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Clinical and Experimental Nephrology Jul 2024Extracellular vesicles (EVs) have received considerable attention as ideal biomarkers for kidney diseases. Most reports have focused on urinary EVs, that are mainly...
BACKGROUND
Extracellular vesicles (EVs) have received considerable attention as ideal biomarkers for kidney diseases. Most reports have focused on urinary EVs, that are mainly derived from the cells in the urinary tract. However, the detection and the application of kidney-derived EVs in plasma remains uncertain.
METHODS
We examined the kidney-derived small EVs (sEVs) in plasma that were supposedly released from renal mesangial and glomerular endothelial cells, using clinical samples from healthy controls and patients with kidney transplants. Plasma from healthy controls underwent ultracentrifugation, followed by on-bead flow cytometry, targeting α8 integrin, an antigen-specific to mesangial cells. To confirm the presence of kidney-derived sEVs in peripheral blood, plasma from ABO-incompatible kidney transplant recipients was ultracentrifuged, followed by western blotting for donor blood type antigens.
RESULTS
Immunohistochemistry and immunoelectron microscopy confirmed α8 integrin expression in kidney mesangial cells and their sEVs. The CD9-α8 integrin double-positive sEVs were successfully detected using on-bead flow cytometry. Western blot analysis further revealed transplanted kidney-derived sEVs containing blood type B antigens in non-blood type B recipients, who had received kidneys from blood type B donors. Notably, a patient experiencing graft kidney loss exhibited diminished signals of sEVs containing donor blood type antigens.
CONCLUSION
Our findings demonstrate the potential usefulness of kidney-derived sEVs in plasma in future research for kidney diseases.
Topics: Humans; Kidney Transplantation; Extracellular Vesicles; Male; Female; Middle Aged; Adult; Case-Control Studies; Mesangial Cells; Biomarkers; ABO Blood-Group System; Tetraspanin 29; Flow Cytometry; Kidney; Endothelial Cells; Blood Group Incompatibility
PubMed: 38436899
DOI: 10.1007/s10157-024-02464-z -
Bone Marrow Transplantation Jun 2024ABO-group major incompatibility hematopoietic stem cell transplantation (HSCT) increases the risk of delayed red cell engraftment and other immunological complications....
ABO-group major incompatibility hematopoietic stem cell transplantation (HSCT) increases the risk of delayed red cell engraftment and other immunological complications. In this study, we evaluated the efficacy of pre-transplant infusion of rituximab in patients with ABO-incompatibility in improving red blood cell engraftment after HSCT, measured by time to reach transfusion independence. We performed a retrospective, single-center study including 131 consecutive patients transplanted with major or bidirectional ABO-incompatible grafts between 1st January 2013 and 31st December 2019. Fifty-one patients received an infusion of rituximab during the conditioning regimen, while 80 patients did not receive any additional preventive treatment. Time to transfusion independence was significantly reduced for patients treated with rituximab (1 month, 95% CI, 0.5-2) compared with the control group (3.2 months, 95% CI 1.5-3.2, p = 0.02). By multivariable analysis, rituximab use was associated with a faster red blood cell (RBC) engraftment (RR 1.88, 95% CI 1.17-3.03, p = 0.009), while a pre-transplant anti-donor isohemagglutinins titer >1:128 was associated with delayed transfusion independence (RR 0.61, 95% CI 0.37-0.99, p = 0.05). Although limited by the retrospective nature of the study, the results of this analysis suggest that rituximab added to conditioning regimens is feasible, safe, and able to improve post-transplant red blood cell engraftment.
