Background Good HLA-A, HLA-B, and HLA-DR matches do not guaranteerejection-free renal transplantation. Some kidney transplantsfail despite such matches, suggesting that other antigens mightbe targets for rejection. Major-histocompatibility-complex (MHC)class I–related chain A (MICA) antigens are polymorphicand can elicit antibody production. We sought to determine whetheran immune response to MICA antigens might play a role in thefailure of kidney allografts.
Methods Pretransplantation serum samples from 1910 recipientsof kidney transplants from deceased donors were tested for anti-MICAantibodies with an assay in which single MICA antigens wereattached to polystyrene microspheres.
Results Antibodies against MICA alleles were detected in 217of the 1910 patients (11.4%). The presence of MICA antibodieswas associated with renal-allograft rejection. The mean (±SE)1-year graft-survival rate was 88.3±2.2% among recipientswith anti-MICA antibodies as compared with 93.0±0.6%among recipients without anti-MICA antibodies (P=0.01). Amongrecipients of first kidney transplants, the survival rate waseven lower among MICA antibody–positive patients (87.8±2.4%)than among MICA antibody–negative recipients (93.5±0.6%,P=0.005). In addition, the association of MICA sensitizationwith reduced graft survival was more evident in kidney-transplantrecipients with good HLA matching: among 326 recipients whoreceived well-matched kidneys (0 or 1 HLA-A plus HLA-B plusHLA-DR mismatch), sensitization against MICA was associatedwith poorer allograft survival (83.2±5.8% among thosewith anti-MICA antibodies vs. 95.1±1.3% among those withoutsuch antibodies, P=0.002).
Conclusions Presensitization of kidney-transplant recipientsagainst MICA antigens is associated with an increased frequencyof graft loss and might contribute to allograft loss among recipientswho are well matched for HLA.
Major-histocompatibility-complex (MHC) class I–relatedchain A (MICA) antigens are surface glycoproteins1 with functionsrelated to innate immunity.2,3,4 MICA antigens are expressedon endothelial cells, dendritic cells, fibroblasts, epithelialcells, and many tumors, but not on peripheral-blood lymphocytes.As with the HLA antigens, which MICA antigens resemble onlyremotely in terms of structure, exposure to allogeneic MICAduring transplantation can elicit antibody formation.5 It iswell known that antibodies against HLA antigens, especiallythose recognizing donor antigens, can severely damage kidneyallografts.6 Transplantation performed in the presence of apositive donor cross-match may result in hyperacute vascularrejection.7,8 Antibodies against HLA antigens have also beenassociated with both acute vascular rejection9,10 and chronicrejection.11 Since MICA antigens are not expressed on lymphocytes,12the cells commonly used for cross-matching, antibodies directedagainst MICA are not detected with the methods generally used.However, polymorphic MICA antigens are expressed on endothelialcells12 and have been found to be cytotoxic in the presenceof serum complement,13 so it is likely that such antibodiesare harmful to vascularized organ allografts.
Preliminary studies with small numbers of patients indicatedthat MICA antibodies detected after transplantation might beassociated with impaired survival of kidney allografts,13,14,15,16,17and an analysis of eluates from kidneys undergoing immunologicrejection has suggested that MICA antibodies may be involvedin the pathogenesis of kidney-allograft rejection.18 Using theresources of the Collaborative Transplant Study, we analyzedserum samples obtained before transplantation from 1910 kidney-transplantrecipients. We tested the serum samples for antibodies againstMICA antigens and correlated the results with the clinical outcome.
Methods
Specimen Collection
Pretransplantation serum samples from 1910 kidney recipientswho underwent transplantation with organs from deceased donorsbetween 1990 and 2004 were provided by 20 centers in 13 countries.The centers included in this analysis provided written assuranceof compliance with local ethical and consent guidelines andof patients' written consent for the use of data for scientificanalysis. The study was approved by the ethics committee ofthe University of Heidelberg.
Laboratory Tests
IgG anti-HLA class I reactivity in the serum samples was testedwith the use of Quickscreen enzyme-linked immunosorbent assay(ELISA) kits and for IgG anti-HLA class II reactivity with theuse of B-Screen ELISA kits (GTI Diagnostics). HLA typing andpanel-reactive HLA antibodies were determined by the tissue-typinglaboratories at the participating centers.
