ABO Blood Group Status Research Articles

ABO and Rh blood group distribution in ANA positive patients

Aims: Antinuclear antibody (ANA) positivity is a common finding in various autoimmune diseases, particularly those of rheumatologic origin. While ANA positivity alone may not be diagnostic, it serves as a valuable marker when supported by clinical findings, aiding in the diagnosis and prediction of autoimmune diseases. The relationship between blood group systems and various diseases has been an area of interest in medical research. In this study, we aimed to investigate the potential association between ABO blood group and ANA positivity, specifically examining whether the ABO blood group status poses a risk for autoimmune diseases in individuals with rheumatologic conditions. Methods: In this retrospective study, we analyzed the blood group data of 536 patients who tested positive for ANA and were receiving treatment for rheumatologic diseases. The blood group status of these individuals was determined using standard serologic techniques. The distribution of ABO and Rh factor blood groups among ANA-positive patients was compared with the blood group distribution in the general population. Statistical analysis was performed to assess any significant differences. Results: The analysis revealed that the distribution of ABO and Rh factor blood groups among ANA-positive individuals did not show a statistically significant difference compared to the general population. Specifically, there was no significant deviation in the prevalence of ABO blood groups (A, B, AB, O) or Rh factor (positive or negative) among ANA-positive patients compared to expected frequencies based on population data. Conclusion: Based on our findings, there appears to be no significant association between ABO blood group status and ANA positivity in patients with rheumatologic diseases. The distribution of ABO and Rh blood groups among ANA-positive individuals closely resembled that of the general population. Therefore, our study suggests that current blood group status may not serve as a predictive factor for autoimmune diseases in individuals who test positive for ANA. Further research is warranted to explore other potential factors contributing to autoimmune disease susceptibility.

A Study on Blood Group Distribution, Bleeding Time, and Clotting Time Variation among First-year Undergraduate Medical Students

Abstract Background: ABO blood group status of an individual is an important test that helps in blood grouping, cross-matching, solving medicolegal aspects, etc. Furthermore, bleeding time (BT) and clotting time (CT) are important tests to plan surgery, check response to anticoagulants, etc. BT is affected by platelet function while CT is affected by clotting factors. BT is prolonged in congenital or acquired platelet abnormalities. Defect or absence of one or more factors can cause prolonged CT. Aims and Objectives: To determine the blood group, of the students and to determine their BT and CT. Materials and Methods: Institution-based cross-sectional observational study done in the Department of Physiology, Tripura Medical College and Dr. BRAM Teaching Hospital. BT and CT were done by Duke’s Method and Capillary glass tube method respectively. Blood groups were determined based on the presence or absence of agglutination. Qualitative data were expressed in percentage and quantitative data in frequency, mean, and standard deviations. Results: Sixty-one (58%) females and 44 (42%) males participated. Blood group O and blood groups B (33.3%) were equally most predominant. BT is >4 min (total) in 13% of students (n = 14) with slightly more in males (16% males). In addition, CT is >6 min in 37% of students (n = 39) with slightly more in females (39% females). Conclusion: In our study, blood group O and blood group B were equally the most predominant. CT toward upper normal ranges (>6 min) slightly more in females than males.

Plasma proteomic associations with genetics and health in the UK Biobank

The Pharma Proteomics Project is a precompetitive biopharmaceutical consortium characterizing the plasma proteomic profiles of 54,219 UK Biobank participants. Here we provide a detailed summary of this initiative, including technical and biological validations, insights into proteomic disease signatures, and prediction modelling for various demographic and health indicators. We present comprehensive protein quantitative trait locus (pQTL) mapping of 2,923 proteins that identifies 14,287 primary genetic associations, of which 81% are previously undescribed, alongside ancestry-specific pQTL mapping in non-European individuals. The study provides an updated characterization of the genetic architecture of the plasma proteome, contextualized with projected pQTL discovery rates as sample sizes and proteomic assay coverages increase over time. We offer extensive insights into trans pQTLs across multiple biological domains, highlight genetic influences on ligand–receptor interactions and pathway perturbations across a diverse collection of cytokines and complement networks, and illustrate long-range epistatic effects of ABO blood group and FUT2 secretor status on proteins with gastrointestinal tissue-enriched expression. We demonstrate the utility of these data for drug discovery by extending the genetic proxied effects of protein targets, such as PCSK9, on additional endpoints, and disentangle specific genes and proteins perturbed at loci associated with COVID-19 susceptibility. This public–private partnership provides the scientific community with an open-access proteomics resource of considerable breadth and depth to help to elucidate the biological mechanisms underlying proteo-genomic discoveries and accelerate the development of biomarkers, predictive models and therapeutics1.

