scholarly journals Novel Diagnostic and Therapeutic Approach to Antibody-Mediated Rejections in Heart Transplantation

2020 ◽  
Author(s):  
Takuya Watanabe ◽  
Norihide Fukushima
Keyword(s):  
Flow Cytometry ◽  
Heart Transplantation ◽  
Membrane Attack Complex ◽  
Hla Antigens ◽  
Human Leukocyte ◽  
Classical Pathway ◽  
Cytotoxicity Test ◽  
Solid Organ ◽  
Heart Graft ◽  
Cardiac Graft

Despite the improvement of immunosuppressive therapy in heart transplantation (HTx), antibody-mediated rejection (AMR) is still a great obstacle to prolong cardiac graft survival. Anti-donor-specific antibodies (DSAs), especially anti-donor human leukocyte antigen (HLA) antibody, lead to heart graft failure resulting in hemodynamic consequence and often in the recipient death. To prevent hyperacute rejection, prospective complement-dependent cytotoxicity test has been performed in every cardiac donor in Japan. But in other solid organ transplantations, flow cytometry crossmatch has been recently recommended to crossmatch to select the recipient in Japan as well as the world. However, flow cytometry is too sensitive to select the recipient, because not all DSAs determined by flow cytometry are cytotoxic to the cardiac graft. On the first complement classical pathway, alloantibodies bind to HLA antigens on cells of the graft and then recruit C1q, which is essential to make membrane attack complex and kill the cell. We review a role of the novel monitoring method of complement pathway regarding C1q in occurrence of AMR and its diagnostic and therapeutic significance in managing AMR in HTx.

scholarly journals The Presence of Anti-HLA Antibodies before and after Allogeneic Hematopoietic Stem Cells Transplantation from HLA-Mismatched Unrelated Donors

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Anna Koclega ◽  
Miroslaw Markiewicz ◽  
Urszula Siekiera ◽  
Alicja Dobrowolska ◽  
Mizia Sylwia ◽  
...  
Keyword(s):  
Solid Organ Transplantation ◽  
Hla Antigens ◽  
Human Leukocyte ◽  
Solid Organ ◽  
No Donor ◽  
Hla Antibodies ◽  
Hematopoietic Stem ◽  
Before And After ◽  
Unrelated Donors ◽  
Hematopoietic Stem Cells Transplantation

Although anti-human leukocyte antigen antibodies (anti-HLA Abs) are important factors responsible for graft rejection in solid organ transplantation and play a role in post-transfusion complications, their role in allogeneic hematopoietic stem cell transplantation (allo-HSCT) has not been finally defined. Enormous polymorphism of HLA-genes, their immunogenicity and heterogeneity of antibodies, as well as the growing number of allo-HSCTs from partially HLA-mismatched donors, increase the probability that anti-HLA antibodies could be important factors responsible for the treatment outcomes. We have examined the incidence of anti-HLA antibodies in a group of 30 allo-HSCT recipients from HLA-mismatched unrelated donors. Anti-HLA Abs were identified in sera collected before and after allo-HSCT. We have used automated DynaChip assay utilizing microchips bearing purified class I and II HLA antigens for detection of anti-HLA Abs. We have detected anit-HLA antibodies against HLA-A, B, C, DR, DQ and DP, but no donor or recipient-specific anti-HLA Abs were detected in the studied group. The preliminary results indicate that anti-HLA antibodies are present before and after allo-HSCT in HLA-mismatched recipients.

scholarly journals Donor-recipient Matching in Heart Transplantation

2020 ◽  
Vol 14 (1) ◽  
pp. 42-47
Author(s):  
Aleksandra Oprzędkiewicz ◽  
Hubert Mado ◽  
Wioletta Szczurek ◽  
Mariusz Gąsior ◽  
Bożena Szyguła-Jurkiewicz
Keyword(s):  
Heart Transplantation ◽  
Perioperative Complications ◽  
Hla Antigens ◽  
Human Leukocyte ◽  
Abo Blood Group ◽  
Leukocyte Antigen ◽  
End Stage Heart Failure ◽  
End Stage ◽  
The Impact

Heart transplantation remains the treatment of choice for end-stage Heart Failure (HF). Due to the shortage of organs for transplantation and the occurrence of perioperative complications, a key problem is donor matching, which should result in increased survival and improved quality of life for patients. The success of this procedure depends on various parameters such as gender, weight, ABO blood group and Human Leukocyte Antigen (HLA) system of both the recipient and the donor. Furthermore, non-HLA antigens may also be valuable in donor-recipient matching. The aim of this article is to summarize the recent knowledge on the impact of various factors on accurate donor-recipient matching to heart transplantation.

POSITIVE FLOW CYTOMETRY CROSSMATCHES AND DONOR-SPECIFIC HLA ANTIBODIES MAY NOT BE CONTRAINDICATIONS TO HEART TRANSPLANTATION

2010 ◽  
Vol 90 ◽  
pp. 447
Author(s):  
R. H. Kerman ◽  
R. Radovancevic ◽  
P. Allison ◽  
E. McKissick ◽  
J. G. Saltarrelli ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Heart Transplantation ◽  
Hla Antibodies

Abstract 13626: Human Leukocyte Antigen A*30 is Associated With Congenital Heart Disease

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Horacio G Carvajal ◽  
Fei Wan ◽  
Anoop K Brar ◽  
Chang Liu ◽  
Pirooz Eghtesady
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Congenital Heart ◽  
Large Population ◽  
Population Sample ◽  
Hla Antigens ◽  
Human Leukocyte ◽  
Hla Typing ◽  
Race And Gender ◽  
And Gender