Tests for IgG antibodies against MICA antigens were performedwith the use of soluble MICA antigens produced in insect cellscoupled to polystyrene microbeads (Luminex) in our laboratoryin Dallas. These antigens were based on our previous complementaryDNA constructs of MICA*001, MICA*002, MICA*004, MICA*008, andMICA*009.18 Fragments encoding the signal peptide and the extracellulardomains of these proteins, including a recognition sequencefor enzymatic biotinylation and a six-histidine coding sequencewith a stop codon, were cloned into pEnter-3C vector (Invitrogen)and selected after sequencing. A baculovirus system was usedto produce soluble proteins in High Five insect cells (Invitrogen).These recombinant proteins were affinity purified by nickel-affinityagarose and coupled in duplicate to carboxylated polystyrenemicrospheres and, after biotinylation, to LumAvidin microspheres(Luminex).
For the assay, serum samples or control samples were incubatedwith both sets of beads and reacted with phycoerythrin-conjugatedgoat antihuman IgG (One Lambda). Fluorescence was read witha Luminex 100 flow cytometer (Luminex). A threshold was determinedfor each bead from the mean value for the relative amount ofbinding plus 3 SD in serum samples from 21 healthy persons.According to the relative amount of binding and the thresholdfor each bead, a score of 1 was negative, 2 was doubtful, 4was weakly positive, 6 was positive, and 8 was strongly positive.For the analysis of graft outcome, scores of 1 and 2 were consideredto be negative and scores of 4 to 8 were considered to be positive.Reactions were considered to be positive when the carboxylated-coupledand the avidin-coupled beads with a given antigen were bothpositive.
Statistical Analysis
Allograft function was analyzed 3, 6, and 12 months after transplantation.No patients were excluded for any reason. Twenty-three patients(1.2%) were lost to follow-up within 3 to 6 months after transplantation,and 34 (1.8%) were lost to follow-up between 6 and 12 monthsafter transplantation. Actuarial graft-survival rates were computedaccording to the Kaplan–Meier method19 and expressed asmean (±SE) percentages. Graft survival was compared forpatients with and those without MICA antibodies by means oflog-rank analysis. In addition, multifactorial Cox regressionanalysis was performed20 to consider the effect of potentialconfounders. In this second analysis, we examined the followingcovariables: the year of transplantation; the number of grafts;the ages of the donor and recipient; and the patient's sex andrace, original disease, geographic region (continent), numberof HLA-A plus HLA-B plus HLA-DR mismatches, percentage of panel-reactiveantibodies, HLA class I and class II antibodies, cold-ischemiatime, type of immunosuppression, and number of pretransplantationblood transfusions. Results are given as adjusted hazard ratios.The software packages SPSS (version 14.0) and SAS (version 8.2)were used for statistical analysis.
Results
Table 1 lists the characteristics of the patients. Only threevariables were significantly different among the two groupsof patients. There were slightly more MICA antibody–positiveserum samples from patients who underwent transplantation betweenthe years 2000 and 2004 than among those who underwent transplantationin earlier years. Because serum samples were selected for thisstudy on the basis of available sample volume, aliquots of specimenscollected in earlier years were, in some cases, depleted orreduced to an insufficient quantity for the MICA antibody assay;hence, these earlier sample groups were relatively small. Also,the duration of cold ischemia was slightly longer in the MICAantibody–negative group (Table 1), and a few more patientsin the MICA antibody–positive group received mycophenolicacid as part of their immunosuppressive regimens.
A total of 217 of the 1910 transplant recipients whose serumwas tested for anti-MICA antibodies before transplantation (11.4%)were found to have antibodies against one or more MICA alleles.The presence of MICA antibodies was associated with an increasedrate of kidney-allograft rejection (Figure 1). Patients withanti-MICA antibodies had a 1-year graft-survival rate of 88.3±2.2%as compared with 93.0±0.6% among patients in the MICAantibody–negative group (P=0.01). The difference betweenthe groups was maintained at 5 years after transplantation.When only recipients of first transplants were considered, thegraft-survival rate was 87.8±2.4% among 183 MICA antibody–positivepatients as compared with 93.5±0.6% among the 1473 recipientswho were MICA antibody–negative (P=0.005). In addition,the association of MICA sensitization with reduced graft survivalwas more evident in kidney-transplant recipients with good HLAmatching. Among 326 recipients who received kidneys that werewell matched (0 or 1 HLA-A plus HLA-B plus HLA-DR mismatch),sensitization against MICA was associated with reduced allograftsurvival (83.2±5.8% among those with MICA antibodiesvs. 95.1±1.3% among those without such antibodies; hazardratio for allograft loss, 4.97; P=0.002). In contrast, MICAantibodies were associated with only a small reduction in allograftsurvival, which did not reach statistical significance, forrecipients with less well-matched kidneys (2 to 4 HLA-A plusHLA-B plus HLA-DR mismatches; hazard ratio for allograft loss,1.29; P=0.36) or poorly matched kidneys (5 to 6 HLA-A plus HLA-Bplus HLA-DR mismatches; hazard ratio for allograft loss, 1.63;P=0.50).