Blood Group A Enhances SARS-CoV-2 Infection

BACKGROUND: Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) continues to infect millions of individuals worldwide. However, not all individuals are equally susceptible to infection. Many studies have demonstrated that the first polymorphism described in the human population, ABO(H) blood group antigens, are associated with increased risk of SARS-CoV-2 infection. While conflicting data exist, the most common findings suggest that individuals with blood group A exhibit an increased risk of infection when compared to blood group O individuals. However, the mechanism whereby ABO(H) blood group status influences SARS-CoV-2 infection has remained unknown. The receptor binding domain (RBD) of SARS-CoV-2, which facilitates host cell engagement, bears significant similarity to galectins, an ancient family of carbohydrate binding proteins previously shown to recognize ABO(H) blood group antigens. As a result, we hypothesized that SARS-CoV-2 may recognize blood group A directly through its RBD and that this may in part account for increased susceptibility of blood group A individuals for SARS-CoV-2 infection. Methods: The SARS-CoV-2 RBD from the parent strain (Wuhan-Hu-1) and variants (Delta and Omicron), in addition to individual human galectins (1, 2, 3, 4, 7 and 9) were cloned, purified and subjected to glycan binding specificity analysis using a glycan microarray populated with hundreds of distinct glycans, including blood group antigens. This was accomplished by incubating each fluorescently labeled RBD or galectin on the array, followed by detection of bound fluorescence using a microarray scanner (GenePix 4000 B, Molecular devices) and integrated spot intensity analysis using Imagene software (GenePix Pro 7). SARS-CoV-2 with distinct spike proteins (Wuhan-Hu-1, Delta, and Omicron) were used to assess infection using Chinese hamster ovary (CHO) cells engineered to express angiotensin converting enzyme 2 (ACE2) and type 1 blood group A or H (blood group O antigen). A one-way ANOVA with a Tukey's post hoc with a p value <0.05 was considered significant. Results: Sequence analysis of galectins demonstrates that several galectins possess up to 11% sequence identity with the RBDs of SARS-CoV-2 WT (Wuhan-Hu-1) and variants (Delta and Omicron). Each RBD (Wuhan, Delta and Omicron) exhibited glycan binding specificity that overlapped with distinct members of the galectin family, with the highest similarity observed toward the C terminal domain of galectin-4 (Gal-4C). Direct comparison of binding toward ABO(H) antigens demonstrated that each RBD and Gal-4C displayed high specificity for the type 1 blood group A structure uniquely found on respiratory epithelial cells when compared to other blood group antigens (p<0.0001). To specifically examine the impact of blood group A on SARS-CoV-2 infection, CHO cells were engineered to express ACE2 and the type 1 blood group A or H antigen (the antigen expressed in blood group O individuals) normally found on respiratory epithelial cells. Consistent with the increased binding of the RBD to blood group A on the glycan microarray, enhanced binding was observed by each RBD toward blood group A expressing cells (p<0.001). Blood group A cells were also significantly more likely to be infected with Wuhan-Hu-1, Delta and Omicron variants of SARS-CoV-2 when compared to blood group O cells, while pre-incubation of cells with Gal-4C specifically inhibited infection of blood group A expressing cells, while failing to impact infection of blood group O cells (p<0.001). Conclusions: These results demonstrate a direct effect of blood group A on viral infection and suggest that blood group A individuals may exhibit an increased susceptibility to SARS-CoV-2 as a result of direct engagement of the blood group A antigen. However, variations in ACE2 levels, blood group A expression and many other factors likely influence the overall risk of SARS-CoV-2 infection following exposure in a given individual. The present results provide one mechanism whereby blood group A itself may directly influence SARS-CoV-2 infectious risk.