Topics: Humans; Rituximab; Hematopoietic Stem Cell Transplantation; Transplantation Conditioning; ABO Blood-Group System; Male; Female; Retrospective Studies; Middle Aged; Adult; Blood Group Incompatibility; Aged
PubMed: 38402345
DOI: 10.1038/s41409-024-02247-w -
Human Immunology Mar 2024ABO blood group antigens are critical determinants of immunologic self and non-self and are ubiquitously expressed on all cellular tissues. Antibodies against non-self... (Review)
Review
ABO blood group antigens are critical determinants of immunologic self and non-self and are ubiquitously expressed on all cellular tissues. Antibodies against non-self ABO antigens are naturally present and can mediate pathologic reactions against incompatible transfused blood cells and transplanted tissues. Laboratory testing for ABO antigens and isoagglutinins is essential for safe and effective transfusion and transplantation. Testing for ABO antigens has traditionally depended on serologic testing. However, there is increasing need for evaluation of genetic analysis of ABO antigens, to enable evaluation of ABO blood group in cases where serologic testing may be ambiguous or impossible to accurately perform. The clinical need for ABO genotyping is being addressed by the development of multiple molecular diagnostic approaches. Recent data have clearly demonstrated the potential utility of ABO genotyping in solid organ transplantation, yet widespread implementation has been slow. We propose that this lag is related to practical considerations in laboratory testing, including limited regulatory guidance on the performance and reporting of these assays and the absence of widely available external proficiency testing programs for quality assurance. Here we describe approaches to ABO genotyping, current initiatives in developing ABO genotyping proficiency testing programs, and laboratory quality assurance considerations for ABO genotyping.
Topics: Humans; ABO Blood-Group System; Genotype; Blood Group Incompatibility; Transplants
PubMed: 38402098
DOI: 10.1016/j.humimm.2024.110766 -
Biomedicines Feb 2024The Rh system, including the highly immunogenic D antigen, is one of the clinically most important blood group systems in transfusion medicine. Numerous alleles of the...
The Rh system, including the highly immunogenic D antigen, is one of the clinically most important blood group systems in transfusion medicine. Numerous alleles of the gene are associated with variant RhD phenotypes. In case of Rh incompatibility, some of them can induce hemolytic transfusion reactions and hemolytic disease of the fetus and newborn. Thus, accurate blood group diagnostics are critical for safe transfusion therapy. We characterized phenotypes of four individuals revealing weakened D expression during routine pre-transfusion testing. Standard gel card matrix techniques with monoclonal and polyclonal anti-D antibodies were used for serological typing, complemented using D epitope and antigen density analysis. Genotyping employing PCR with sequence-specific primers, genomic and allele-specific Sanger sequencing and in silico protein analysis were performed. Four novel alleles associated with weak D or partial D phenotypes were identified. One of the mutations is predicted to disrupt the terminal stop codon and result in an elongated translation of the mutant D protein that phenotypically exhibits a loss of D epitopes. Furthermore, a hybrid gene formed with the homologue gene is described. The presented data enhances the understanding of the Rh system and may contribute to continued advances in blood group diagnostics.
PubMed: 38398058
DOI: 10.3390/biomedicines12020456 -
Annals of Laboratory Medicine Jul 2024Rh hemolytic disease of the fetus and newborn is a potential risk for D-negative mothers who produce anti-D during pregnancy, which can lead to morbidity and mortality... (Review)
Review
Rh hemolytic disease of the fetus and newborn is a potential risk for D-negative mothers who produce anti-D during pregnancy, which can lead to morbidity and mortality in subsequent pregnancies. To prevent this hemolytic disease, Rho(D) immune globulin (RhIG) is generally administered to D-negative mothers without anti-D at 28 weeks of gestation and shortly after delivery. However, current guidelines suggest that pregnant mothers with molecularly defined weak D types 1, 2, 3, 4.0, and 4.1 do not need RhIG as they are unlikely to produce alloanti-D when exposed to fetuses with D-positive red cells. This issue and the necessity of genotyping have been extensively discussed in Western countries, where these variants are relatively common. Recent evidence indicates that women with Asian-type DEL (c.1227G>A) also do not form alloanti-D when exposed to D-positive red cells. We report that mothers with molecularly defined Asian-type DEL, similar to those with weak D types 1, 2, 3, 4.0, and 4.1, do not require RhIG before and after delivery. Collectively, this review could pave the way for the revision of international guidelines to include the selective use of RhIG based on specific genotypes, particularly in women with the Asian-type DEL.
Topics: Pregnancy; Infant, Newborn; Humans; Female; Rh-Hr Blood-Group System; Rho(D) Immune Globulin; Rh Isoimmunization; Genotype; Erythrocytes
PubMed: 38384203
DOI: 10.3343/alm.2023.0356 -
Frontiers in Immunology 2024Living donor (LD) kidney transplantation in the setting of ABO blood group incompatibility (ABOi) has been previously reported to be associated with increased risk for...
