| As is known to all, end-stage renal disease(ESRD) is the most effective way of replacement therapy for renal transplantation allografts, many factors influence the prognosis of renal transplantation and long-term survival among them, and acute rejection (AR) is one of the most important factors, and the hotspot. ABO blood group antigens and human histocompatibility antigen (HLA) gene are producted in recent years, researchers recognize that the cause of organ transplant rejection, the latter antibody involved in the humoral immune response is the main cause of acute renal allograft rejection reaction(AR), however, pre-transplant recipient body for the donor-specific antibodies even lead to hyperacute rejection. As it was found that detection of anti-HLA antibodies and the emergence of new immunosuppressive, the incidence of the hyperacute rejection and acute rejection (AR) greatly reduced.The clinical study found that even in human histocompatibility antigen (HLA) matching the good situation, the acute renal allograft rejection (AR) may still occur. People began to realize there may be non-HLA antibodies can mediate involved in rejection. In1994, Tom Spies, Professor, Research Center of Seattle University, his team first found there was a MHC-I gene family in the HLA class-Ⅲ gene region, named major histocompatibility complex class I-related chain A,MIC genes. According to their molecular structure and function, it included MICA, MICB, MICC, MICD, MICE and MICF, in addition to MICA and MICB involved in coding for functional genes, expression and transcription, the others were pseudo genes. MICA is located in the HLA-B sites upstream of about46kb, full-length11722bp, encoding the1382bp transcription child, because of HLA-neighboring B gene, the product of their genes encoding is similar with HLA-I molecules. The entire gene, including the six exons encoding the L leader peptide, extracellular of al, a2and a3domain, the transmembrane and cytoplasm. It is different from that of HLA-class la genes is characterized by:a length of6840bp intron between L leader peptide exon2; after a long intron in the transmembrane region; cytoplasmic3’-untranslated region of integration in an exon. MICA gene is highly polymorphic and61alleles has been reported. Depending on the encoding transmembrane region of DNA sequence microsatellite GCT repetitions, in the microsatellite genotypes of MICA transmembrane region of A4, A5, A5.1, A6, A7, and A10have been found. Due to the different races, even between different ethnic groups in the same race, MICA allele distribution is different. Ribas found that the beating of Afro-Brazilian common MICA alleles were MICA*00801, MICA*00201, MICA*00901. Lucas found the most common MICA alleles in other southeastern Spain crowd was MICA*008. The Asian population of MICA alleles were MICA*002, MICA*004, MICA*008, MICA*007, MICA*010, MICA*017and MICA*049. This polymorphism may result in allogeneic organ transplantation, under normal circumstances do not express the epithelial cells of MICA expression after transplantation and cause transplant humoral rejection. Combination of MIC genes encode molecules and NKG2D molecules, not with the T cell receptor (TCR) of the combination, not connected with the β2-microglobulin, not combined with the peptide, and they also do not make interferon expression raised. HLA-Class I molecules are widely distributed in human cells, but MICA is abundantly expressed in the endothelial cells, dendritic cells, the surface of the fiber cells and tumor cells, but in T-B cell surface don’t express, as well as in normal kidney and pancreas, but when transplant rejection occurred, MICA were express in the graft epithelium, and the local cell, tissue damaged. In2002, the Hankey found the MICA gene express in all acute tubular necrosis (ATN) and acute rejection (AR) in kidney tissue detected by immunohistochemical methods, The results show that, MICA antibodies were closely related with transplant rejection. To mind the relationship of anti-HLA antibodies and rejection, people are also interested in its sensitization pathway. Patients with the panel of reactive antibody (PRA) were produced through the transplant, blood transfusion, pregnancy and other contact with the human major histocompatibility antigen (MHC) has been sensitized, the existence in the peripheral blood of anti-HLA antibodies and graft acute rejection, chronic rejection, delayed graft function (DGF), graft survival is closely related. However, the complement dependent cytotoxicity test (CDC) can not detect MICA antibodies before kidney transplantation. Meantime, MICA antibodies produced by sensitized pathway is not yet fully clear, a few studies were reported about the relationship of the sensitized pathway and acute renal allograft rejection (AR). Therefore, this subject, according to the MICA antibodies generated way, understand the type of immunoglobulin, thus further study of acute rejection (AR) reversion of IgM-MICA antibodies and IgM&IgG complex MICA antibodies after renal transplantation.Objective:To investigate the MICA antibody sensitization pathway, and analyze the type of immunoglobulin. Methods:Choose197patients in our hospital waiting undergoing kidney transplant surgery between December2007and January2011, using Luminex200liquid chip technique test MICA antibodies and their specificity, the total number of experiments241times. MICA antigen were preparaed by the Texas and Southwestern University Internal Medicine Laboratory Professor Zou,. The package contained11kinds of