The distribution of ABO RhD blood groups in Australia, based on blood donor and blood sample pathology data

To determine the distribution of ABO RhD blood groups in Australia in 2019. Retrospective analysis of blood group data for blood donors (Australian Red Cross Lifeblood National Blood Management System) and for people whose blood type was determined in samples submitted for analysis by hospital-based or private pathology agencies. All Australian states and territories, 1 January - 31 December 2019. Proportions of donors and patients, by ABO blood group and RhD status. These proportions were compared with published data for 1993-94 first-time blood donors. A total of 1318751 valid ABO RhD blood group results were provided by 28 of 41 invited pathology agencies (including 245 of 324 approved health providers, 76%). Valid ABO RhD data were available for 490491 blood donors, including 103798 first-time donors (21.2%). Blood group prevalence based on samples typed by pathology services was O RhD+, 38.4%; O RhD-, 6.5%; A RhD+, 32.0%; A RhD-, 5.6%; B RhD+, 11.8%; B RhD-, 1.5%; AB RhD+, 3.7%; and AB RhD-, 0.5% (totals: RhD+, 85.9%; RhD-, 14.1%). The distribution based on typing of first-time blood donors was similar. The overall proportion of RhD+ first-time donors rose from 81% in 1993-94 to 83.8% in 2019; the proportion of groups B and AB RhD+ RBC units issued declined from 9.8% in 2010-11 to 6.9% of all RBC units in 2019-20, while that of O RhD- RBC units increased from 11.7% to 17.4%. Our national assessment of ABO RhD prevalence in Australia provides updated information for re-evaluating blood and blood product collection and holdings in light of changes in population demographic characteristics.

Influence of Cancer Susceptibility Gene Mutations and ABO Blood Group of Pancreatic Cancer Probands on Concomitant Risk to First-Degree Relatives.

ABO blood group is associated with pancreatic cancer risk. Whether ABO blood group alone or when combined with inherited mutation status of index pancreatic cancer cases (probands) can enhance pancreatic cancer risk estimation in first-degree relatives (FDR) is unclear. We examined FDRs' risk for pancreatic cancer based on probands' ABO blood group and probands' cancer susceptibility gene mutation status. Data on 23,739 FDRs, identified through 3,268 pancreatic cancer probands, were analyzed. Probands' ABO blood groups were determined serologically or genetically, and 20 cancer susceptibility genes were used to classify probands as "mutation-positive" or "mutation-negative." SIRs and 95% confidence intervals (CI) were calculated, comparing observed pancreatic cancer cases in the FDRs with the number expected in SEER-21 (reference population). Overall, FDRs had 2-fold risk of pancreatic cancer (SIR = 2.00; 95% CI = 1.79-2.22). Pancreatic cancer risk was higher in FDRs of mutation-positive (SIR = 3.80; 95% CI = 2.81-5.02) than mutation-negative (SIR = 1.79; 95% CI = 1.57-2.04) probands (P < 0.001). The magnitude of risk did not differ by ABO blood group alone (SIRblood-group-O = 1.57; 95% CI = 1.20-2.03, SIRnon-O = 1.83; 95% CI = 1.53-2.17; P = 0.33). Among FDRs of probands with non-O blood group, pancreatic cancer risk was higher in FDRs of mutation-positive (SIR = 3.98; 95% CI = 2.62-5.80) than mutation-negative (SIR = 1.66; 95% CI = 1.35-2.03) probands (P < 0.001), but risk magnitudes were statistically similar when probands had blood group O (SIRmutation-positive = 2.65; 95% CI = 1.09-5.47, SIRmutation-negative = 1.48; 95% CI = 1.06-5.47; P = 0.16). There is a range of pancreatic cancer risk to FDRs according to probands' germline mutation status and ABO blood group, ranging from 1.48 for FDRs of probands with blood group O and mutation-negative to 3.98 for FDRs of probands with non-O blood group and mutation-positive. Combined ABO blood group and germline mutation status of probands can inform pancreatic cancer risk estimation in FDRs.

Association of ABO Blood Group Status in Patients with Breast Lesions and Emphasis on Invasive Breast Carcinoma

Introduction: The ABO blood group antigens are expressed on the erythrocyte membrane and on the surface of other normal and pathological cells. Recently, there has been an increasing research interest in the association between ABO blood group antigens and certain type of human cancers. Aim: To determine the association of ABO blood group and Rh blood type in patients with breast lesions. Materials and Methods: It was a retrospective observational study done at a rural tertiary care referral institute, PES Institute of Medical Sciences and Research (PESIMSR), Kuppam, Andhra Pradesh, India, from January 2015 to December 2018. Apparently healthy female voluntary blood donors constituted the control group (n=222). Patients with breast lesions constituted the study group (n=125). The association of the breast lesions with ABO blood group and Rh blood type was analysed. Frequencies, Chi‑square test and crosstabs were the statistical tools used for data analysis. All the statistical calculations were performed through Statistical Software for Data Science (STATA) version 14.1. Results: Total 125 cases of breast lesions were analysed. Neoplastic lesions 113 (90.4%) were more common than the non neoplastic lesions 12 (9.6%). Blood group “O” was the most common blood group in malignant neoplasms and was statistically significant (p=0.045). Blood group B was the most common blood group in grade II invasive breast carcinoma and was statistically just significant (p=0.05). Conclusion: A definite change in the pattern of distribution of ABO blood group was observed in grade II malignant neoplasms. It may be hypothesised that knowing the blood group of breast cancer patients may be beneficial in order to triage the patients for the purpose of efficient management.

