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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.

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.

BACKGROUND: Human leukocyte antigen (HLA) is a major determinant in deciding upon solid organ histocompatibility. Donor-specific anti-HLA antibodies (Donor-specific anti-HLA antibodies (DSAs)) are always a contraindication for solid organ transplantation, and identification of DSA becomes very crucial before transplantation to provide long-term graft survival. For identification of DSA, usually, either cell-based or HLA bead-based assay is being used in laboratories. However, both cell-based and bead-based assays have certain limitations. One such common limitation is \"prozone effect,\" which can give false-negative results. Here, we would like to present a small pilot study to analyze the effect of the prozone phenomenon in the cell-based and HLA bead-based assays and its utility in histocompatibility testing. MATERIALS AND METHODS: In a series of four experiments, cell-based assay, flow cytometric cross-match (FCXM), and HLA bead-based flow cytometric panel reactive antibodies (PRAs) were performed. Single-antigen bead (SAB) testing was conducted as a first experiment on four known positives samples for anti-HLA antibody-antibodies. In the second experiment, these four samples were pooled together (called pooled sera in the text) and tested for FCXM and PRA. In the third experiment, known commercially available positive control sera were mixed with pooled positive sera (positive control sera + pooled sera) to prepare, what we have called \"positive concoction\" in the text. In the fourth experiment, the positive concoction was diluted serially (1:2, 1:4, 1:8, and 1:16) and FCXM and PRA were performed again to analyze and compare the prozone effect. RESULTS: Pooled sera did not have the expected median fluorescence intensity (MFI) values in FCXM assay, whereas the PRA was showing >90% positivity. In positive concoction, the MFI of FCXM assay was observed to be declining; however, PRA values remained almost constant. Dilutions of the pooled sera showed that MFI values of FCXM assays were increased suddenly after dilution. The highest MFI values were observed in 1:4 dilution of the sera, and then, it declined gradually, but the PRA values remained almost constant even after serial dilutions. CONCLUSION: In our experimental findings, it was clear that cell-based assay (FCXM) was more severely affected by the prozone, whereas solid-phase (flow PRA) assay remained resistant to prozone.

Abstract Introduction: Human leukocyte antigen (HLA)-matched unrelated donor (MUD) is the source of MUD transplantation (MUDT) for about 70% of patients who do not have matched related donor. To facilitate MUD search globally, there are 75 stem cell registries with more than 28 million donors registered (as of January 2017). Out of these donors, India has an insignificant representation of approximately 0.23 million. Further, Indians express high genetic variations, making it difficult to find MUD for an Indian patient. Aims and Objectives: The aim of this study is to analyze the MUD search for hematological disorder patients requiring transplant. An attempt was made to observe the MUD scenario for Indian patients requiring MUDT from accessible stem cell registries. Methods: A total of 558 patients approached Genebandhu registry and Chimera Transplant Research Foundation for MUD search over a period of 4 years requiring MUDT were included in this study. High resolution of HLA-A, -B, -C, -DRB1, and -DQB1 was used to perform MUD search through proprietary software called Prometheus and Bone Marrow Donors Worldwide (BMDW) search tool. Results: Out of 558 patients, MUD was located only for 135 (24.19%) patients. Out of these 135 patients, 91 (16.30%) patients found an MUD in global database and only 44 (7.88%) patients within India. Conclusion: This study demonstrates that building a large Indian database will not only help in increasing the chances of finding an MUD for maximum number of patients within India but also provide cost-effective treatment, in a society where cost is a vital factor.

Hematopoietic progenitor cell transplantation (HPCT) is used as a definitive treatment in hematological malignancies. For a successful HPCT, the donor and recipient should have matching human leukocyte antigens (HLAs). About 25% of patients have a chance of finding matching HLA within family, while rests 75% are dependent on voluntary stem cell donor. Globally, there are 75 stem cell registries with more than 30 million donors registered among which India represents 0.36 million. Therefore, finding a stem cell donor for Indian patient is quite difficult. The aim of the present study is to discuss the significance of voluntary stem cell donor recruitment drive and also to guide the drive organizers and their team for effectively organizing the drive to increase the database of such donors. Voluntary stem cell donor recruitment drives are conducted to spread awareness among the people and motivate them to register as a donor. Once the donors have given their consent, the sample is taken and sent to laboratory for HLA typing and the result is uploaded in World Marrow Donor Association, an international association of member to find the best possible matches for patients with hematological disorders. Genebandhu has organized over 127 recruitment camps since 2012 and recruited 13,000 voluntary stem cell donors. HLA typing of 7446 donors has been completed. Out of this small number of typed donors, 11 lifesaving HPCTs have been successfully facilitated. Here, we have demonstrated guidelines along with steps to organize voluntary stem cell donors recruitment drive that is needed to increase number of donors, thus increasing significantly the chances of saving many vital lives.

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.