Figure 1. Effect of Antibodies against MICA Antigens in Pretransplantation Serum on the Survival of Kidney Transplants from Deceased Donors.
Graft survival is shown for all 1910 patients in the study. The rate of graft survival was lower among the 217 recipients who had antibodies against major-histocompatibility-complex class I–related chain A (MICA) before transplantation (P=0.01).
It appears that the correlation between the presence of anti-MICAantibodies and reduced kidney-allograft survival was not influencedby the simultaneous presence of antibodies against HLA, sincethis was a rare occurrence. Among 1910 patients tested for HLAclass I antibodies, only 37 (1.9%) had both MICA antibodiesand antibodies against HLA class I antigens, and only 35 (1.8%)had both anti-MICA and anti-HLA class II antibodies. Moreover,the presence of antibodies against MICA was highly correlatedwith a poor outcome among recipients who were not sensitizedagainst HLA (Figure 2). Thus, among 1626 patients with 0% panel-reactiveHLA antibodies, there was a higher rate of rejection-relatedallograft loss among 177 patients with antibodies against MICA.The allograft-survival rate in this group was 87.4±2.5%,as compared with 93.4±0.7% among recipients with 0% panel-reactiveHLA antibodies and no antibodies against MICA (P=0.004).
Figure 2. Effect of Antibodies against MICA Antigens in Pretransplantation Serum on Kidney-Graft Survival in Relation to Panel-Reactive HLA Antibodies.
Graft survival is shown for the 1626 patients who were not sensitized against HLA antigens before transplantation (0% panel-reactive HLA antibody value). The rate of graft survival was lower among the 177 recipients with antibodies against major-histocompatibility-complex class I–related chain A (MICA) (P=0.004).
With the use of multivariate analysis, we examined the relationshipbetween the presence of antibodies against MICA among differentsubpopulations of patients (Table 2). There was a significantnegative association between MICA antibodies and allograft survivalamong first kidney-transplant recipients (hazard ratio for allograftloss, 1.86; 95% confidence interval [CI], 1.17 to 2.97; P=0.009),patients who received a transplant with 0 or 1 mismatches forHLA-A, HLA-B, or HLA-DR antigens (hazard ratio for allograftloss, 5.19; 95% CI, 1.94 to 13.88; P=0.001), and patients withno panel-reactive HLA antibodies (hazard ratio for allograftloss, 1.85; 95% CI, 1.23 to 2.78; P=0.003). There were no significanteffects on the outcome for any covariable with antibodies againstMICA.
Table 2. Influence of Antibodies against MICA in Subgroups of Patients.
We attempted to investigate the source of the immunization thatleads to the production of antibodies against MICA in recipientsawaiting kidney transplants. We examined the number of transfusionsreceived by patients with and those without antibodies againstMICA and compared these results with the number of transfusionsreceived by recipients with antibodies against HLA class I andclass II antigens (Table 3). Among 142 patients with antibodiesagainst HLA class I as determined by means of ELISA, 48.6% hadreceived six or more transfusions. In contrast, among 1100 recipientswithout HLA class I antibodies, only 16.9% had received sixor more transfusions (P<0.001). Similarly, the proportionof patients with HLA class II antibodies who had received sixor more transfusions was increased by a factor of more than2 as compared with patients without such antibodies (P<0.001)(Table 3). In contrast, the frequency of transfusions did notdiffer significantly between recipients with and those withoutantibodies against MICA (P=0.15) (Table 3). This result suggeststhat it is likely that antibodies against MICA were not producedin response to immunization by transfusions.
