Chlamydia ; immunology ; pathogenicity ; physiology ; Histocompatibility Antigens Class I ; biosynthesis ; immunology ; Humans ; Immune Tolerance ; immunology ; Muramidase ; immunology

OBJECTIVETo review the role of polymorphism of major histocompatibility complex class I-related chain A (MICA) gene and antibodies against MICA antigens in transplant immunology.

DATA SOURCESThe data used in this review were mainly from our own results and from the relevant English language literatures published from 1999 to 2010. Some data presented in this review are in press.

STUDY SELECTIONArticles regarding MICA gene discovery and pioneering finding of antibodies against MICA antigen and allograft rejection were selected. This review chronicles the development of our understanding of the role that MICA antigens and antibodies may play in organ transplantation.

RESULTSPolymorphic glycoprotein MICA antigens were detected on freshly isolated human umbilical cord endothelial cells, but not on peripheral lymphocytes. Antibodies were found and typing of recipients and donors by sequencing the MICA alleles has established that de novo antibodies produced in kidney transplant recipients are directed at mismatched MICA epitopes and are associated with acute rejection and chronic transplant failure. The specificity of antibodies against the epitopes of MICA antigens were well characterized by donor MICA typing, single antigen array testing with antibody absorption and elution. Acute graft-versus-host disease was observed in stem-cell recipients who were mismatched for MICA.

CONCLUSIONSImmunization against mismatched MICA epitopes encountered in donor organs after transplantation may result in antibodies against MICA alleles. Testing for MICA donor-specific antibodies (DSA) which are associated with early failure of kidney transplants may be helpful for identifying some of the targets of antibodies against antigens other than the human leukocyte antigen (HLA) and for improving transplantation outcome.

Antibodies ; immunology ; Graft Rejection ; immunology ; Histocompatibility Antigens Class I ; immunology ; Humans ; Organ Transplantation

BACKGROUND: For the detection of HLA antibodies, solid-phase tests using purified HLA antigens are increasingly used. In this study, we analyzed the panel reactive antibody (PRA) test results using ELISA and Luminex methods, and the results were compared with those of crossmatch test. METHODS: A total of 111 sera including 90 sera from kidney transplanted patients were tested. ELISA-PRA was performed using Lambda Antigen Tray Class I and II Mixed kits (One Lambda Inc., USA) and additional test was performed to identify HLA specificities. Luminex-PRA tests were performed using LABScreen Mixed kits (One Lambda Inc., USA) and LIFECODES LifeScreen Deluxe kits (Tepnel Co., USA). RESULTS: The positive rates of PRA were higher in Tepnel (P=0.006) and One Lambda Luminex (P<0.001) methods than ELISA, without significant difference between two Luminex methods (P=0.087). The overall concordance rate among the three PRA tests was 62.2% (69/111). The positive and negative predictive values of PRA tests for the flow cytometric crossmatch were 33.3-45.7% and 85.7-89.5%, respectively. Of the two Luminex methods, One Lambda showed higher positive rate than Tepnel for the detection of class I antibodies. The sensitivity of pretransplant PRA for the detection of posttransplant acute rejection episodes was higher in Luminex (P=0.007 for Tepnel, P=0.003 for One lambda) than ELISA method. CONCLUSIONS: Different methods used to detect HLA antibodies showed discrepant results. As the Luminex method was more sensitive than ELISA for the detection of HLA antibodies, it can be used as a routine test in the transplantation laboratory.
Enzyme-Linked Immunosorbent Assay/*methods ; Flow Cytometry ; Histocompatibility Antigens Class I/*immunology ; Histocompatibility Antigens Class II/*immunology ; Humans ; Isoantibodies/*blood ; Kidney Transplantation/immunology ; Reagent Kits, Diagnostic ; Sensitivity and Specificity