Determination of C,c,E and e Antigens Section Prevalence in Rh D Negative Individuals: Is it Good Exercise with Utilities in Clinical Blood Transfusion Practices?

Introduction: Besides D antigen, C,c,E and e antigens of Rh blood group system are the most important antigens involved in alloimmunisation. The prevalence of C,c,E and e antigens in Rh D negative individuals in local population has many utilities in transfusion medicine practice. Aim: To determine the prevalence of C,c,E and e antigens in Rh D negative individuals. Materials and Methods: This prospective observational study was performed at Bhanumati clinical laboratory, Navsari, Gujarat, India, from January 2020 to January 2022. A total of 270 Rh D negative samples irrespective of ABO blood group status were typed for C,c,E and e antigen using monoclonal reagents from two different manufacturers using conventional tube technique. The most likely phenotype and genotype were determined using reference textbooks. Possibility of weak D in these 270 samples was ruled out using polyspecific Antihuman Globulin Reagent performing test for weak D antigens. Results were analysed using Excel spread sheet. Results: Prevalence of C,c,E, and e antigen in the 270 Rh D negative samples were, C (17, 6.29%), c (267, 98.88%), E (1, 0.37%) and e (270, 100%). Most probable genotypes were dce/ dce(rr), dCe/dce(r’r), dCe/dCe(r’r’) and dcE/dce(r’’r). Conclusion: Data obtained of C,c,E and e antigen prevalence in Rh D negative individuals is having varied utilities in blood transfusion services such as formulating rare blood group registry, preparing in house screening and panel red cells, and maintaining inventory of rare blood group units using freezing technology, if available.

Non-ABO red cell antibodies and risk of COVID-19

It is not known whether non-ABO antibodies confer any protective effect against SARS-CoV-2 infection or COVID-19 severe illness alone or in conjunction with O blood group. This cohort study included 413 576 persons in Ontario, Canada with known ABO blood group and non-ABO antibody screen status, who subsequently underwent SARS-CoV-2 viral RNA polymerase chain reaction testing between January and November 2020. The risk of SARS-CoV-2 infection or COVID-19 severe illness was not associated with the presence of non-ABO antibodies, even among persons with O blood group.

Blood group type A secretors are associated with a higher risk of COVID-19 cardiovascular disease complications.

The SARS‐CoV‐2 virus causes COVID‐19, an infection capable of causing severe disease and death but which can also be asymptomatic or oligosymptomatic. We investigated whether ABO blood group or secretor status was associated with COVID‐19 severity. We investigated secretor status because expression of ABO glycans on secreted proteins and non‐erythroid cells are controlled by a fucosyltransferase (FUT2), and inactivating FUT2 mutations result in a non‐secretor phenotype which protects against some viral infections. Data combined from healthcare records and our own laboratory tests (n = 275) of hospitalized SARS‐CoV‐2 polymerase chain reaction positive patients confirmed higher than expected numbers of blood group A individuals compared to O (RR = 1.24, CI 95% [1.05, 1.47], p = 0.0111). There was also a significant association between group A and COVID‐19‐related cardiovascular complications (RR = 2.56, CI 95% [1.43, 4.55], p = 0.0011) which is independent of gender. Molecular analysis revealed that group A non‐secretors are significantly less likely to be hospitalized than secretors. Testing of convalescent plasma donors, among whom the majority displayed COVID‐19 symptoms and only a small minority required hospitalization, group A non‐secretors were slightly over‐represented. Our findings showed that group A non‐secretors are not resistant to infection by SARS‐CoV‐2, but are more likely to experience a less severe form of associated disease.