BACKGROUND
Living donor (LD) kidney transplantation in the setting of ABO blood group incompatibility (ABOi) has been previously reported to be associated with increased risk for antibody-mediated rejection (ABMR). It is however unclear if the presence of pre-transplant donor specific antibodies (DSA) works as an additive risk factor in the setting of ABOi and if DSA positive ABOi transplants have a significantly worse long-term outcome as compared with ABO compatible (ABOc) DSA positive transplants.
METHODS
We investigated the effect of pre-transplant DSA in the ABOi and ABOc setting on the risk of antibody-mediated rejection (ABMR) and graft loss in a cohort of 952 LD kidney transplants.
RESULTS
We found a higher incidence of ABMR in ABOi transplants as compared to ABOc transplants but this did not significantly affect graft survival or overall survival which was similar in both groups. The presence of pre-transplant DSA was associated with a significantly increased risk of ABMR and graft loss both in the ABOi and ABOc setting. We could not detect an additional risk of DSA in the ABOi setting and outcomes were comparable between DSA positive ABOi and ABOc recipients. Furthermore, a combination of DSA directed at both Class I and Class II, as well as DSA with a high mean fluorescence intensity (MFI) showed the strongest relation to ABMR development and graft loss.
CONCLUSION
The presence of pre-transplant DSA was associated with a significantly worse long-term outcome in both ABOi and ABOc LD kidney transplants and our results suggests that the risk associated with pre-transplant DSA is perhaps not augmented in the ABOi setting. Our study is the first to investigate the long-term effects of DSA in the ABOi setting and argues that pre-transplant DSA risk could potentially be evaluated similarly regardless of ABO compatibility status.
Topics: Humans; Kidney Transplantation; Cohort Studies; Switzerland; Living Donors; Graft Rejection; ABO Blood-Group System; Antibodies
PubMed: 38361942
DOI: 10.3389/fimmu.2024.1355128 -
Annals of Transplantation Feb 2024BACKGROUND The use of ABO-incompatible liver transplants (ABO-ILTs) from deceased donors has become more common due to the shortage of available donor livers and...
A Retrospective Study of Long-Term Outcomes in 16 ABO-Incompatible Deceased Donor Pediatric Liver Transplants from a National Transplant Center at Helsinki University Hospital, Finland, 1987-2022.
BACKGROUND The use of ABO-incompatible liver transplants (ABO-ILTs) from deceased donors has become more common due to the shortage of available donor livers and increased transplant waiting times. This retrospective study from a national transplant center at Helsinki University Hospital, Finland, aimed to assess the long-term outcomes of ABO-incompatible deceased donor pediatric liver transplants between 1987 and 2022. MATERIAL AND METHODS Sixteen (9.5%) of the 169 pediatric liver transplantations were ABO-ILTs. The median age at transplantation was 5.0 (0.5-15.4) years. Reasons for ABO-ILTs were acute liver failure (18.75%), malignancy (12.5%), small body size and long waiting time (25%), and other reasons (43.75%). The median post-transplant follow-up time was 147 (0.72-353) months. Patient and graft survival and occurrence of surgical complications were compared to ABO-identical transplants, and anti-ABO antibody titers were analyzed. RESULTS The 1-, 3-, and 5-year patient survivals were comparable between the ABO-I and ABO-compatible groups, being 81.3%, 73.9%, and 73.9% (ABO-I) and 87.5%, 82.5%, 77.9% (ABO-compatible), respectively. Three patients with ABO-ILTs died of sepsis and multiorgan failure during the first 3 months after transplantation. The occurrence of biliary complications and early vascular thrombosis (<30 days after transplantation) did not differ significantly between recipients with an ABO-ILT vs ABO-compatible liver graft. CONCLUSIONS The findings from this study support findings from previous studies that outcomes after ABO-incompatible liver transplants in children were comparable to outcomes from ABO-identical liver transplants.
Topics: Child; Humans; Child, Preschool; Adolescent; Liver Transplantation; Retrospective Studies; Finland; Blood Group Incompatibility; ABO Blood-Group System; Hospitals; Graft Survival; Graft Rejection; Living Donors
PubMed: 38347714
DOI: 10.12659/AOT.941929 -
Ginekologia Polska Feb 2024ABO blood type was hypothesised to be related to a number of infertility processes. There is still an open debate on ABO blood group's incompatibility and infertility....