Introduction: Congenital heart disease (CHD) arises from many etiologies, ranging from genetic to environmental exposures, such as viral infections. The human leukocyte antigens (HLA) play an important role in the immune response to pathogens. HLA has been extensively explored and linked with several diseases; no such investigations, however, have been done in context of CHD. Hypothesis: We sought to identify potential HLA associations with CHD in a large population sample with molecular-based HLA typing. Methods: Available data on race, gender, HLA-A, B, and DRB1 typing (1-field, antigen level) was collected from the 2,349 patients in the United Network for Organ Sharing (UNOS) database undergoing heart transplant due to CHD between 2005 and 2017. These were compared to all 80,893 deceased kidney donors in the same period. Nominal variables were compared with Pearson’s chi-square, and logistic regression was used to compare all HLA antigens between groups, adjusting for race and gender. The false discovery rate was used to control for multiple comparisons, with adjusted p-values <0.05 considered significant. Results: There were 14 HLA-A, 25 HLA-B, and 14 HLA-DRB1 antigens with an overall frequency of 1% or higher. The frequency of HLA-A*30, B*44, and DRB1*08 differed significantly between groups (Table 1). Unconditional regression showed significantly increased odds of CHD in patients with HLA-A*30 and HLA-DRB1*08, as well as significantly lower odds in those with HLA-B*44 (Table 1). The demographics between groups were comparable, with the exception of fewer Caucasians in the cases (CHD 60.7% vs controls 65.6%, p=0.026). When adjusted for race and gender, only HLA-A*30 remained statistically significant. Conclusions: HLA-A*30 appears to be linked with CHD independent of race. Further analyses with detailed CHD diagnoses and high-resolution HLA typing data are needed to explore potential associations between specific cardiac defects and HLA at the allele level.

scholarly journals HLA-B27 phenotyping with flow cytometry: further improvement by multiple monoclonal antibodies

1997 ◽  
Vol 43 (10) ◽  
pp. 1975-1981 ◽  
Author(s):  
Johannes J M L Hoffmann ◽  
Willy C M Janssen
Keyword(s):  
Flow Cytometry ◽  
Internal Control ◽  
Hla Antigens ◽  
Immunofluorescence Assay ◽  
Direct Immunofluorescence ◽  
Hla B27 ◽  
Roc Curve Analysis ◽  
Cross Reactions ◽  
Flow Cytometric Method ◽  
Direct Immunofluorescence Assay

Abstract To establish the optimal flow cytometric method for HLA-B27 phenotyping, we compared several strategies, using three monoclonal anti-B27 antibodies (from the HLA-ABC-m3, GS145.2, and FD705 clones). We used a triple-color direct immunofluorescence assay, including a T-lymphocyte-specific antibody as an internal control and an anti-HLA-Bw4 antibody. Blood samples from &gt;400 subjects were tested. From ROC curve analysis none of the three antibodies appeared to be suitable for use as a single typing reagent. The efficiency of the test was affected by cross-reactions with other HLA antigens, notably the HLA-B7 antigen. Preincubation with anti-B7 serum efficiently inhibited this cross-reaction and raised the test efficiency considerably. We concluded that none of the anti-B27 antibodies investigated is suitable for use as a single typing reagent. Additional typing of Bw4 is not valuable, whereas inhibition of cross-reactions due to the B7 antigen will considerably improve the performance of the test. We recommend that two different monoclonal anti-B27 antibodies be used for accurate and reliable HLA-B27 phenotyping with flow cytometry.

Flow Cytometry: An Important Diagnostic Tool in Critically Ill Preterm Neonates with Suspected Sepsis

2020 ◽  
Author(s):  
Sneha Goswami ◽  
Richa Gupta ◽  
Siddarth Ramji
Keyword(s):  
Flow Cytometry ◽  
Blood Culture ◽  
Clinical Signs ◽  
Human Leukocyte ◽  
Preterm Neonates ◽  
Suspected Sepsis ◽  
Predictive Values ◽  
Flow Cytometric ◽  
Time Flow ◽  
Culture Positive

Objective Sepsis is a major cause of neonatal mortality. The gold standard for diagnosis is blood culture which suffers from low sensitivity and huge turn-around time. Flow cytometry has been extensively applied to malignant disorders and is an upcoming tool for diagnosis of nonmalignant disorders due to its rapidity and accuracy in detecting cells, cell products, and their functional states. The aim of this study was to investigate the utility of flow cytometric expression of neutrophil CD64, monocyte human leukocyte antigen (HLA-DR) and CD16 in diagnosis in suspected preterm neonates. Study Design In total, 100 preterm neonates with clinical signs of sepsis were enrolled in the study. Blood culture, C-reactive protein (CRP) and flow cytometry for nCD64, mHLA-DR, and mCD16 were performed. The neonates were divided into two groups: culture positive and culture negative and CRP and flow cytometric findings compared. ROC analysis was performed to determine the best cut-off for nCD64, mHLA-DR, and mCD16 values along with estimation of sensitivity, specificity, and predictive values. Probability of <0.05 was taken as significant. Results Out of the 100 enrolled neonates, 34 (34%) were culture positive. CRP was not found to be significantly different in the two groups. Expression of nCD64 (p = 0.03) was significantly upregulated in the blood culture positive cases with a cut-off mean fluorescence intensity (MFI) value = 4.72 and sensitivity of 92% and specificity of 52%. Expression of mCD16 (p = 0.02) was also upregulated in the blood culture positive cases with a cut-off MFI value = 4.9, with sensitivity of 41%, specificity of 83%. Conclusion The study concluded that nCD64 and mCD16 can be potential biomarkers for early diagnosis of neonatal sepsis with a high sensitivity and specificity. Key Points

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