Negative effects of donor specific anti-HLA antibody on poor hematopoietic recovery in patients with hematological diseases receiving haploidentical stem cell transplantation and rituximab for desensitization / 中华内科杂志

Objective:To investigate the incidences and risk factors of poor hematopoietic reconstitution (PHR) in patients with hematological diseases who underwent haploidentical allograft and were treated with rituximab for desensitization.Methods:Eight-three donor specific anti-HLA antibody (DSA, 2000 ≤MFI<10 000) positive patients who underwent haploidentical allograft were prospectively enrolled. Rituximab (375 mg/m 2) was used for desensitization day-3 of conditioning regimen. Incidence and factors associated with PHR, including primary poor graft function and prolonged thrombocytopenia, were investigated. Results:There were 22 males and 61 females with a median age of 39(range: 1-65) years. Kaplan-Meier analysis showed that the 100 day cumulative incidences of neutrophil and platelet engraftment were 93.0% and 90.7%, respectively. The incidences of PHR were 14.7%. The 3-year relapse rate, non-relapse mortality (NRM) rate, event-free survival (EFS), leukemia-free survival (DFS) and overall survival (OS) were 6.5%, 15.1%, 70.8%, 79.4% and 79.4%, respectively. Patients with DSA MFI<5 000 (group A, n=46) experienced lower PHR (4.4% vs. 27.5%, P=0.003), and higher 3-year EFS (79.5% vs. 59.8%, P=0.020) compared to those with DSA MFI≥5 000 (group B, n=37). Multivariate analysis showed that DSA MFI≥5 000 was correlated with PHR ( HR=6.101, P=0.021). PHR was associated with higher NRM ( HR=4.110, P=0.026), lower DFS ( HR=3.656, P=0.019) and OS ( HR=3.656, P=0.019). Conclusion:Our data suggest that high pre-transplant DSA level is a risk factor for PHR in patients with hematological diseases receiving haploidentical allograft and rituximab for desensitization.

Research advances on haploidentical hematopoietic stem cell transplantation in the treatment of severe aplastic anemia in children / 中国当代儿科杂志

Haploidentical hematopoietic stem cell transplantation is a recommended alternative therapy for children with severe aplastic anemia who lack a human leukocyte antigen (HLA)-identical sibling donor and do not respond well to immunosuppressive therapy; however, due to non-identical HLA, the patients may have donor-specific anti-HLA antibody, which may lead to a relatively high incidence rate of poor graft function. Compared with HLA-identical transplantation, conditioning regimen for haploidentical transplantation still needs to be explored. This article reviews the detection and treatment of donor-specific anti-HLA antibody, the selection of conditioning regimen, and the mechanism and treatment of poor graft function in haploidentical hematopoietic stem cell transplantation.

Clinical Impact of Pre-transplant Antibodies Against Angiotensin II Type I Receptor and Major Histocompatibility Complex Class I-Related Chain A in Kidney Transplant Patients

BACKGROUND: Evidence of antibody-mediated injury in the absence of donor-specific HLA antibodies (HLA-DSA) has recently emerged, suggesting a role of antibodies in targeting non-HLA antigens expressed on renal allograft tissue. However, the clinical significance of pre-transplant non-HLA antibodies remains unclear. We compared the histological and clinical impact of pre-transplant HLA-DSA and non-HLA antibodies, especially angiotensin II type I receptor (anti-AT1R) and MHC class I-related chain A (anti-MICA), in kidney transplant patients. METHODS: Pre-transplant HLA-DSA, anti-AT1R, and anti-MICA were retrospectively examined in 359 kidney transplant patients to determine the effect of each antibody on allograft survival and clinical characteristics. RESULTS: Pre-transplant HLA-DSA, anti-AT1R, and anti-MICA were detected in 37 (10.3%), 174 (48.5%), and 50 patients (13.9%), respectively. Post-transplant antibody-mediated rejection was associated with a pre-transplant HLA-DSA (+) status only. The development of microvascular inflammation (MVI) was associated with pre-transplant HLA-DSA (P=0.001) and anti-AT1R (P=0.036). Anti-AT1R (+) patients had significantly lower allograft survival compared with anti-AT1R (−) patients (P=0.042). Only pre-transplant anti-AT1R positivity was an independent risk factor for allograft failure (hazard ratio 4.824, confidence interval 1.017–24.888; P=0.038). MVI was the most common histological feature of allograft failure in patients with pre-transplant anti-AT1R. CONCLUSIONS: Pre-transplant anti-AT1R is an important risk factor for allograft failure, which may be mediated by MVI induction in the allograft tissue.