OBJECTIVES
ABO blood type was hypothesised to be related to a number of infertility processes. There is still an open debate on ABO blood group's incompatibility and infertility. It was associated with ovarian reserve in women with subfertility. There is still not enough information on the influence of blood type and the immunology of follicular fluid (FF).
MATERIAL AND METHODS
78 patients were selected, who underwent in vitro fertilization (IVF) between April 2021 and January 2022. FF samples from each individual patient were taken on the day of ovarian puncture and stored at -80°C until immunological assessment. Concentration of chosen interleukins - IL-1α, IL-2, IL-4, IL-5, IL-6, IL-8 IL-10, IL-15, IL-1β, IL-18, IFN, LIF, TNFα, GCSF and PIBF-1 were measured using commercially available ELISA kits.
RESULTS
All assessed cytokines were present in the FF of exanimated patients. The concentration was compared to the blood type ABO of all women undergoing in vitro fertilization. No statistical relevance was found between blood type ABO and the concentration of GCSF, PIBF1, LIF, IL-15, IL-5, IL-8, IL-1 alfa, IL-1 beta, INF gamma, IL-2HS, IL-4HS, IL-6HS, IL-10HS in the FF obtained during ovarian puncture (p > 0,05). There was no statistically significant correlation between blood type ABO and the quality of embryo, and the positive pregnancy test in patients undergoing IVF/ET.
CONCLUSIONS
The blood type ABO does not influence the wide cytokine profile of FF obtained during ovarian puncture in women with infertility of different origin, as well as embryo quality and pregnancy rate.
PubMed: 38334336
DOI: 10.5603/gpl.98380 -
Cureus Dec 2023We present a case of a 16-year-old adolescent female with blood group O+ who was diagnosed with cystic fibrosis (CF). The patient had to be hospitalized due to septic...
We present a case of a 16-year-old adolescent female with blood group O+ who was diagnosed with cystic fibrosis (CF). The patient had to be hospitalized due to septic shock and respiratory failure, and extracorporeal membrane oxygenation and mechanical ventilation were applied. Faced with high urgency, she was promptly enlisted for a lung transplant, ultimately receiving a blood group A1 deceased donor lung through rescue allocation. Bilateral incompatible lung transplantation, with parental consent, was successfully performed. The postoperative course was favorable, marked by the administration of rabbit anti-thymocyte globulin, plasmapheresis, and immunosuppression (mycophenolate, steroids, and tacrolimus) as per the prescribed protocol. Notably, the patient experienced a smooth recovery without infectious complications or humoral rejection. This case highlights the viability of lung transplantation in cases of ABO incompatibility, particularly for patients in urgent need on the transplant waiting list.
PubMed: 38274919
DOI: 10.7759/cureus.51116 -
Annals of Laboratory Medicine Jul 2024Neutralizing capacity measurement (NCM) of soluble ABH substances (SAS) in plasma was assessed to guide the selection of the appropriate ABO group of fresh-frozen plasma...
Neutralizing capacity measurement (NCM) of soluble ABH substances (SAS) in plasma was assessed to guide the selection of the appropriate ABO group of fresh-frozen plasma (FFP) for plasma exchange (PE) in blood group O recipients with ABO-incompatible transplantations. Neutralizing capacity was assessed by measuring anti-A and/or anti-B titers in samples comprising one unit of O FFP and 10 O EDTA plasma samples and subtracting the binary logarithm of the titer in each group with a saline dilution. Ten EDTA plasma samples with Lewis b (Le) antigen positivity and 10 sets of pooled FFP from each blood group were used as diluents. In O FFP, the NCM values (mean±SD) were 3.4±0.52 (2.6±0.52) and 2.6±0.52 (1.5±0.3) in B and AB for IgM (total antibody) anti-B (both <0.001), and in the 10 O EDTA plasma samples, they were 3.9±0.88 (3.1±0.88) and 3.2±0.79 (2.4±0.97) for IgM (=0.0013) and total anti-B (=0.025), respectively. analysis revealed that B FFP is more effective than AB FFP in reducing IgM and total anti-B antibody titers in O recipients, regardless of Le antigen positivity.
Topics: Humans; Edetic Acid; Plasma; Plasma Exchange; Blood Group Incompatibility; ABO Blood-Group System; Immunoglobulin M
PubMed: 38237929
DOI: 10.3343/alm.2023.0393