Did you mean: alloimmunization
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Transplantation Direct Jul 2024Biomarkers that predict posttransplant alloimmunity could lead to improved long-term graft survival. Evaluation of the number of mismatched epitopes between donor and...
BACKGROUND
Biomarkers that predict posttransplant alloimmunity could lead to improved long-term graft survival. Evaluation of the number of mismatched epitopes between donor and recipient HLA proteins, termed molecular mismatch analysis, has emerged as an approach to classify transplant recipients as having high, intermediate, or low risk of graft rejection. When high-resolution genotypes are unavailable, molecular mismatch analysis requires algorithmic assignment, or imputation, of a high-resolution genotyping. Although imputation introduces inaccuracies in molecular mismatch analyses, it is unclear whether these inaccuracies would impact the clinical risk assessment for graft rejection.
METHODS
Using renal transplant patients and donors from our center, we constructed cohorts of surrogate donor-recipient pairs with high-resolution and low-resolution HLA genotyping that were racially concordant or discordant. We systemically assessed the impact of imputation on molecular mismatch analysis for cohorts of 180-200 donor-recipient pairs for each of 4 major racial groups. We also evaluated the effect of imputation for a racially diverse validation cohort of 35 real-world renal transplant pairs.
RESULTS
In the surrogate donor-recipient cohorts, imputation preserved the molecular mismatch risk category for 90.5%-99.6% of racially concordant donor-recipient pairs and 92.5%-100% of racially discordant pairs. In the validation cohort, which comprised 72% racially discordant pairs, we found that imputation preserved the molecular mismatch risk category for 97.1% of pairs.
CONCLUSIONS
Overall, these data demonstrate that imputation preserves the molecular mismatch risk assessment in the vast majority of cases and provides evidence supporting imputation in the performance of molecular mismatch analysis for clinical assessment.
PubMed: 38911277
DOI: 10.1097/TXD.0000000000001639 -
Cureus May 2024Fy3 is a high-prevalence red blood cell antigen of the Duffy (Fy) blood group system. Anti-Fy3 antibodies are rare and solely arise in individuals with a Duffy null...
Fy3 is a high-prevalence red blood cell antigen of the Duffy (Fy) blood group system. Anti-Fy3 antibodies are rare and solely arise in individuals with a Duffy null phenotype (Fy(a-b-)), which is a phenotype that mainly occurs in people of African descent. Clinically, anti-Fy3 antibodies can cause both acute and delayed hemolytic transfusion reactions in adults as well as hemolytic disease in fetuses and newborns. Here, we report the case of a 26-year-old male with sickle cell disease (SCD) and a history of anti-E alloantibodies, who was admitted to the hospital with a vaso-occlusive crisis (VOC) and associated low hemoglobin (Hb) level. For the latter he received one unit of antigen-matched and crossmatch-compatible packed red blood cells (pRBCs) without complications. Ten days later the patient was readmitted with a further VOC and associated low Hb level, again requiring a red cell transfusion. However, no crossmatch-compatible pRBCs could be identified. Laboratory testing demonstrated pan-reactivity with additional reference testing demonstrating the presence of anti-E, anti-Fy3 and anti-Jk alloantibodies. This case highlights the diagnostic and therapeutic challenges associated with blood transfusion in SCD patients with rare alloimmunization profiles.
PubMed: 38910632
DOI: 10.7759/cureus.60939 -
Medicine Jun 2024Immune thrombocytopenic purpura (ITP) comprises ~1% to 4% of thrombocytopenia cases during pregnancy. Factors predicting neonatal thrombocytopenia and associated... (Observational Study)
Observational Study
Immune thrombocytopenic purpura (ITP) comprises ~1% to 4% of thrombocytopenia cases during pregnancy. Factors predicting neonatal thrombocytopenia and associated morbidities due to maternal ITP are unclear. The present study aimed to assess the neonatal outcomes of pregnant women with ITP. Fifty-five pregnant women with ITP and their babies, born between January/2013 and April/2021, were retrospectively reviewed. Maternal and neonatal thrombocytopenia cases other than ITP were excluded from the study. Physical examination, blood count, and cranial/abdominal ultrasonography findings of the newborns were recorded. Neonatal thrombocytopenia was defined as a platelet count < 150 × 109/L. Relationship between neonatal thrombocytopenia and maternal factors was investigated. Thrombocytopenia was detected in 17/55 babies (30.9%), and 8/17 (47.1%) had symptoms of bleeding, all but one being mild bleeding. There was a significant correlation between neonatal platelet counts of < 100 × 109/L and maternal splenectomy history. Incidence of moderate and severe thrombocytopenia was higher (statistically insignificant) in neonates of mothers with ITP. No significant correlation was determined between maternal and neonatal platelet counts. There was a weak insignificant correlation between platelet counts of neonates of mothers with or without thrombocytopenia. A significant correlation was found between the presence of splenectomy before delivery in the mother and a platelet count of < 100 × 109/L in the neonate. Moderate and severe thrombocytopenia was higher in neonates of mothers diagnosed with ITP before pregnancy and needed treatment during pregnancy and/or delivery, but the difference was insignificant. Close follow-up of babies born to mothers with ITP after birth is crucial since there is no significant prediction criterion for developing neonatal thrombocytopenia and associated morbidities.
