx.doi.org/10.1097/00007890-200201270-00029 [24] Zafar, M.N., Terasaki, P.I., Naqvi, S.A. and Rizvi, S.A. (2006) Non-HLA Antibodies after Rejection of HLA Identical Kidney Transplants. Clinical Transplants, 421-426. [25] Zou, Y. and Stastny, P. (2009) The Role of Major Histocompatibility Complex Class I Chain-Related Gene A Antibodies in Organ Transplantation. Current Opinion in Organ Transplantation, 14, 414-418.
http://dx.doi.org/10.1097/MOT.0b013e32832d835e [26] Kitcharoen, K., Witt, C.S., Romphruk, A.V., Christiansen, F.T. and Leelayuwat, C. (2006) MICA, MICB, and MHC Beta Block Matching in Bone Marrow Transplantation: Relevance to Transplantation Outcome. Human Immunology, 67, 238-246. http://dx.doi.org/10.1016/j.humimm.2006.02.012