A Case Report of Transfusion-Related Acute Lung Injury Induced in the Patient with HLA Antibody after Fresh Frozen Plasma Transfusion / 대한수혈학회지

Development of transfusion-related acute lung injury (TRALI), a non-cardiogenic pulmonary edema, after blood transfusion, is a rare but potentially leading cause of mortality from blood transfusion. We report on a case of TRALI in a 51-year male with acute calculous cholecystitis and liver cirrhosis. As preoperative treatment, he was given ten units of fresh frozen plasma (FFP) for 3 days before the operation. During the transfusion of the 10th unit of FFP, he experienced a sudden onset of hemoptysis, tachypnea, tachycardia, and cyanosis. Bilateral pulmonary infiltration not observed on the chest X-ray at the visit was newly developed. There was no evidence of volume overload but severe hypoxemia. Blood transfusion was stopped and he recovered fully after 8 days of oxygen therapy through a nasal cannula. Although HLA and HNA antibodies were not detected in the donor's blood, HLA antibodies (A2, B57, B58) were detected in the patient's blood. We reported this meaningful case of TRALI that occurred after transfusion of only fresh frozen plasma which did not contain human leukocyte antibody in a patient with HLA antibody.

Anti-HLA and anti-MICA antibodies are positively correlated with transplanted kidney dysfunction / 中华微生物学和免疫学杂志

Objective To study the correlation between transplanted kidney dysfunction and oc-currence of the panel reactive antibody ( PRA, also referred as anti-HLA antibody ) and anti-Major-Histo-compatibility-Complex class Ⅰrelated chain A (MICA) antibody.Methods The tests for detecting PRA and anti-MICA antibody were performed on 679 renal transplant patients from December , 2009 to June, 2010 who received transplantation before 2008 in Beijing Friendship Hospital .Enzyme-Linked Immunosor-bent Assay ( ELISA) was used to detect anti-HLA antibody using LAT-1240 ( OneLambda Inc .) .MICA Ab-Scan Kit was adopted to detect anti-MICA antibody .Continuous observation of graft function was conducted . Results 108 out of 679 patients showed anti-HLA antibody and/or anti-MICA antibody positive results . Among them, 81 patients were positive only for anti-HLA antibody, 18 patients were positive only for anti-MICA antibody and other 9 patients showed anti-HLA and anti-MICA antibodies double positive .Among all of the kidney transplant patients with a failed or decreased renal function , 71 patients were positive for anti-HLA antibody;16 patients were positive for anti-MICA antibody;and other 9 patients were positive for both anti-HLA and anti-MICA antibodies .The results demonstrated that anti-HLA and anti-MICA antibodies af-fected the renal functions in patient with renal transplantation (χ2 =353.92, P <0.001).Conclusion Anti-HLA and MICA antibodies showed significant positive correlations with chronic allograft failure in the patients with renal transplantation .

A case of transfusion-related acute lung injury induced by anti-human leukocyte antigen antibodies in acute leukemia

Transfusion-related acute lung injury (TRALI) is a noncardiogenic pulmonary edema that occurs during or within 6 hours after transfusion. Risk factors for TRALI, which is relatively common in critically ill patients, include recent surgery, hematologic malignancy, and sepsis. Here, we report a case of TRALI induced by anti-human leukocyte antigen (anti-HLA) class II antibodies (HLA-DR) occurring after transfusion of platelet concentrates in a patient with acute leukemia. Although most patients with TRALI show improvement within 48-96 hours, our patient's condition rapidly worsened, and he did not respond to supportive treatment. TRALI is a relatively common and serious adverse transfusion reaction that requires prompt diagnosis and management.

Comparison of HLA antibody incidence in old, middle and young age patients / 中华微生物学和免疫学杂志

Objective To investigate the HLA antibody incidence and type renal recipients with different age, and to study the echaracteristics in different age patients, for clinical reference to forecast renal rejection in different age patients. Methods With serum dated from January 2006 to June 2008, patients were classified into three groups: young group, with age below 35 years; middle age group, with age from 36 to 50 years; and old group, with age above 50 years. Penel reactive antibody (PRA) were detected using ELISA. Results Pretransplant HLA antibody incidences in the young, middle age, old group were 18.18%, 23.00% and 6.19%, respectively. In young group, HLA antibody incidences were 5.59% and 8.51% in male and female respectively. In middle age group, they were 21.30% and 25.38% in male and female respectively. In old group, they were 11.36% and 25.00% respectively. HLA Ⅰ and HLA Ⅰ + Ⅱ antibodies were mainly found in all the three groups in pretansplant. Conclusion HLA Ⅰ and HLA Ⅰ + Ⅱ antibodies were mainly found in pretransplant. Antibody incidence was higher in patients who had more than once renal transplant than that in transfusion and pregnancy female. Antibody incidence is higher in female than that in male.

