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ABSTRACT: PURPOSE: Living-donor lobar lung transplantation (LDLLT) has been successfully performed in Japan. In LDLLT, the recipient usually receives one lower lobe from each of two donors; however, finding two ABO-matched donors is often difficult. Solid organ transplants from donors with minor ABO-mismatches can be complicated by hemolysis. We investigated the incidence of de novo anti-ABO antibody production and hemolysis in patients receiving LDLLT across minor ABO-mismatches. METHODS: We evaluated 23 patients who underwent LDLLT between June 2008 and December 2011, including 11 patients who underwent minor ABO-mismatched transplantation. We measured the anti-A/B antibody serum titers, hemoglobin concentrations and indirect bilirubin levels. RESULTS: None of the patients showed any clinical signs of hemolytic anemia (mean follow-up period; 16 months). Two of the 11 patients (18 %) receiving minor ABO-mismatched LDLLTs showed a small amount of de novo anti-B antibodies for a transient period. These patients showed gradual progression of anemia, and weak de novo anti-A/B antibodies were detected with column agglutination technology. The patients received only 2 U of washed type O red blood cells; thereafter, the hemolytic anemia did not develop further in either case. CONCLUSION: LDLLT across minor ABO-mismatches results in the transient appearance of weak de novo anti-A/B antibodies with a low incidence; thus, this procedure can be a safe treatment.
Surgery Today 11/2012; · 1.22 Impact Factor
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ABSTRACT: The role of donor-specific anti-HLA antibodies (DSA) that develop late after living-donor liver transplantation is unknown. Seventy-nine pediatric recipients who have good graft function with available protocol liver biopsy more than 5 years post-transplant (median 11 years; range, 5-20) were reviewed. DSA determined by the Luminex Single Antigen bead assay at the last biopsy and C4d immunostaining were assessed at the last and previous biopsies. Of the 67 patients in whom the donor specificity of antibodies could be identified, DSA was detected in 32 patients (48%), usually against HLA class II (30 cases), but rarely against class I (2 cases). These patients had a higher frequency of bridging fibrosis or cirrhosis (28/32, 88%) than DSA-negative patients (6/36, 17%; p<0.001). Fibrosis was likely to be centrilobular-based. DSA-positive patients showed a higher frequency of diffuse/focal endothelial C4d staining (p<0.001) and of mild/indeterminate acute rejection than DSA-negative patients (15/32 47% vs. 5/35 14%, p=0.004). Four DSA-negative patients were off immunosuppression compared with none in the DSA-positive group (p=0.048). In conclusion, the high prevalence of graft fibrosis and anti-class II DSA in late protocol biopsies suggests that humoral alloreactivity may contribute to the process of unexplained graft fibrosis late after liver transplantation. Liver Transpl, 2012. © 2012 AASLD.
Liver Transplantation 08/2012; · 3.39 Impact Factor
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Fengshi Chen,
Naomi Chibana,
Akihiro Kanematsu,
Shunji Takakura, Kimiko Yurugi,
Rie Hishida,
Atushi Fukatsu,
Takeshi Kubo,
Tsuyoshi Shoji,
Takuji Fujinaga,
Toru Bando,
Hiroshi Date
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ABSTRACT: We report a case of antibody-mediated rejection (AMR) of a unilateral donor lung in the presence of newly formed donor-specific antibodies, 10 months after living-donor lobar lung transplantation (LDLLT). Of note is that the AMR occurred in the unilateral lung. Furthermore, the lung graft was from her husband and HLA analysis on the recipient's daughter revealed the same donor-specific HLA antigens, which strongly suggested pre-sensitization before lung transplantation. Fortunately, we could perform direct crossmatch even 1 year after lung transplantation because of the living donors.
Surgery Today 02/2012; 42(8):808-11. · 1.22 Impact Factor
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Tomohide Hori,
Toshimi Kaido,
Fumitaka Oike,
Yasuhiro Ogura,
Kohei Ogawa,
Yukihide Yonekawa,
Koichiro Hata,
Yoshiya Kawaguchi,
Mikiko Ueda,
Akira Mori, [......],
Hiroto Egawa,
Atsushi Yoshizawa,
Takuma Kato,
Kanako Saito,
Linan Wang,
Mie Torii,
Feng Chen,
Ann-Marie T Baine,
Lindsay B Gardner,
Shinji Uemoto
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ABSTRACT: To investigate thrombotic microangiopathy (TMA) in liver transplantion, because TMA is an infrequent but life-threatening complication in the transplantation field.
A total of 206 patients who underwent living-donor liver transplantation (LDLT) were evaluated, and the TMA-like disorder (TMALD) occurred in seven recipients.