Topics: Humans; Female; Retrospective Studies; Infant, Newborn; Pregnancy; Purpura, Thrombocytopenic, Idiopathic; Cross-Sectional Studies; Adult; Platelet Count; Pregnancy Complications, Hematologic; Thrombocytopenia, Neonatal Alloimmune; Splenectomy
PubMed: 38905433
DOI: 10.1097/MD.0000000000038587 -
International Journal of Molecular... May 2024Red blood cell (RBC) transfusion, limited by patient alloimmunization, demands accurate blood group typing. The Rh system requires specific attention due to the...
Red blood cell (RBC) transfusion, limited by patient alloimmunization, demands accurate blood group typing. The Rh system requires specific attention due to the limitations of serological phenotyping methods. Although these have been compensated for by molecular biology solutions, some RhCE ambiguities remain unresolved. The mRNA length is compatible with full-length analysis and haplotype discrimination, but the mRNA analyses reported so far are based on reticulocyte isolation and molecular biology protocols that are fastidious to implement in a routine context. We aim to present the most efficient reticulocyte isolation method, combined with an RT-PCR sequencing protocol that embraces the phasing of all haplotype configurations and identification of any allele. Two protocols were tested for reticulocyte isolation based either on their size/density properties or on their specific antigenicity. We show that the reticulocyte sorting method by antigen specificity from EDTA blood samples collected up to 48 h before processing is the most efficient and that the combination of an -specific RT-PCR followed by allele-specific sequencing enables analysis of cDNA haplotypes. All samples analyzed show full concordance between phenotype and haplotype sequencing. Two samples from the immunohematology laboratory with ambiguous results were successfully analyzed and resolved, one of them displaying a novel allele (*03 c.340C>T).
Topics: Humans; Rh-Hr Blood-Group System; Haplotypes; Alleles; Reticulocytes; RNA, Messenger; Blood Transfusion; Phenotype
PubMed: 38892055
DOI: 10.3390/ijms25115868 -
Scientific Reports Jun 2024Periodontitis is a chronic inflammatory disease that affects the periodontal tissues. Although it is associated with various systemic diseases, the impact of...
Periodontitis is a chronic inflammatory disease that affects the periodontal tissues. Although it is associated with various systemic diseases, the impact of periodontitis on kidney transplantation (KT) outcomes, particularly allograft rejection, remains unclear. This study investigated the effect of periodontitis on transplant immunity, specifically examining Porphyromonas gingivalis-derived lipopolysaccharide (LPS-PG). In vitro experiments revealed that LPS-PG increased regulatory T cells (Tregs) in Lewis rat spleen cells. In a mixed lymphocyte reaction assay, concentrations of interferon-γ, indicative of alloreactivity, were lower than in controls when LPS-PG was added to the culture and when LPS-PG-administered Lewis rat spleen cells were used as responders. In a rat KT model, LPS-PG administration to recipients promoted mild tubulitis and low serum creatinine and blood urea nitrogen levels 5 days post-KT compared with PBS-administered controls. Furthermore, LPS-PG-administered recipients had an elevated Treg proportion in their peripheral blood and spleen cells, and increased infiltrating Tregs in kidney allografts, compared with controls. The elevated Treg proportion in peripheral blood and spleen cells had a significant negative correlation with serum creatinine, suggesting elevated Tregs modulated allograft rejection. These findings suggest that periodontitis might modulate alloimmune reactivity through LPS-PG and Tregs, offering insights to refine immunosuppressive strategies for KT recipients.
Topics: Animals; Lipopolysaccharides; Porphyromonas gingivalis; Kidney Transplantation; Rats; T-Lymphocytes, Regulatory; Rats, Inbred Lew; Male; Graft Rejection; Allografts; Periodontitis; Disease Models, Animal; Spleen
PubMed: 38886503
DOI: 10.1038/s41598-024-64771-5 -
Journal of Pregnancy 2024There is insufficient evidence to assess the risk of the production of clinically important alloimmune irregular red blood cell (RBC) antibodies in first-time pregnant... (Comparative Study)
Comparative Study
Comparison of the Detection Rate and Specificity of Irregular Red Blood Cell Antibodies Between First-Time Pregnant Women and Women With a History of Multiple Pregnancies Among 18,010 Chinese Women.