Table 3. Effect of the Number of Pretransplantation Transfusions on Antibodies against HLA Class I, HLA Class II, or MICA.
We did observe, however, that patients sensitized against HLAantigens were somewhat more likely to have antibodies againstMICA as well. Thus, MICA antibodies were found in 37 of 220patients with HLA class I antibodies as determined by meansof ELISA (16.8%), as compared with 180 of 1684 recipients (10.7%)without HLA class I antibodies (P=0.007). Similarly, MICA antibodieswere present in 35 of 204 patients with HLA class II antibodies(17.2%) as determined by means of ELISA, as compared with 182of 1692 (10.8%) of those without HLA class II antibodies (P=0.007).
Discussion
Our study provides evidence that sensitization against MICAantigens before transplantation was associated with decreasedrenal-allograft survival. The graft loss associated with anti-MICAantibodies appears to occur early in the post-transplantationperiod, a typical feature of rejection mediated by preformedantibodies. We have previously reported that some patients awaitingkidney transplantation had antibodies against certain MICA alleles.5,18Among patients in whom an allograft was rejected, the frequencyof antibodies against MICA was higher,16 in keeping with increasedexpression of MICA and MHC class I–related chain B (MICB)in organs undergoing rejection.21,22 Our findings suggest thatpatients with antibodies against MICA before transplantationdid not receive more transfusions than patients without suchantibodies. These findings are in sharp contrast to the knowneffect of transfusions in the production of antibodies againstclass I and class II HLA antigens; this effect was clearly shownin our analysis of serum samples from the same group of patients.Thus, transfusions were unlikely to have caused the appearanceof antibodies against MICA. We speculate that cross-reactivitywith substances from the environment may play a role in primingthe immune system, facilitating MICA antibody production.
The association of MICA antibodies with allograft rejectionwas most clearly observed among recipients who received graftsthat were well matched in terms of HLA-A plus HLA-B plus HLA-DR.When anti-MICA antibodies were detected before transplantation,the loss of grafts within the first 3 months after transplantationwas more common, but differences between the groups were maintainedat the end of the first year after transplantation and beyond.The association of antibodies against MICA antigens and allograftrejection was strong in the group of recipients without panel-reactiveHLA antibodies, suggesting that the immune response to MICAantigens might play a role in rejection in the absence of previoussensitization against HLA. This association with antibodiesagainst MICA was significant in groups of patients commonlyconsidered to be at low risk for allograft rejection: recipientsof first transplants, patients who received grafts from well–HLA-matcheddonors, and recipients not previously sensitized against HLA.In these patients, kidney transplants were lost significantlymore often when antibodies against MICA were present beforethe transplantation. Thus, we hypothesize that the failure ofsome well-matched, low-risk kidney transplants might be explainedby a heretofore undetected immune response against MICA antigens.
Our study has certain limitations. Typing of the donors forMICA antigens could not be performed because donor DNA was notavailable; thus, formal proof of donor specificity could notbe obtained. Also, the mechanism by which antibodies againstMICA antigens develop in recipients before transplantation remainsunknown.
Because of the strong effect of the HLA antigens in transplantrejection, the role of minor histocompatibility antigens inkidney-transplant rejection has not received much attention.However, kidneys from HLA-identical siblings do fail at a ratein keeping with the lower immunogenicity of the minor histocompatibilityloci. Recently one of us reported that transplants from HLA-identicalsiblings fail more frequently among recipients who have higherlevels of panel-reactive antibodies than among those with lowerlevels,23 suggesting that an immune response against antigensother than HLA might play a determining role in kidney-graftfailure. Since the MICA locus is within the MHC, recipientsand donors who are HLA-identical by descent would also invariablybe matched for MICA. Therefore, the observed difference in graftsurvival among recipients of transplants from HLA-identicalsiblings cannot be attributed to MICA. In unrelated transplantswell matched for HLA-A, HLA-B, and HLA-DR, however, mismatchingfor MICA may occur. The association between antibodies againstMICA and allograft rejection was most evident in this well-matchedand low-risk group in our study.