Lethality of Plasmodium falciparum caused malaria results from ‘cytoadherence’, which is mainly effected by exported Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family. Several exported P . falciparum proteins (exportome) including chaperones alongside cholesterol rich microdomains are crucial for PfEMP1 translocation to infected erythrocyte surface. An exported Hsp40 (heat shock protein 40) ‘PFA0660w’ functions as a co-chaperone of ‘PfHsp70-x’, and these co-localize to specialized intracellular mobile structures termed J-dots. Our studies attempt to understand the function of PFA0660w-PfHsp70-x chaperone pair using recombinant proteins. Biochemical assays reveal that N and C-terminal domains of PFA0660w and PfHsp70-x respectively are critical for their activity. We show the novel direct interaction of PfHsp70-x with the cytoplasmic tail of PfEMP1, and binding of PFA0660w with cholesterol. PFA0660w operates both as a chaperone and lipid binding molecule via its separate substrate and cholesterol binding sites. PfHsp70-x interacts with cholesterol bound PFA0660w and PfEMP1 simultaneously in vitro to form a complex. Collectively, our results and the past literature support the hypothesis that PFA0660w-PfHsp70-x chaperone pair assists PfEMP1 transport across the host erythrocyte through cholesterol containing ‘J-dots’. These findings further the understanding of PfEMP1 export in malaria parasites, though their in vivo validation remains to be performed.

Introduction: In India, 90% kidneys for transplantation are obtained from living donor while only 10% come from deceased donors. Since the rate of living organ donors is high, it therefore leads to the problem of organ trafficking.To minimize the chances of organ trafficking, the Transplantation of Human Organ Act (THOA) 2014 was enacted in India that makes it mandatory to prove the relationship between patient and donor by DNA testing. The present study was undertaken to evaluate the degree of matching between maternally related patients and donors, performed using mitochondrial DNA (mtDNA).Methods: After taking an informed consent, a total of 84 subjects were recruited in the study, 42 kidney transplant recipients and 42 their corresponding donors. An attempt was made to establish and confirm the claimed relationship betweenrecipient and donor using mtDNA analysis. Results: Out of the total 42 cases, mtDNA analysis supported the claimed relationship in 33 (78.57%) cases, whereas in 9 (21.42%) cases claimed relationship could not be supported. Conclusion: mtDNA can be used as valuable tool to support the claimed relationships of maternal lineage. It is important that more and more organ transplant physicians, surgeons and committees are made aware of this diagnostic modality.

Abstract Plasmodium falciparum (Pf) proteins exported to infected erythrocytes are key effectors of malaria pathogenesis. These include the PfEMP1 (Pf erythrocyte membrane protein 1) protein family that affects malaria-related mortality through cytoadhesion and parasite immune evasion. Parasites also induce membranous structures called Maurer's clefts (MC) in infected erythrocytes to compensate the lack of host protein synthetic and export machinery. PfEMP1 export is mediated by a myriad of proteins including Pf skeleton binding protein 1 (PfSBP1) and PF70, a hypothetical 16 family member. Here, we aim to understand the function of the only other exported PEXEL-positive hyp16 member ‘PfJ23’. Our in vitro and in silico data suggest this protein to be mostly α-helical while displaying different oligomeric forms under reducing and non-reducing conditions. We show coherent expression, partial co-localization and direct interaction of purified PfSBP1 with recombinant and native PfJ23. Recombinant and parasite-expressed PfJ23 also bind to the cytoplasmic tail of PfEMP1, and they seem to partly co-localize during parasite development. Both novel binding partners interact simultaneously with PfJ23 in vitro to form a complex. Our results suggest a probable role for PfJ23 in export of PEXEL-negative proteins like PfSBP1 and PfEMP1, furthering our understanding of malaria biology. Plasmodium falciparum protein PfJ23 hosts distinct binding sites for major virulence factor ‘PfEMP1’ and Maurer's cleft marker ‘PfSBP1’.

Eukaryotic proteomes harbour repetitive stretches of amino acids that may play critical roles in the biology of that organism. While several tandem repeats (TR) are known to contribute to protein structure and function, information about the vast majority of repeat regions remains obscure. In this article, we have analysed the repeat content of different Plasmodium species and found the leading human malaria-causing P. falciparum (Pf) and P. vivax to be exceptionally rich in TR regions (>40% TR containing proteins). Detailed analysis of Pf ‘repetome’ showed this intracellular parasite to carry longer TRs, several of which were present in exported proteins important for parasite survival and immune evasion. The repeat regions of Pf were enriched in acidic amino acids and asparagine (Asn), where Asn was more abundant in short and intermediate TRs, suggesting an evolutionary bias influenced by replication slippage and positive selection. Gene ontology analysis of TR containing Pf proteins helped us to understand their cellular localization along with the molecular and biological processes they are involved in. The Pf variable surface antigen families with roles in important pathogenic processes like cytoadherence, immune evasion etc. had low repeat content present within seroreactive peptides. Three-dimensional structure predictions of TR regions revealed several repeats to adopt ordered super-secondary conformations that are known to facilitate intermolecular interactions. Overall, this is a comprehensive study attempting to gain insights on the importance of TRs in malaria parasite biology and suggests a novel route to understanding protein function through the characterization of repeat content.