The study was aimed to investigate the expression of HLA class I molecules and MHC class I chain-related molecules A/B (MICA/MICB) in K562 and adriamycin (ADM)-resistant K562 cell lines (K562/AO2) and their effect on cytotoxicity of NK cells. Expression of HLA class I molecules and MICA/MICB on the surface of K562 and K562/AO2 cell lines were analyzed by flow cytometry. Cytotoxicity of NK cells (isolated from 3 healthy persons) against K562 and K562/AO2 cells were detected by LDH releasing assay at different effect-to-target cell ratios (E:T). In blocking experiments, anti-MHC class I monoclonal antibody (McAb) (W6/32, a pan anti-HLA class I antibody) and anti-MHC class I chain-related molecules McAb (BAMO-1, specifically against MICA and MICB) were added to the target cells at E:T of 10:1. The results showed that the expression of MHC class I chain-related molecules on K562 was higher than that on K562/AO2 (P=0.000), and HLA class I molecules were not detectable on both cells. Cytotoxicities of NK cells against K562 and K562/AO2 cells were (29.32 +/- 0.12)%, (45.33 +/- 0.78)%, (58.37 +/- 0.87)%, (72.37 +/- 0.96)% and (12.47 +/- 0.91)%, (24.36 +/- 1.11)%, (33.29 +/- 1.03)%, (53.87 +/- 1.27)% at E:T ratios of 5:1, 10:1, 20:1 and 30:1 respectively (P=0.000), the cytotoxicity of NK cells on K562 cells was significantly higher than that on K562/A02 cells at different E:T ratios. Blocking experiments confirmed that at E:T of 10:1 killing of NK cells against K562 and K562/AO2 cells was efficiently inhibited by BAMO-1, whereas W6/32 had no effect on K562 and K562/AO2 cells. It is concluded that the expression of MHC class I chain-related molecules on K562 and K562/AO2 cells is correlated with NK cell-mediated lysis. NK cells display higher cytotoxicity against parental K562 cells than multi-drug resistant K562/AO2 cells. Down-regulation of MICA/B in multi-drug resistant tumor cell lines leads to reduction of susceptibility to NK lysis.
Cytotoxicity, Immunologic ; immunology ; Doxorubicin ; pharmacology ; Drug Resistance, Neoplasm ; immunology ; Genes, MHC Class I ; genetics ; Histocompatibility Antigens Class I ; immunology ; Humans ; K562 Cells ; Killer Cells, Natural ; immunology

BACKGROUNDHumoral immunity is an important factor for long-term survival of renal allograft. Here we performed a four-year follow-up to explore the clinical significance of monitoring anti-human leukocyte antigens (HLA) and anti-major histocompatibility complex class I-related chain A (MICA) antibody expression after kidney transplantation.

METHODSWe obtained serial serum samples from 84 kidney transplant patients over a four-year period. All patients were followed up at least 6 months after transplantation and had at least two follow-up points. Anti-HLA and anti-MICA antibody titres and serum creatinine (SCr) levels were evaluated at each follow-up. Patients were divided into 4 groups: HLA(+) MICA(-), HLA(-)MICA(+), HLA(+)MICA(+) and HLA(-)MICA(-). The impact of post-transplant antibody level on kidney allograft function was evaluated.

RESULTSAntibodies were detected in 38.1% (32/84) of the renal allograft recipients. HLA, MICA and HLA+MICA expression was observed in 18.89%, 14.44% and 5.93% of the recipients respectively. The most frequent anti-HLA and anti-MICA specific antibodies identified were A11, A24, A29, A32, A33, A80; B7, B13, B37; DR17, DR12, DR18, DR52, DR53, DR1, DR4, DR9, DR51; DQ7, DQ4, DQ8, DQ2, DQ9, DQ5, DQ6 and MICA02, MICA18, MICA19, MICA07, MICA27. As the time after transplantation elapsed, more recipients developed de novo antibody expression. Total 11.91% (10/84) of the recipients had de novo antibody expression during the follow up. The average level of SCr and the percentage of recipients with abnormal allograft function were significantly higher in recipients with anti-HLA and/or anti-MICA antibody expression than those without. The appearance of anti-HLA and anti-MICA antibody expression always preceded the increase in SCr value.