There is insufficient evidence to assess the risk of the production of clinically important alloimmune irregular red blood cell (RBC) antibodies in first-time pregnant women. Using the microcolumn gel antiglobulin method, 18,010 Chinese women with a history of pregnancy and pregnant women were screened for irregular RBC antibodies, and for those with positive test results, antibody specificity was determined. The detection rate and specificity of irregular RBC antibodies in women with a history of multiple pregnancies (two or more) and first-time pregnant women were determined. In addition to 25 patients who passively acquired anti-D antibodies via an intravenous anti-D immunoglobulin injection, irregular RBC antibodies were detected in 121 (0.67%) of the 18,010 women. Irregular RBC antibodies were detected in 93 (0.71%) of the 13,027 women with a history of multiple pregnancies, and antibody specificity was distributed mainly in the Rh, MNSs, Lewis, and Kidd blood group systems; irregular RBC antibodies were detected in 28 (0.56%) of the 4983 first-time pregnant women, and the antibody specificity was distributed mainly in the MNSs, Rh, and Lewis blood group systems. The difference in the percentage of patients with irregular RBC antibodies between the two groups was insignificant ( = 1.248, > 0.05). Of the 121 women with irregular RBC antibodies, nine had anti-Mur antibodies, and one had anti-Di antibodies; these antibodies are clinically important but easily missed because the antigenic profile of the reagent RBCs that are commonly used in antibody screens does not include the antigens that are recognized by these antibodies. Irregular RBC antibody detection is clinically important for both pregnant women with a history of multiple pregnancies and first-time pregnant women. Mur and Di should be included in the antigenic profile of reagent RBCs that are used for performing antibody screens in the Chinese population.
Topics: Humans; Female; Pregnancy; Erythrocytes; China; Adult; Pregnancy, Multiple; Isoantibodies; Rho(D) Immune Globulin; Sensitivity and Specificity; Antibody Specificity; MNSs Blood-Group System; Asian People; Kidd Blood-Group System; East Asian People
PubMed: 38883212
DOI: 10.1155/2024/5539776 -
Transplantation Direct Jul 2024Mesangial expansion (ME) is an understudied histologic lesion in renal allografts. The current Banff score is not reproducible and may miss important ME features. The...
BACKGROUND
Mesangial expansion (ME) is an understudied histologic lesion in renal allografts. The current Banff score is not reproducible and may miss important ME features. The study aimed to improve the quantification of ME using morphometry, assess changes over time, and determine its association with allograft loss.
METHODS
We studied ME in 1-y and 5-y surveillance biopsies in 835 kidney transplants performed between January 2000 and December 2013. ME was assessed using the Banff score by a central pathologist and by morphometry. We derived 3 different morphometric measures: (1) %ME (%glomeruli with ME in ≥2 lobules, like Banff ); (2) %ME (%glomeruli with any ME lesion); and (3) %ME area (sum of all ME areas/all glomerular tuft areas). Unadjusted and adjusted Cox models assessed the risk of death-censored allograft loss.
RESULTS
From 1- to 5-y biopsies, the mean Banff score increased from 0.18 to 0.34, whereas %ME increased from 2.5% to 13.3%. Banff score had modest correlations with morphometric ME measures. Moderate-severe %ME was present in 20.1% of 5-y biopsies, whereas only 6.6% of Banff scores were. In general, higher ME on both 1- and 5-y biopsies was associated with a deceased donor, older recipient age, recipient diabetes/obesity (present in >50% of severely affected biopsies), higher hemoglobin A1c at 5 y posttransplant, and recurrent kidney disease. Higher ME on 5-y biopsies was associated with delayed graft function. A higher Banff score at 1-y biopsy and morphometry ME measures at 5-y biopsy were associated with rejection during the first year posttransplant. Morphometric ME measures were associated with allograft loss independent of Banff scores and all clinical characteristics, including kidney function and recurrent disease. The model with %ME had the highest c-statistic (0.872).
CONCLUSIONS
Banff score underestimates the pervasiveness of ME in 5-y biopsies. ME is common and associated with alloimmune and nonalloimmune causes of graft loss.
PubMed: 38881746
DOI: 10.1097/TXD.0000000000001652 -
Food and Chemical Toxicology : An... Jun 2024Human milk lactoferrin (hmLF) is a glycoprotein with well-known effects on immune function. Helaina Inc. has used a glycoengineered yeast, Komatagaella phaffii, to...
Workshop report: A study roadmap to evaluate the safety of recombinant human lactoferrin expressed in Komagataella phaffii intended as an ingredient in conventional foods - Recommendations of a scientific expert panel.
