Histocompatibility testing is pivotal in any renal transplantation workup, aimed at enhancing prospective donor recipient compatibility and improving transplant outcomes. The evolution and advancement of histocompatibility testing, particularly HLA typing, have significantly improved its precision. This study outlines the historical progression from serologic to DNA-based HLA typing, emphasizing the role of HLA proteins in immune response. Anti-HLA antibodies, targeting HLA proteins, pose challenges in renal transplantation. Monitoring and managing these antibodies are critical for renal transplant success. Complement-dependent cytotoxicity crossmatch and flow cytometry crossmatch are essential techniques for assessing donor–recipient compatibility. Panel-reactive antibody assesses antibodies against a panel of donor antigens, often HLA. Higher PRA levels (percentage) complicate donor matching, requiring specialized protocols. Virtual crossmatch evaluates recipient anti-HLA antibodies against potential donors through synthetic beads. This approach predicts crossmatch outcomes by comparing antibody profiles, offering a valuable tool for the risk assessment of renal transplantation. Despite advancements, a comprehensive understanding of alloreactive immune responses requires a combination of assays, emphasizing the importance of a multifaceted approach in histocompatibility testing. This is an attempt to compile the relevant information, providing a basis for comparison in a clear and foundational format for histocompatibility testing laboratories.

Antibody-mediated rejection is a critical factor in acute and chronic allograft rejection, with Human Leukocyte Antigen as the primary target of the humoral immune response in kidney transplants. In addition to HLA antibodies, non-HLA Abs also play a significant role in AMR. These non-HLA Abs, which can target either autoantigens or alloantigens, may be present pre-transplantation or develop post-transplant. They are associated with various types of allograft injury. The major non-HLA Abs include those directed against the angiotensin II type 1 receptor, endothelin type A receptor, and MICA, as well as other antigens such as vimentin, collagens, and anti-endothelial cell antibodies. Factors such as ischemia, reperfusion injury, and calcineurin inhibitor toxicity can trigger the pathogenic activity of these Abs. The mechanisms underlying non-HLA Ab production are not yet fully understood but are thought to involve endothelial injury and the exposure of neoantigens. Research indicates that these non-HLA Abs can cause graft injury through both complement-dependent and complement-independent pathways. However, detecting non-HLA Abs remains a challenge due to the lack of reliable diagnostic tools. Current treatment strategies for managing the effects of pathogenic non-HLA Abs include intravenous immunoglobulin, plasmapheresis, rituximab, and bortezomib. Early identification of high-risk patients and timely intervention are crucial to preventing graft failure. This review examines the development, mechanisms, and clinical significance of non-HLA Abs in kidney transplantation, highlighting the need for improved diagnostic methods and tailored therapeutic approaches.

Introduction: Numerous studies have concentrated on specific populations to explore the extensive polymorphism of class I and II HLA genes. This genetic diversity is crucial for various applications, such as advancing transplantation immunology, understanding genetic population patterns, and uncovering the pathways of different diseases. Objective: The objective of the present study was to determine and analyse the frequencies of class I (HLA-A, HLA-B and, HLA-C), and class II (HLA-DRB1, and HLA-DQB1) genes in the North Indian population. Material and Methods: To achieve the objective of the study, buccal swab samples from 3648 individuals were collected. All these samples were subsequently tested for the HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 genes using the polymerase chain reaction (PCR) sequence-specific oligonucleotide probe (SSOP) typing method and typing result were analyzed to estimate class I and II allele frequencies. Results: In the present study, we have identified 16 different variants of HLA-A genes, 28 variants of HLA-B genes, 13 variations of HLA-C genes, 14 variants of HLA-DRB1 genes, and 6 variants of HLA-DQB1 genes. Furthermore, HLA-A*11, HLA-B*35, HLA-C*07, HLA-DRB1*15, and DQB1*06 were observed to be the most frequent alleles within the studied population. Discussion & Conclusions: The findings of the studied population highlight the variability exhibited by the HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 genes in the North Indian population. Additionally, this also highlights the importance of testing and understanding the prevalence of these specific HLA genes in these populations, which has a greater relevance in both hematopoietic stem cell and solid organ transplantation as well as disease association studies.

Though the role of clinical histocompatibility testing is fundamental to successful transplant, systematic risk assessment and mitigation strategies remain underutilised in this domain. This review addresses risk identification, analysis, and control measures across the pre-analytical, analytical, and post-analytical phases of clinical histocompatibility testing, in line with international standards such as ISO 15189:2022. A structured, risk-based quality management system (QMS) is imperative for ensuring accurate testing, timely reporting, and subsequently optimal transplant outcomes. Future directions include leveraging digital tools and fostering a culture of continuous improvement in histocompatibility laboratories.

Background/Objectives: Epitope-based matching has emerged as a refined approach for assessing donor–recipient compatibility in renal transplantation. However, limited data are available on HLA Class I epitope distribution among Indian patients, particularly from northern India, where substantial allelic diversity is known to influence immunological risk. Methods: This retrospective analysis evaluated HLA Class I single-antigen bead (SAB) antibody data from 218 consecutive renal-transplant candidates who tested positive for anti-HLA antibodies between July 2018 and September 2024. HLA Class I epitopes were identified and analyzed using MATCH IT Antibody Software (Immucor, version 1.5.0). Demographic variables and sensitization history (previous transplant, transfusion, pregnancy) were reviewed. Results: A total of 504 distinct epitopes were identified, with 65GK and 163LG emerging as the most frequent motifs. The predominance of these epitopes mirrors the high prevalence of alleles such as HLA-A*24 and HLA-B*35 reported in North-Indian populations. The data suggest a strong influence of regional allele architecture on the immunogenic epitope landscape. Conclusions: This study provides the first baseline characterization of HLA Class I epitope distribution among northern-Indian renal-transplant candidates. The findings emphasize the need for establishing population-specific HLA epitope databases and highlight the potential of epitope-based matching to enhance donor selection and minimize immunological risk in Indian transplantation programs.

Hematopoietic stem cell transplantation (HSCT) offers a potentially curative option for a range of malignant and non-malignant hematological disorders. However, only approximately 25-30% of patients have access to a human leukocyte antigen (HLA)-matched related donor (MRD), necessitating alternative donor approaches, including matched unrelated donor (MUD) and haploidentical transplantation. Although advances in haploidentical HSCT have substantially improved donor availability, MUD HSCT continues to play an important role in selected high-risk hematological malignancies where optimal HLA matching may influence transplant outcomes. Volunteer stem cell donor registries (VSCDRs) were established to address this unmet need and have evolved into a globally interconnected network facilitating international donor searches and cross-border hematopoietic stem cell (HSC) exchange. According to recent World Marrow Donor Association (WMDA) reports, the global donor pool exceeds 44 million volunteer donors and 0.76 million cord blood units (CBUs). Despite this expansion, significant disparities persist for genetically diverse and underrepresented populations, particularly in South Asia. India faces unique challenges related to extensive HLA heterogeneity, limited indigenous donor representation, prolonged MUD search timelines, and donor attrition. Recent studies suggest that fully MUD probabilities for Indian patients remain substantially lower than those reported for populations of European ancestry. This review summarizes the global evolution of VSCDRs, examines the current landscape of Indian registries, and discusses key operational, economic, and infrastructural challenges affecting MUD HSCT in India. Potential strategies, including targeted donor recruitment, improved donor retention programs, national registry integration, and broader adoption of next-generation sequencing (NGS)-based high-resolution (HR) HLA typing, are also discussed as approaches to improve donor availability and equitable access to HSCT in India.