These TMALD recipients showed poor outcomes in comparison with other 199 recipients. Although two TMALD recipients successfully recovered, the other five recipients finally died despite intensive treatments including repeated plasma exchange (PE) and re-transplantation. Histopathological analysis of liver biopsies after LDLT revealed obvious differences according to the outcomes. Qualitative analysis of antibodies against a disintegrin-like domain and metalloproteinase with thrombospondin type 1 motifs (ADAMTS-13) were negative in all patients. The fragmentation of red cells, the microhemorrhagic macules and the platelet counts were early markers for the suspicion of TMALD after LDLT. Although the absolute values of von Willebrand factor (vWF) and ADAMTS-13 did not necessarily reflect TMALD, the vWF/ADAMTS-13 ratio had a clear diagnostic value in all cases. The establishment of adequate treatments for TMALD, such as PE for ADAMTS-13 replenishment or treatments against inhibitory antibodies, must be decided according to each case.
The optimal induction of adequate therapies based on early recognition of TMALD by the reliable markers may confer a large advantage for TMALD after LDLT.
World Journal of Gastroenterology 04/2011; 17(14):1848-57. · 2.47 Impact Factor
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ABSTRACT: The amount of antibody in blood is an important measure of health status for making critical decisions in clinical practice. Here, we demonstrated a single-step, label-free, molecular diagnostic method based on localized surface plasmon resonance (LSPR) using standard 96-well microtiter plates. We improved the LSPR biosensor so that it can measure antibodies to blood group antigens in human serum with a single-step operation. First, we employed the ampholytic polymeric surface modification technique to present an efficient molecular scaffold on the sensor surface. Second, we selected the combination of an appropriate reference molecule against the antigen and a blocking agent to significantly reduce the variability of signal due to nonspecific responses of the unknown in the sample. Finally, we overcame the analytical difficulty arising from serum and achieved a single-step "wash-free" measurement of the amount of target antibody in human serum. FROM THE CLINICAL EDITOR: In this paper, a novel, single-step, label-free, molecular diagnostic method is discussed for antibody detection based on localized surface plasmon resonance using standard 96-well microtiter plates.
Nanomedicine: nanotechnology, biology, and medicine 02/2011; 7(6):889-95. · 5.44 Impact Factor
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ABSTRACT: ABO-incompatible living-donor lobar lung transplantation was performed in a 10-year-old boy with bronchiolitis obliterans (BO) after bone marrow transplantation (BMT) for recurrent acute myeloid leukemia (AML). His blood type had changed from AB to O since he underwent BMT and he had no anti-A/B antibody, and received type B and AB donor lobar lungs. To our knowledge, this case represents the first successful living-donor lobar lung transplantation from ABO-incompatible donors.
The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation 12/2010; 30(4):479-80. · 3.54 Impact Factor
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Tomohide Hori,
Shinji Uemoto,
Yasutsugu Takada,
Fumitaka Oike,
Yasuhiro Ogura,
Kohei Ogawa,
Aya Miyagawa-Hayashino, Kimiko Yurugi,
Justin H Nguyen,
Yukinobu Hori,
Feng Chen,
Hiroto Egawa
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ABSTRACT: There is still no consensus on the importance of lymphocyte cross-matching (LCM) in the field of living-donor liver transplantation (LDLT).
LCM examinations are routinely performed before LDLT, and the results of complement-dependent cytotoxicity were used in this study. A total of 1157 LDLT cases were evaluated. The recipients were divided into four groups based on the LCM and ABO compatibilities: (1) negative LCM and identical/compatible ABO; (2) negative LCM and incompatible ABO; (3) positive LCM and identical/compatible ABO; and (4) positive LCM and incompatible ABO. The diagnosis of antibody-mediated rejection (AMR) was made based on the clinical course, immunological assays and histopathological findings. C4d immunostaining was added if AMR was suspected.
The LCM-positive LDLT recipients showed significantly poorer outcomes than the LCM-negative recipients. Among the LCM-positive recipients, 44.1% of recipients eventually died and 85.2% of recipients revealed positive C4d findings. The survival rate of LCM-positive and ABO-incompatible group was 0.50. The survival days were compared with the LCM-negative and ABO-identical/compatible group, and the LCM-positive and ABO-identical/compatible group clearly showed early death after LDLT, although the ABO-incompatible groups did not show significant. The factors of age, disease, pre-transplant scores, LCM, ABO compatibility and graft-recipient weight ratio showed statistical significance in multivariate analysis for important factors of LDLT outcomes. However, the LCM and ABO compatibilities had no synergetic effects on the LDLT survival.