CONCLUSIONSAnti-HLA and anti-MICA antibody expression has predictive value for early and late allograft dysfunction. The presence of donor specific antibody is detrimental to graft function and graft survival.

Female ; Follow-Up Studies ; Graft Survival ; HLA Antigens ; immunology ; Histocompatibility Antigens Class I ; immunology ; Humans ; Isoantibodies ; analysis ; Kidney Transplantation ; Male ; Minor Histocompatibility Antigens

Behcet's disease is a chronic multi-systemic disease of unknown origin that includes mucocutaneous, ocular, cardiac, vascular, renal, gastrointestinal, neurologic and cutaneous involvement. The disease is spread throughout the world, but it is most prevalent in the eastern Mediterranean region-along the Silk Road-, and in Japan, China, and Korea. Recently, we treated a Mongolian patient who had complete-type Behcet's disease. As far as we know, this case is the first report of a Mongolian with Behcet's disease in the English literature. HLA typing in this patient revealed A2, A24; B51, B35; Cw4, Cw7; DR9, DR11. Study of the MICA genetype showed *5, *6 positive. Our data provided adequate evidence, from an epidemiological aspect, to support the belief that Behcet's disease is most prevalent along the old Silk Road.
Adult ; Alleles ; Behcet Syndrome/*genetics/immunology ; Genotype ; HLA-B Antigens/*genetics ; Histocompatibility Antigens Class I/*genetics ; Human ; Male

BACKGROUND: Panel reactive antibody (PRA) is to screen and identify HLA antibody. Majority of antibody specificities in high-PRA are directed against cross reactive group (CREG). Thus, this study was to know the advantage of identifying CREG specificity and whether antibody specificities are changed according to CREG classification. METHODS: HLA class I antibodies were identified from 159 sera from 108 patients in Asan Medical Center, who had shown more than 5% PRA by anti-human globulin (AHG)-complement-dependent cytotoxicity (CDC). Tail analysis-based computer program was developed to identify specificities, applying both Rodey (R-ABC) and Takemoto (T-ABC) classification. The results were also compared with those obtained when without CREG application (ABC). RESULTS: Among 151 cases in which HLA specificities was identified, the frequency of CREG specificity was 22.5% in R-ABC and 27.2% in T-ABC. Eleven cases showed CREG specificities only in one classification. However, the individual antigen specificities in one hand were all included in the CREG identified in the other hand. CREG specificities in samples with PRA >50% (60%) were more frequently identified than those in samples with PRA < or =50% (9%) (in R-ABC, P<0.0001). Without applying CREG to interpretation, specificity was not identified in 9 cases. CONCLUSIONS: Application of CREG enhanced the rate of antibody identification. Antibody specificities of those cases where CREG specificities were different between Rodey and Takemoto classifications were almost the same when compared at the individual antigen level. Therefore, it was thought that it makes no difference to use any one of these two classifications in interpreting PRA.
Alleles ; Antibodies/blood ; *Antibody Specificity ; Cross Reactions ; HLA Antigens/genetics/*immunology ; Histocompatibility Antigens Class I/immunology ; Histocompatibility Testing ; Humans ; Kidney Transplantation ; Reproducibility of Results ; Retrospective Studies