Association between ABO blood group status and cochlear/neural function: auditory brainstem response findings

Background ABO blood group status may be a risk factor for some diseases, including hearing loss. Individuals with blood group O show a higher prevalence of hearing loss after industrial noise exposure. Group O individuals with normal hearing show reduced amplitudes in otoacoustic emission recordings. Whether blood group status affects auditory brainstem responses (ABR), which reflect cochlear hair cell and auditory nerve bioelectric activity, is unclear. Aims/objectives To compare cochlear and peripheral neural function across ABO blood groups by recording cochlear microphonic (CM) and wave I ABR responses. Material and methods Sixty normal-hearing young adults, with 15 participants from each blood group, completed 70 dB nHL click stimulus ABR measures. CM amplitude, wave I amplitude and wave I latency data were obtained for both ears. One-way ANOVA tests compared results across the ABO groups. Results A statistically significant difference for wave I peak-to-peak amplitudes across the four groups was found. Post-hoc comparisons revealed group O had significantly reduced wave I amplitudes compared to group A participants. A consistent trend of reduced CM amplitudes and prolonged wave I latencies was shown in group O participants. Conclusions and significance Emerging evidence exists that ABO blood group status may influence auditory function.

Study of ABO blood grouping and secretor status among habituals – A case control study

The study was conducted to analyse ABO blood group and secretor status using saliva among habituals and healthy controls. The relationship between ABO blood group, secretor status of habituals and oral potentially malignant disorders (OPMDs) was assessed. Salivary secretor status was studied in 100 individuals. Clinical and habit history was noted. Group I had 50 age and sex matched healthy controls; group II had 50 individuals having habit history, with or without PMD. With 1ml of unstimulated saliva from each, Wiener agglutination test was performed to know blood group and secretor status. The relationship between ABO blood groups, secretor status, and OPMDs was assessed using Chi-square test and odds ratio. Group I had blood groups A (44%), B (32%), O (14%), AB (10%) and group II had A (32%), B (26%), O (34%), AB (8%). Non-secretor status in group I was 18% and group II, 82%. In Group II, 20% nonsecretors presented with PMD, predominantly oral submucous fibrosis followed by leukoplakia and lichen planus. A definite correlation between salivary secretor status and development of PMD indicates non-secretors possess greater risk of developing oral lesions. Among the habituals, blood groups B and O were at higher risk than A and AB.

Distribution of Blood Groups in Patients with Angiographically Defined Coronary Artery Disease in Iranian Community

In the past, the relationship between coronary artery disease (CAD) and been studied extensively. The ABO blood group has a significant effect on homeostasis and is therefore associated with adverse cardiovascular events. This study aimed to determine the distribution of ABO blood group and rhesus (Rh) status (ABO/Rh) in patients with different severity of CAD in Iranian community. A total of 1,236 CAD patients undergoing angiography were evaluated and their ABO/Rh blood type was determined in a study center between February 2005 and December 2010. Of the 1,236 records, only 1,046 medical documents recorded the number of involved vessels. The patients were classified according to the number of significantly affected stenotic vessels into single vessel (1VD), two vessels (2VD), and three vessels (3VD) disease subgroups. A substantially different ABO/Rh blood groups distribution was seen in the examined samples (O: 29.7%, A: 39.7%, B: 22.2%, AB: 8.3%, Rh positivity: 89.2%). The ABO/Rh blood group phenotype distribution in CAD patients with 1VD, 2VD, and 3VD was as follows: 37.5%, 41.3%, and 41.5%, respectively, for group A; 24.1%, 20.5%, and 20.6%, respectively, for group B; 31.2%, 26.8%, and 30.2%, respectively, for group O; 7.1%, 11.4% and 7.7%, respectively, for group AB (p = 0.26), and 88.7%, 90.5%, and 87.6%, respectively, for Rh positivity, (p = 0.47). In addition, no significant correlation was not found among the ABO/Rh blood group distribution and the number of vessels involved, however, according to the different distribution of ABO/Rh blood group in CAD patients and healthy population, ABO/Rh might have an unknown role in CAD patients.&#x0D; Keywords: Coronary artery disease, Blood group, Stenosis, Vessel, Rhesus.

ABO Blood Group and the Risk of Esophageal Squamous Cell Carcinoma in Kashmir, a High Risk Region.