Polymorphisms distinct from those of the HLA system may alsoaffect the outcome of kidney allografts. Antibodies againstendothelial cells were observed among many recipients in whomkidney allografts were rejected.24,25,26 Other polymorphismspossibly associated with kidney-allograft failure are thoseinvolving vimentin,27 platelet-specific antigens,28 genes thatencode various cytokines,29 chemokines and their receptors,30and molecules of the renin–angiotensin system.31
Our earlier studies indicated that antibodies against MICA allelesare produced after transplantation,5 and several subsequentstudies have shown similar findings.13,14,15,16,17 The possibilitythat MICA antigens might be targets during organ-transplantrejection is strengthened by the finding that these antigensare expressed on endothelial cells,12 that MICA, as well asMICB, can be detected in kidneys undergoing rejection,21,22and that anti-MICA antibodies can kill target cells in the presenceof serum complement.13 T cells can recognize and proliferatein response to MICA antigens.32 Other studies have shown thatthe frequency of antibodies against MICA increases after transplantation5,18and that the frequency is higher among recipients who undergokidney-allograft rejection as compared with recipients who donot undergo rejection.17 Additional evidence suggesting thatMICA antigens might be directly involved in kidney-transplantrejection came from a study in which, in collaboration withGrosse-Wilde and coworkers, we analyzed 59 acid eluates fromkidneys determined to have been lost as a result of immunologicrejection.18 Eleven of the eluates contained anti-MICA antibodies,and five eluates contained antibodies against MICA but not againstHLA.
Our current study shows increased rates of allograft failureamong patients with antibodies against MICA before transplantation.Anti-MICA antibodies can be readily detected in serum from patientson the transplant waiting list, and recipients at risk for allograftfailure might thus be identified.
Although we favor the hypothesis that MICA antibodies are causallyinvolved in allograft rejection, we have not formally provedthat the antibodies that correlate with decreased graft survivalare specific for the MICA antigens of the donor. If that turnsout to be the case, it will be important to develop strategiesto reduce or eliminate the effect of MICA antibodies on kidney-graftoutcome.
Supported by the Transplantation Immunology Division, Universityof Texas Southwestern Medical Center, and by the Universityof Heidelberg.
Dr. Stastny reports serving as an invited speaker at histocompatibilityworkshops sponsored by One Lambda; Dr. Opelz, serving as a consultantto Roche and Bristol-Myers Squibb regarding data safety monitoringfor prospective drug trials; and Dr. Süsal, receiving lecturefees from Biotest and Genzyme. No other potential conflict ofinterest relevant to this article was reported.
We thank Daria Perez Alonso for excellent technical assistanceand Barbara A. Moyer for secretarial work with an earlier versionof the manuscript.
Source Information
From the Transplantation Immunology Division, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas (Y.Z., P.S.); and the Department of Transplantation Immunology, University of Heidelberg, Heidelberg, Germany (C.S., B.D., G.O.).
Address reprint requests to Dr. Stastny at the Transplantation Immunology Division, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-8886, or at peter.stastny{at}utsouthwestern.edu.
References
Bahram S, Bresnahan M, Geraghty DE, Spies T. A second lineage of mammalian major histocompatibility complex class I genes. Proc Natl Acad Sci U S A 1994;91:6259-6263. [Free Full Text]
Jinushi M, Takehara T, Kanto T, et al. Critical role of MHC class I-related chain A and B expression on IFN-alpha-stimulated dendritic cells in NK cell activation: impairment in chronic hepatitis C virus infection. J Immunol 2003;170:1249-1256. [Free Full Text]
Menier C, Riteau B, Carosella ED, Rouas-Freiss N. MICA triggering signal for NK cell tumor lysis is counteracted by HLA-G1-mediated inhibitory signal. Int J Cancer 2002;100:63-70. [CrossRef][Web of Science][Medline]