HLA antigens are more widely expressed than ABO antigens, and advanced immunological strategies must be established for LCM-positive LDLT as well as for ABO-incompatible LDLT.
Surgery 06/2010; 147(6):840-4. · 3.10 Impact Factor
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Hiroto Egawa,
Katsuyuki Ohmori,
Hironori Haga,
Hiroaki Tsuji, Kimiko Yurugi,
Aya Miyagawa-Hayashino,
Fumitaka Oike,
Akinari Fukuda,
Jun Yoshizawa,
Yasutsugu Takada,
Koichi Tanaka,
Taira Maekawa,
Kazue Ozawa,
Shinji Uemoto
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ABSTRACT: Although the effectiveness of rituximab has been reported in ABO blood group (ABO)-incompatible (ABO-I) organ transplantation, the protocol is not yet established. We studied the impact of the timing of rituximab prophylaxis and the humoral immune response of patients undergoing ABO-I living donor liver transplantation (LDLT), focusing on clinicopathological findings and the B-cell subset. From July 2003 to December 2005, 30 adult patients were treated with hepatic artery infusion (HAI) protocol without splenectomy for ABO-I LDLT. A total of 17 patients were treated only with HAI (no prophylaxis), and the other 13 were treated with rituximab prophylaxis at various times prior to transplantation. For B-cell study of the spleen, another 4 patients undergoing ABO-I LDLT both with HAI after prophylaxis and eventual splenectomy, and 3 patients with ABO-compatible LDLT with splenectomy were enrolled. The mortality of the 30 patients with HAI, without splenectomy, and with/without rituximab prophylaxis was 33% and the main cause of death was sepsis. Peripheral blood B cells were completely depleted, anti-donor blood-type antibody titer was lower, and clinical and pathological antibody-mediated rejection was not observed in patients with prophylaxis earlier than 7 days before transplantation (early prophylaxis). Early rituximab prophylaxis significantly depleted B cells and memory B cells in the spleen but not in lymph nodes. On the other hand, B cells and memory B cells increased and memory B cells became dominant during antibody-mediated rejection. In conclusion, early prophylaxis with rituximab depletes B cells, including memory B cells, in the spleen and is associated with a trend toward lower humoral rejection rates and lower peak immunoglobulin (Ig)G titers in ABO-I LDLT patients.
Liver Transplantation 04/2007; 13(4):579-88. · 3.39 Impact Factor
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ABSTRACT: We retrospectively determined the correlation of results of lymphocyte crossmatch tests by direct complement-dependent cytotoxicity, to the outcomes of 585 consecutive ABO-identical and human leukocyte antigen (HLA)-mismatched living donor liver transplants (LDLTs) (male:female=276:309; median age, 18 years). Crossmatch test results were positive in 14 recipients (2.4%). Patient survival at eight years in the crossmatch-positive group was significantly lower than in the crossmatch-negative group (positive group, 56.3%; negative group, 77.6%; P=0.014). The survival at five years of the crossmatch-positive group was significantly lower than the negative group in both older recipients (>or=18 years of age: positive group, 41.7%; negative group, 76.4%; P=0.0065), and female recipients (positive group, 37.5%; negative group, 81.9%; P=3.3x10). We conclude that antidonor antibodies have adverse effects on the clinical outcome of LDLTs, and that being female and/or older aged (>or=18 years of age) are risk factors for LDLT.
Transplantation 02/2007; 83(4):506-9. · 4.00 Impact Factor
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ABSTRACT: The measurement of anti-blood group A/B (anti-A/B) IgG antibody levels is important for ABO unmatched-organ recipients because the effective removal of the antibodies improves their prognosis. Living-donor liver transplantation (LDLT) into ABO-unmatched patients tends to have a very poor outcome due to major complications such as intrahepatic bile duct complications and hepatic necrosis. Sustained bile duct complications are associated with high preoperative IgM type anti-A/B Ab titers, while patients with high preoperative IgG type anti-A/B Ab titers frequently develop sustained hepatic necrosis. There are several existing methods by which anti-A/B Ab levels can be measured, including the standard tube (TT) method, an enzyme-linked immunosorbent assay, and a flow cytometry method. Anti-A/B IgG Ab is difficult to identify by the TT method, which is the most popular method and is based on the detection of hemagglutination, because the major isotype that facilitates red cell agglutination is the pentameric IgM molecule. Therefore, we have developed a method based on surface plasmon resonance (SPR) that detects the presence of the antigen-antibody complex without any labeling. This method allows us to rapidly quantitate anti-A/B IgG Ab levels.