The objective of this study was to investigate the method and effect of blocking the specific reaction between lymphocyte HLA-I antigen and its antibody. The lymphocytes were disposed with 12 mmol/L methoxypolyethelene glycol benzotriazol carbonate (mPEG-BTC) in concentration gradient in PBS (pH 7.4) at 22 degrees C. The effect of the modified lymphocytes was detected by microlymphocytotoxicity assay. The results showed that lymphocytes modified by mPEG-BTC did not react with related HLA-I antibodies in microcytotoxicity test. It is suggested that the specific reaction between HLA-I antigen of lymphocyte and HLA-I antibodies can be completely camouflaged by mPEG-BTC in PBS (pH 7.4) under 22 degrees C room temperature.
Antigen-Antibody Reactions ; Cytotoxicity, Immunologic ; Histocompatibility Antigens Class I ; immunology ; Humans ; Lymphocytes ; immunology ; Polyethylene Glycols ; pharmacology ; Triazoles ; pharmacology

OBJECTIVETo investigate the risk factors for sensitization of anti-MICA antibodies and their impact on the outcomes of renal transplantation.

METHODSLuminex flow cytometry were used to identify 10 MICA antibodies and evaluate the antibody specificity in 98 uremic patients positive or negative for anti-MICA antibodies undergoing kidney transplantation. The factors contributing to MICA sensitization were analyzed, and the incidence of acute rejection and graft function recovery time were compared between the positive and negative cases for anti-MICA antibodies.

RESULTSOf the 98 uremic patients, 16 (16.3%) were positive for anti-MICA antibodies. The positive and negative cases showed significant differences in the history of blood transfusion, pregnancy, transplantation, and PRA status (P<0.05). In the 38 renal transplant recipients, 6 experienced acute graft rejection, which was reversed by methylprednisolone pulse therapy; of the 10 recipients positive for anti-MICA antibodies, 4 showed acute graft rejection as compared to 2 out of the 28 recipients negative for anti-MICA antibodies (P=0.031). The cases positive for anti-MICA antibodies showed a significantly longer graft function recovery time than the negative cases (14.6∓4.7 vs 8.2∓4.5 days, P=0.001).

CONCLUSIONSBlood transfusion, pregnancy, and transplantation all contribute to the production of anti-MICA antibodies. Patients positive for anti-MICA antibodies may require strict HLA matching and more potent immunosuppressive drugs to prevent renal graft rejection and improve graft survival.

Adult ; Antibodies, Anti-Idiotypic ; immunology ; Antibody Specificity ; Blood Transfusion ; Female ; Genes, MHC Class I ; immunology ; Graft Survival ; Histocompatibility Antigens Class I ; immunology ; Histocompatibility Testing ; Humans ; Kidney Transplantation ; immunology ; Male ; Middle Aged ; Pregnancy ; Risk Factors ; Uremia ; immunology ; surgery

Transfusion-related acute lung injury (TRALI) is a serious adverse transfusion reaction that is presented as acute hypoxemia and non-cardiogenic pulmonary edema, which develops during or within 6 hr of transfusion. Major pathogenesis of TRALI is known to be related with anti-HLA class I, anti-HLA class II, or anti-HNA in donor's plasma. However, anti-HLA or anti-HNA in recipient against transfused donor's leukocyte antigens also cause TRALI in minor pathogenesis and which comprises about 10% of TRALI. Published reports of TRALI are relatively rare in Korea. In our cases, both patients presented with dyspnea and hypoxemia during transfusion of packed red blood cells and showed findings of bilateral pulmonary infiltrations at chest radiography. Findings of patients' anti-HLA antibodies and recipients' HLA concordance indicate that minor pathogenesis may be not as infrequent as we'd expected before. In addition, second case showed that anti-HLA class II antibodies could be responsible for immunopathogenic mechanisms, alone.
Acute Lung Injury/*diagnosis/*immunology/radiography ; Aged ; Anoxia/diagnosis ; Antigen-Antibody Reactions ; Blood Transfusion/*adverse effects ; Dyspnea/diagnosis ; Female ; HLA Antigens/*immunology ; Histocompatibility Antigens Class I/immunology ; Histocompatibility Antigens Class II/immunology ; Humans ; Isoantibodies/*blood ; Male ; Middle Aged