Tieng V, Le Bouguenec C, du Merle L, et al. Binding of Escherichia coli adhesin AfaE to CD55 triggers cell-surface expression of the MHC class I-related molecule MICA. Proc Natl Acad Sci U S A 2002;99:2977-2982. [Free Full Text]
Zwirner NW, Marcos CY, Mirbaha F, Zou Y, Stastny P. Identification of MICA as a new polymorphic alloantigen recognized by antibodies in sera of organ transplant recipients. Hum Immunol 2000;61:917-924. [CrossRef][Web of Science][Medline]
Cardarelli F, Pascual M, Tolkoff-Rubin N, et al. Prevalence and significance of anti-HLA and donor-specific antibodies long-term after renal transplantation. Transpl Int 2005;18:532-540. [CrossRef][Web of Science][Medline]
Kristensen T, Grunnet N, Madsen M, et al. Hyperacute rejection of a kidney allograft may be caused by cytotoxic lymphocytes. Acta Pathol Microbiol Scand [C] 1976;84:304-312. [Web of Science][Medline]
Patel R, Terasaki PI. Significance of the positive crossmatch test in kidney transplantation. N Engl J Med 1969;280:735-739. [Web of Science][Medline]
Jeannet M, Pinn VW, Flax MH, Winn HJ, Russell PS. Humoral antibodies in renal allotransplantation in man. N Engl J Med 1970;282:111-117. [Web of Science][Medline]
Trpkov K, Campbell P, Pazderka F, Cockfield S, Solez K, Halloran PF. Pathologic features of acute renal allograft rejection associated with donor-specific antibody: analysis using the Banff grading schema. Transplantation 1996;61:1586-1592. [CrossRef][Web of Science][Medline]
Lee PC, Terasaki PI, Takemoto SK, et al. All chronic rejection failures of kidney transplants were preceded by the development of HLA antibodies. Transplantation 2002;74:1192-1194. [CrossRef][Web of Science][Medline]
Zwirner NW, Dole K, Stastny P. Differential surface expression of MICA by endothelial cells, fibroblasts, keratinocytes, and monocytes. Hum Immunol 1999;60:323-330. [CrossRef][Web of Science][Medline]
Zou Y, Mirbaha F, Lazaro A, Zhang Y, Lavingia B, Stastny P. MICA is a target for complement-dependent cytotoxicity with mouse monoclonal antibodies and human alloantibodies. Hum Immunol 2002;63:30-39. [CrossRef][Web of Science][Medline]
Sumitran-Holgersson S, Wilczek HE, Holgersson J, Soderström K. Identification of the nonclassical HLA molecules, MICA, as targets for humoral immunity associated with irreversible rejection of kidney allografts. Transplantation 2002;74:268-277. [CrossRef][Web of Science][Medline]
Mizutani K, Terasaki P, Bignon JD, et al. Association of kidney transplant failure and antibodies against MICA. Hum Immunol 2006;67:683-691. [CrossRef][Web of Science][Medline]
Mizutani K, Terasaki P, Rosen A, et al. Serial ten-year follow-up of HLA and MICA antibody production prior to kidney graft failure. Am J Transplant 2005;5:2265-2272. [CrossRef][Web of Science][Medline]
Mizutani K, Terasaki PI, Shih RN, Pei R, Ozawa M, Lee J. Frequency of MIC antibody in rejected renal transplant patients without HLA antibody. Hum Immunol 2006;67:223-229. [CrossRef][Web of Science][Medline]
Zou Y, Heinemann FM, Grosse-Wilde H, et al. Detection of anti-MICA antibodies in patients awaiting kidney transplantation, during the post-transplant course, and in eluates from rejected kidney allografts by Luminex flow cytometry. Hum Immunol 2006;67:230-237. [CrossRef][Web of Science][Medline]
Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958;53:457-481. [CrossRef][Web of Science]
Cox DR. Regression models and life-tables. J R Stat Soc [B] 1972;34:187-220.
Hankey KG, Drachenberg CB, Papadimitriou JC, et al. MIC expression in renal and pancreatic allografts. Transplantation 2002;73:304-306. [CrossRef][Web of Science][Medline]
Quiroga I, Salio M, Koo DD, et al. Expression of MHC class I-related chain B (MICB) molecules on renal transplant biopsies. Transplantation 2006;81:1196-1203. [CrossRef][Web of Science][Medline]
Opelz G. Non-HLA transplantation immunity revealed by lymphocytotoxic antibodies. Lancet 2005;365:1570-1576. [CrossRef][Web of Science][Medline]
Moraes JR, Stastny P. Allo-antibodies to endothelial cell antigens. In: Kissmeyer-Nielsen F, ed. VI International Histocompatibility Workshop and Conference; 1975 June 29 to July 5; Arhus, Denmark. Copenhagen: Munksgaard, 1975:391-7.