Rinsho byori. The Japanese journal of clinical pathology 12/2005; 53(11):1011-8.
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ABSTRACT: Living-donor liver transplantation (LDLT) has been an important option in the treatment of patients with end-stage liver disease. Massive intraoperative blood loss can occur during LDLT, necessitating blood transfusion. The purpose of this study was to present blood loss data from the recipients of LDLT, to assess the effect of massive intraoperative blood loss on prognosis, and to assess the reliability of preoperative information in predicting intraoperative blood transfusion requirements in LDLT.
A total of 635 patients who underwent LDLTs between January 1995 and March 2002 at a university hospital were retro- spectively investigated. The volume of blood loss, prognosis, and preoperative variables were analyzed statistically.
Intraoperative blood loss ranged from 5.15 to 1980 mL per kg (mean, 136 mL/kg). Massive blood loss negatively affected survival not only immediately after operation (high blood loss [HBL]:low blood loss [LBL] ratio, 85.5%:93.9% at 1 month) but also over the long term (HBL:LBL, 61.4%:76.8% at 5 years). Preoperative risk factors for massive blood loss were determined to be recipient age (<1 years), weight (<10 kg), C-reactive protein (>2 mg/dL), hematocrit (<30%), total bilirubin (>20.0 mg/dL), direct bilirubin (>16.0 mg/dL), and blood urea nitrogen levels (>30.0 mg/dL).
The risk factors associated with massive intraoperative blood loss during LDLT were identified. This is the first analysis of blood loss during LDLT at a single center. Massive blood loss is a predictor of poor prognosis in LDLT patients.
Transfusion 06/2005; 45(6):879-84. · 3.22 Impact Factor
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Takeshi Yuasa,
Hiroaki Tsuji,
Shinya Kimura,
Norimi Niwa, Kimiko Yurugi,
Hiroto Egawa,
Koichi Tanaka,
Etsuko Maruya,
Hiro-O Saji,
Hiroaki Asano,
Taira Maekawa
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ABSTRACT: Biliary atresia (BA) is a neonatal obstructive cholangiopathy characterized by a fibrosclerosing obliteration of the extrahepatic bile duct. The aim of this study was to investigate the relationship between human leukocyte antigens (HLA) and susceptibility to BA. We retrospectively analyzed 392 Japanese patients with BA and without extrahepatic anomalies who underwent living donor liver transplantations at our institute. Healthy Japanese volunteers (n = 828) served as normal controls. A significant positive association was observed between BA and HLA-DR2 (39.0% of patients vs. 30.4% of controls, odds ratio = 1.46, p = 0.029). Two-locus analyses disclosed that DR2 was not independently associated with BA, but the increased frequency of HLA-A24 and -B52 reflected the linkage disequilibrium between -A24, -B52, and -DR2. Moreover, the frequency of the haplotype HLA-A24-B52-DR2 was significantly higher in patients with BA than in the general Japanese populations described in the literature (odds ratio = 2.20, p = 0.00124). These results indicate that the gene for BA susceptibility is in close linkage disequilibrium with the HLA-A24-B52-DR2 haplotype observed in the Japanese population. We speculate that a gene at the locus close to HLA plays an important role in the pathogenesis of BA.
Human Immunology 04/2005; 66(3):295-300. · 2.84 Impact Factor
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ABSTRACT: The measurement of immunoglobulin (Ig) G blood group A/B antibody(anti-A/B) levels is important for ABO-unmatched organ recipients because the effective removal of the antibodies improves their prognosis. Currently existing methods to detect IgG anti-A/B suffer limitations owing to high costs, low throughput, and poor adaptability to automation.
We have developed a rapid means to quantitate IgG anti-A/B by surface plasmon resonance (SPR). To investigate the accuracy, a serially diluted plasma sample from a donor was measured with the SPR method. Moreover, IgG anti-A/B titers in 45 healthy volunteers were measured both by the SPR and by the standard tube test (TT) method, as were plasma samples from two ABO-unmatched organ recipients.
The change in titers when the same plasma was diluted was precisely reflected by the SPR method. The coefficients of correlation between SPR and TT methods for IgG anti-A and anti-B were 0.85 and 0.56, respectively. The SPR values also paralleled the TT values, which showed a decline in titers after the removal of antibodies by double-filtration plasmapheresis or plasma exchange.
This SPR method can be used to measure IgG anti-A/B titers in the plasma very quickly and quantitatively.
Transfusion 02/2005; 45(1):56-62. · 3.22 Impact Factor
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Surgery Today 06/1998; 28(8):857-861. · 1.22 Impact Factor