MICA antigens, MICA*001,002,004,006,007,008,009,012,017,018and019. Collect the above-mentioned renal transplant recipients age, gender, primary disease, dialysis, blood transfusion, pregnancy history, transplant history, and clinical data.Results:197cases of renal transplant recipients, MICA antibody-positive was45cases, the positive rate was22.84%, including35cases can detect the specific antibodies,10cases were positive screening, a single specific antibody for18cases, more specific antibodies17cases, the highest frequency was MICA*019.157cases can be collected clinical data in197renal transplant recipients, including45positive MICA antibody recipients. Among157cases,89recipients had no blood transfusion, pregnancy, transplantation history, that is known allergens inexperienced by those, including MICA antibody-positive for26cases (29.21%), the type of immunoglobulin is IgM; a history of blood transfusion, pregnancy, transplantation history (three allergens history of at least one), that is known allergens experienced by68cases, including MICA antibody-positive recipients for19cases (27.94%), the type of immunoglobulin is IgM&IgG complex; MICA antibody-positive rate between the two groups of recipients was not statistically significant (P>0.05).45patients with MICA antibodies in26cases who had no blood transfusion,pregnancy, transplantation experience (57.78%);19cases had experienced previous known one or more allergens (42.22%).Conclusion:he positive rate of MICA antibodies in preoperative renal transplant recipients in this study was22.84%, the frequency of a single specific antibody is quite similar with the frequency of a variety of specific antibodies. There is no significant difference between whether had previous blood transfusion, pregnancy, transplant sensitization experience and the generation of the MICA antibodies in renal transplant recipients. That is to say that the same lead to the generation of MICA antibodies without the above-mentioned allergens.Objective:Depending on the type of immunoglobulin, explore the impact of renal transplant recipients with postoperative acute rejection (AR), treatment and reversal in different ways to produce MICA antibodies.Methods:Select all the45cases of MICA antibody-positive renal transplant recipients, collect the clinical data contained drug immunosuppressant program, acute rejection (AR),and its reversal program in post-kidney transplant recipients. Produce different types of channels and immunoglobulin, divided into IgM-MICA antibody group and the IgM&IgG complex MICA antibody groups, analysis the occurrence of acute rejection in renal transplantation, treatment and outcome of the situation between them.Results:38in45MICA antibody-positive patients undergoing renal transplantation, including22cases had previously sensitized experience, the type of MICA antibodies immunoglobulin is IgM,7cases occur acute rejection (AR)(31.8%),after high-dose methylprednisolone (MP) pulse therapy for3to5days, all caught the smooth reversal (100%);16cases had history of blood transfusion, pregnancy, transplantation, the type MICA antibodies of immunoglobulin is IgM&IgG complex,7cases occur acute rejection (AR)(43.8%),after high-dose methylprednisolone(MP) pulse therapy for3to5days,3cases were successfully reversed (42.9%), the remaining four cases were treated by methylprednisolone (MP) and cyclophosphamide pulse therapy and hemodialysis transitional had not been reversed. A32-year-old male recipient, after the first transplant, urine output has been maintained in3000～4000ml/day, but serum creatinine remained at700～800umol/L, by methylprednisolone, cyclophosphamide pulse therapy and hemodialysis transition, the serum creatinine has not yet decreased. One month later, he accepted renal transplantation again and removed the original transplanted kidney suggest acute interstitial rejection by biopsy. After twice renal transplantation, the recipient’s urine output remained at2000～3500ml/day, four days later, serum creatinine fell to184umol/L, the fifth day, serum creatinine gradually increased, by methylprednisolone, cyclophosphamide pulse therapy and hemodialysis transition, the serum creatinine has not yet decreased, the reversal failed again, and now has been hemodialysis replacement therapy. PRA were negative between the preoperative and postoperative, MICA antibody specificity MICA27,09,04. These data suggested the incidence of AR were not associational with the two immunoglobulin types of MICA antibodies (X2=0.567, P=0.452>0.05), but the reversal rate of AR were significantly different from them (X2=5.6, P=0.018<0.05).Conclusion:MICA antibody was produced from the different route, there is,no significant difference in the occurrence of different types of immunoglobulin and acute rejection (AR). The incidence of acute rejection (AR) between IgM-MICA antibodies and IgM&IgG complex MICA recipients is similar. However, the outcome of both is not similar. The recipient with IgM-MICA antibodies by the reversal effect of acute rejection was significantly better, and the treatment is simple and effective. As forward-looking, we need to pay attention to the existence of IgG-MICA antibodies sensitized by the history of blood transfusion, pregnancy, transplantation, experience before transplantation in renal transplant recipients. In clinical work, clinicians can ask MICA antibodies recipients’sensitized experience so that understand the MICA antibody production channels and the type of immunoglobulin... |
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