Antibodies | New Advances in Antibody Titer Assessment Enhance Risk Stratification for ABO-Incompatible Transplantation

This article systematically reviews multiple anti-ABO antibody titer detection methods and thoroughly discusses their clinical significance in ABO-incompatible organ transplantation. It proposes that novel microarray technologies based on vascular endothelial cell ABO antigens may improve risk assessment accuracy, offering new insights for transplant immunology.

 

Literature Overview
The article 'Advancing Antibody Titer Assessment in ABO-Incompatible Transplantation', published in the journal Antibodies, reviews and summarizes the development and challenges of anti-ABO antibody titer detection techniques within the context of ABO-incompatible organ transplantation. It compares advantages and limitations of traditional methods (tube technique, column agglutination technology, flow cytometry, ELISA) and introduces emerging microarray technologies, such as glycan microarrays and CD31-ABO microarrays, which may more accurately reflect immune responses against transplanted organs. This work provides theoretical foundations and practical recommendations for standardizing anti-ABO antibody detection, holding significant clinical translational value.

Background Knowledge
ABO blood group incompatibility (ABOi) transplantation serves as a critical strategy to address donor shortages, particularly widely implemented in donor-scarce regions like Japan. Anti-ABO antibodies primarily originate from innate immunity as IgM, while anti-A/B IgG can also be detected in individuals with blood type O. Traditional titer detection relies on red blood cell agglutination assays (tube technique and column agglutination technique), but suffers from subjectivity and standardization difficulties. Recently developed microarray technologies, including glycan microarrays and CD31-ABO microarrays, target antigens more representative of ABO subtypes expressed in transplanted organs, especially endothelial cell-specific ABO type II antigens. While these newer methods offer improved objectivity and specificity, their clinical application remains limited by standardization requirements and further validation needs. The article highlights the urgent necessity for developing more precise, standardized anti-ABO antibody evaluation systems due to the lack of comparability between current methods and their inadequate reflection of immune rejection risks in transplanted organs.

 

 

Research Methods and Experimental Design
The article systematically reviews studies on anti-ABO antibody detection technologies from PubMed, Scopus, and Google Scholar, emphasizing their applications in ABO-incompatible organ transplantation. The authors compare multiple detection approaches, including traditional tube method (CTM), column agglutination technique (CAT), flow cytometry (FCM), ELISA, glycan microarrays, and CD31-ABO microarrays. The research also examines technical differences in IgM vs. IgG antibody detection across methods, as well as the necessity of dithiothreitol (DTT) treatment for IgG assessment. The CD31-ABO microarray immobilizes ABO antigens onto recombinant CD31 proteins to simulate antigen presentation on transplant organ endothelial cells, enabling more accurate antibody titer evaluation.

Key Conclusions and Perspectives

• Traditional titer detection methods (CTM and CAT) demonstrate significant inter-institutional variability due to subjective interpretation and poor standardization, limiting their reliability in transplant immunology.
• Flow cytometry (FCM) and ELISA offer higher objectivity and sensitivity, but structural discrepancies between detected antigens and native ABO subtypes expressed in transplanted organs compromise clinical relevance.
• Glycan microarrays distinguish antibody responses against different ABO subtypes, revealing low correlation between anti-A-II IgG and other subtypes, suggesting its potential role as a key driver of transplant rejection.
• The CD31-ABO microarray effectively detects antibodies targeting endothelial cell ABO antigens, demonstrating superior sensitivity and specificity compared to conventional methods, particularly for predicting acute antibody-mediated rejection (ABMR).
• Future efforts should establish unified anti-ABO antibody titer standards incorporating endothelial cell antigen specificity to optimize risk stratification and individualized immunosuppression strategies.

Research Significance and Prospects
This work provides systematic comparisons of antibody titer assessment methods for ABO-incompatible transplantation while highlighting traditional limitations. The novel CD31-ABO microarray technology promises improved detection precision in transplant immunology, potentially advancing personalized desensitization protocols and subtype-specific antibody monitoring. Prospective studies are required to validate its clinical value in transplant outcomes, alongside standardization and automation efforts to facilitate global multicenter collaborations and data comparability.

 

 

Conclusion
This article comprehensively evaluates advantages and limitations of existing anti-ABO antibody titer detection methods, emphasizing the subjectivity and clinical limitations of traditional approaches in ABOi transplantation. The CD31-ABO microarray technology, through simulating endothelial cell surface antigens, significantly enhances specificity and clinical relevance of antibody detection. Future implementation of this technology as a standardized immunology assay could provide scientific foundations for personalized desensitization therapies and postoperative antibody monitoring, ultimately improving outcomes for transplant recipients.

 

Masayuki Tasaki, Kazuhide Saito, and Kota Takahashi. Advancing Antibody Titer Assessment in ABO-Incompatible Transplantation. Antibodies.