Human milk lactoferrin (hmLF) is a glycoprotein with well-known effects on immune function. Helaina Inc. has used a glycoengineered yeast, Komatagaella phaffii, to produce recombinant human lactoferrin (Helaina rhLF, Effera™) that is structurally similar to hmLF with intended uses as a food ingredient. However, earlier FDA reviews of rhLF were withdrawn due to insufficient safety data and unanswered safety questions the experts and FDA raised about the immunogenicity/immunotoxicity risks of orally ingested rhLF. Helaina organized a panel of leading scientists to build and vet a safety study roadmap containing the studies and safety endpoints needed to address these questions. Panelists participated in a one-day virtual workshop in June 2023 and ensuing discussions through July 2023. Relevant workshop topics included physicochemical properties of LF, regulatory history of bovine LF and rhLF as food ingredients in the FDA's generally recognized as safe (GRAS) program, and synopses of publicly available studies on the immunogenicity/alloimmunization, immunotoxicology, iron homeostasis, and absorption, distribution, metabolism, and excretion of rhLF. Panelists concluded that the safety study roadmap addresses the unanswered safety questions and the intended safe use of rhLF as a food ingredient for adults and agreed on broad applications of the roadmap to assess the safety and support GRAS of other recombinant milk proteins with immunomodulatory functions.
PubMed: 38880466
DOI: 10.1016/j.fct.2024.114817 -
Cureus May 2024This review paper provides an overview of the risk factors and laboratory testing for red blood cell (RBC) alloimmunization in pregnancy. RBC alloimmunization is a... (Review)
Review
This review paper provides an overview of the risk factors and laboratory testing for red blood cell (RBC) alloimmunization in pregnancy. RBC alloimmunization is a significant medical issue that can cause haemolytic disease of the fetus and newborn (HDFN), leading to neonatal morbidity and mortality. Current HDFN prophylaxis targets only Rhesus D (RhD) alloimmunization, with no effective measures to prevent alloimmunization to other RBC antigen groups. Several factors can increase the risk of developing RBC alloimmunization during pregnancy, including fetomaternal haemorrhage, RBC and maternal genetic status, and previous transfusions. Identifying these risk factors is essential to execute the appropriate management strategies to minimize the risk of HDFN. The review also discusses the laboratory methods and overview of pregnancy management. The paper highlights the importance of identifying and managing the risk factors for RBC alloimmunization in pregnancy to minimize the risk of HDFN and improve neonatal outcomes.
PubMed: 38868295
DOI: 10.7759/cureus.60158 -
Transfusion Medicine and Hemotherapy :... Jun 2024Human leukocyte antigen (HLA)-DPB1 mismatches during hematopoietic stem cell transplantation (HSCT) with an unrelated donor result in an increased risk for the...
INTRODUCTION
Human leukocyte antigen (HLA)-DPB1 mismatches during hematopoietic stem cell transplantation (HSCT) with an unrelated donor result in an increased risk for the development of graft-versus-host disease (GvHD). The number of CD8 T-cell epitopes available for indirect allorecognition as predicted by the PIRCHE algorithm has been shown to be associated with GvHD development. As a proof of principle, PIRCHE-I predictions for HLA-DPB1 mismatches were validated in vitro and in vivo.
METHODS
PIRCHE-I analysis was performed to identify HLA-DPB1-derived peptides that could theoretically bind to HLA-A*02:01. PIRCHE-I predictions for HLA-DPB1 mismatches were validated in vitro by investigating binding affinities of HLA-DPB1-derived peptides to the HLA-A*02:01 in a competition-based binding assay. To investigate the capacity of HLA-DPB1-derived peptides to elicit a T-cell response in vivo, mice were immunized with these peptides. T-cell alloreactivity was subsequently evaluated using an interferon-gamma ELISpot assay.
RESULTS
The PIRCHE-I algorithm identified five HLA-DPB1-derived peptides (RMCRHNYEL, YIYNREEFV, YIYNREELV, YIYNREEYA, and YIYNRQEYA) to be presented by HLA-A*02:01. Binding of these peptides to HLA-A*02:01 was confirmed in a competition-based peptide binding assay, all showing an IC value of 21 μm or lower. The peptides elicited an interferon-gamma response in vivo.
CONCLUSION
Our results indicate that the PIRCHE-I algorithm can identify potential immunogenic HLA-DPB1-derived peptides present in recipients of an HLA-DPB1-mismatched donor. These combined in vitro and in vivo observations strengthen the validity of the PIRCHE-I algorithm to identify HLA-DPB1 mismatch-related GvHD development upon HSCT.
PubMed: 38867810
DOI: 10.1159/000537789