A new antigen system expressed in human endothelial cells. J Clin Invest 1977;60:449-454. [Web of Science][Medline]
Vermehren D, Sumitran-Holgersson S. Isolation of precursor endothelial cells from peripheral blood for donor-specific crossmatching before organ transplantation. Transplantation 2002;74:1479-1486. [CrossRef][Web of Science][Medline]
Carter V, Shenton BK, Jaques B, et al. Vimentin antibodies: a non-HLA antibody as a potential risk factor in renal transplantation. Transplant Proc 2005;37:654-657. [CrossRef][Web of Science][Medline]
Kekomäki S, Kyllönen L, Salmela K, Koskimies S, Kekomäki R. Platelet-specific alloantigens in cadaveric renal transplantation: a prospective study: effect of HPA-5b mismatch in acute vascular rejection of renal allografts. Tissue Antigens 2001;57:154-157. [CrossRef][Web of Science][Medline]
Tinckam K, Rush D, Hutchinson I, et al. The relative importance of cytokine gene polymorphisms in the development of early and late acute rejection and six-month renal allograft pathology. Transplantation 2005;79:836-841. [CrossRef][Web of Science][Medline]
Abdi R, Tran TB, Sahagun-Ruiz A, et al. Chemokine receptor polymorphism and risk of acute rejection in human renal transplantation. J Am Soc Nephrol 2002;13:754-758. [Free Full Text]
Dragun D, Müller DN, Bräsen JH, et al. Angiotensin II type 1-receptor activating antibodies in renal-allograft rejection. N Engl J Med 2005;352:558-569. [Free Full Text]
Zhang Y, Stastny P. MICA antigens stimulate T cell proliferation and cell-mediated cytotoxicity. Hum Immunol 2006;67:215-222. [CrossRef][Web of Science][Medline]
Grafft, C. A., Cornell, L. D., Gloor, J. M., Cosio, F. G., Gandhi, M. J., Dean, P. G., Stegall, M. D., Amer, H.
(2009). Antibody-mediated rejection following transplantation from an HLA-identical sibling. Nephrol Dial Transplant
0: gfp526v1-gfp526
[Abstract][Full Text]
Parmar, S., del Lima, M., Zou, Y., Patah, P. A., Liu, P., Cano, P., Rondon, G., Pesoa, S., de Padua Silva, L., Qazilbash, M. H., Hosing, C., Popat, U., Kebriaei, P., Shpall, E. J., Giralt, S., Champlin, R. E., Stastny, P., Fernandez-Vina, M.
(2009). Donor-recipient mismatches in MHC class I chain-related gene A in unrelated donor transplantation lead to increased incidence of acute graft-versus-host disease. Blood
114: 2884-2887
[Abstract][Full Text]
Li, L., Wadia, P., Chen, R., Kambham, N., Naesens, M., Sigdel, T. K., Miklos, D. B., Sarwal, M. M., Butte, A. J.
(2009). Identifying compartment-specific non-HLA targets after renal transplantation by integrating transcriptome and "antibodyome" measures. Proc. Natl. Acad. Sci. USA
106: 4148-4153
[Abstract][Full Text]
Sun, Q., Liu, Z., Chen, J., Chen, H., Wen, J., Cheng, D., Li, L.
(2008). Circulating Anti-endothelial Cell Antibodies Are Associated with Poor Outcome in Renal Allograft Recipients with Acute Rejection. CJASN
3: 1479-1486
[Abstract][Full Text]
Magee, C., Clarkson, M., Rennke, H.
(2008). A Case of Desensitization, Transplantation, and Allograft Dysfunction. CJASN
3: 1573-1581
[Full Text]
Gebel, H. M., Bray, R. A.
(2008). Approaches for transplanting the sensitized patient: biology versus pharmacology. Nephrol Dial Transplant
23: 2454-2457
[Full Text]
Jevnikar, A. M., Mannon, R. B.
(2008). Late Kidney Allograft Loss: What We Know about It, and What We Can Do about It. CJASN
3: S56-S67
[Abstract][Full Text]
Kamoun, M., Grossman, R. A., Baid-Agrawal, S., Frei, U. A., Dragun, D., Scornik, J., Meier-Kriesche, H.-U., Stastny, P., Zou, Y., Opelz, G.
(2008). Kidney-Transplant Rejection and Anti-MICA Antibodies. NEJM
358: 195-196
[Full Text]
Flegel, W. A.
(2007). Will MICA Glitter for Recipients of Kidney Transplants?. NEJM
357: 1337-1339
[Full Text]
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