Two Cases of Transfusion-related Acute Lung Injury Triggered by HLA and Anti-HLA Antibody Reaction

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.

Allograft Immune Reaction of Kidney Transplantation Part 2. Immunosuppression and Methods to Assess Alloimmunity

For solid organ transplant, ABO blood type of donor and recipient should be compatible in principle. Recent improvement of immunosuppressant made HLA typing not so important while no-mismatch transplant still shows the longest graft survival. PRA(panel reactive antibody) test is to screen and identify recipients with HLA sensitization. When solid organ transplant is scheduled, cross-match test of donor cell and recipient serum should be performed and positive result of cross-match prohibits transplantation. Donor specific antibody (DSA) test can predict the severity of recipient immune reaction against donor organ. Today's mainstay of allograft immunosuppressant regimen is triple therapy of steroid, calcineurin inhibitor(cyclosporine, tacrolimus), azathioprine or mycophenolate mofetil(MMF). Antibody induction using Thymoglobulin or anti-IL-2 receptor antibody(basiliximab or daclizumab) is frequently practiced as well.

A Case of Neonatal Alloimmune Thrombocytopenia due to Anti-HLA-B62+B75 / 대한수혈학회지

We encountered a case of neonatal alloimmune thrombocytopenia (NAIT) due to anti-HLA-B62+B75. We incidentally find thrombocytopenia (14,000/uL at birth and decreased to 4,000/uL at 12 hours after birth) in a female fullterm neonate. Petechial skin lesions are developed on her back and buttock at second day of birth. Her mother suffered from preeclamsia during her last trimester, but her platelet count was 167,000/uL and she had no history of abnormal bleeding. Anti-HLA-B62+B75 antibody was identified in mother's serum by panel reactive antibody test and was reactive with father's platelet by mixed passive hemagglutination assay. Platelet concentrate was transfused at the second and 5th days and patient's platelet count rose up to 58,000/uL just after transfusion but decreased to 21,000/uL eventually. From the 8th day, gamma globulin (1g/kg/day) was started intravenously for 3 days and platelet count rose up to 128,000/uL at 13th day and remained within normal limit thereafter.

A Case of Neonatal Alloimmune Thrombodytopenia Due to Anti - HLA Antibody

Anti-HLA antibody related neonatal thrombocytopenia is an uncommon disorder caused by platelet antigen incompatibility between mother and fetus in Korea. Mothers who lack the specific platelet antigen produce the IgG against the platelet antigen which the fetus inherits from the father. These IgG antibodies are then transported across the placenta into the fetal circulation where they lead to the destruction of fetal platelets. We report a case of neonatal alloimmune thrombocytopenia related with anti-HLA antibody in second baby of dizygotic twin who had petechia on trunk and platelet count 43,000/mm. Initially, mother and twin showed the positives in antiplatelet antibodies. In microlym- phocytotoxic test at 6 months of age, anti-HLA antibodies was negative in twins but anti-HLA A2, A24 was positive in their mother. The patient was treated with intravenous immunoglobulin and clinically improved and her platelet count was norrnalized.

A Case of Saethre - Chotzen Syndrome

Anti-HLA antibody related neonatal thrombocytopenia is an uncommon disorder caused by platelet antigen incompatibility between mother and fetus in Korea. Mothers who lack the specific platelet antigen produce the IgG against the platelet antigen which the fetus inherits from the father. These IgG antibodies are then transported across the placenta into the fetal circulation where they lead to the destruction of fetal platelets. We report a case of neonatal alloimmune thrombocytopenia related with anti-HLA antibody in second baby of dizygotic twin who had petechia on trunk and platelet count 43,000/mm. Initially, mother and twin showed the positives in antiplatelet antibodies. In microlym- phocytotoxic test at 6 months of age, anti-HLA antibodies was negative in twins but anti-HLA A2, A24 was positive in their mother. The patient was treated with intravenous immunoglobulin and clinically improved and her platelet count was norrnalized.