ABO blood group has been linked with a number of diseases including cancer. Association of ABO blood type with esophageal squamous cell carcinoma (ESCC) has been sparsely reported and the results are inconsistent. We undertook this study to analyze if any association exists between the ABO and Rh blood groups and ESCCrisk. We conducted a hospital-based case control study to analyze ABO and Rh blood groups in patients with histologically proven diagnosis of ESCC and compared them with healthy donors from the same population. ABO and Rh blood group status of general population was obtained from the blood bank at Sher-i-Kashmir Institute of Medical Sciences (SKIMS) and from original articles published from time to time. Chi-Square test was performed to look for statistical significance. For this study, 206 patients were prospectively enrolled. Seventy-four (35.9%) patients had blood group O. Blood groups type A and type B was found each in 59 (28.6%) patients. In 108,014 healthy donors, 35.3% had blood type O followed by type B (33.66%). There was no significant difference in any of the blood types between patients with ESCC and donors (P = 0.31). No association exists between ABO blood type and the risk of ESCC.

Is ABO blood group a risk or prognostic factor for patients with endometrioid endometrial cancer? A retrospective analysis in Germany.

A relationship is known to exist between gastric and pancreatic cancers and ABO antigens, caused by various immune modulations related to the ABO blood group of the patient. A similar relationship with regard to gynaecological cancers remains controversial. Patients who underwent surgery for endometrioid endometrial cancer in International Federation of Gynaecology and Obstetrics (FIGO) stage I, II, III or IV from 2006 to 2018 were identified. The research explored the existence of a relationship between the patients' blood group or Rhesus factor and the incidence of endometrial cancer, grade (G1, G2, G3), FIGO stage, nodal status, recurrence, menopausal status, parity, and body mass index. Statistical methods such as the chi-square test, analysis of variance and the Scheffé post-hoc test were used. Two hundred and two patients with endometrioid endometrial cancer were included: 96 had blood group A, 19 blood group B, 75 blood group 0, and 12 had blood group AB. This distribution corresponds to the general blood group distribution in Germany. The vast majority of the dependent variables, such as grade, FIGO stage, nodal status or recurrence were not significantly associated with ABO blood group or Rhesus factor status. The relative frequencies of G1 and G3 endometrial cancers with respect to blood group were similar. Menopausal status, parity, and body mass index were not related to more advanced FIGO stages at initial diagnosis or to ABO blood group. Blood group screening would probably not be helpful in the diagnosis of endometrioid endometrial carcinomas in early stages compared to the current gold standard. Furthermore, a specific blood group does not increase either the risk of recurrence or the risk of a dedifferentiated type of endometrial carcinoma.

Hematopoietic Cell Transplantation Donor Selection Reimagined: KIR-KIR Ligand Interactions and a Formalized Donor Risk Index Effective at Predicting Survival

When selecting a human leukocyte antigen (HLA) matched unrelated donor (URD) for hematopoietic cell transplantation (HCT) it is generally accepted that donor age, sex, ABO blood group and viral serologic status should be considered. However, the inter-relationship among these variables is not well established and a consensus on how strongly to consider each variable has not been reached. Selection of the optimal donor gets more complicated as new donor recipient pair (DRP) selection parameters, including killer immunoglobulin-like receptors (KIR) haplotypes are included. In this study we seek to develop a logic-based method to reduce the inconsistencies in donor selection in the HLA matched HCT. Retrospective review of eligible adults with known KIR genotyping receiving HLA-A, B, C & DRB1 allelically matched URD HCT for hematologic malignancy. Donor recipient pairs were selected based on donor age, sex match, CMV sero-status match, and ABO compatibility when possible; KIR genotype was not considered in DRP selection. KIR-KIR ligand interactions were calculated for each DR pair and interaction unit values were ascribed as previously described and each DRP IM KIR score (eq. 1) was calculated. IM KIR Score = |iKIR| + |mKIRL| [1] Weights of each donor risk variable (age, sex, CMV & ABO match) contribution were ascribed using Cox regression methods and summed up to determine donor risk parameter. Donor risk parameters and reciprocal-IM-KIR were finally combined into a donor risk index. Ninety-eight DRP with known HLA & KIR genotyping were studied. A higher IM-KIR score describes a DRP with increased iKIR-KIR ligand interactions and missing KIR ligand interactions; which was associated with a favorable survival after HCT, HR of 0.44 (95%CI: 0.26 to 0.73; P=0.002). Univariate analysis of overall survival for donor age, sex match, ABO compatibility and CMV status were all statistically insignificant (p>0.05). Donor risk parameter was predictive of mortality with a hazard ratio (HR) of 2.76 (95% CI: 1.22-6.18, p=0.014). Combining the two into a donor risk index was predictive of survival with a HR of 2.38 (1.44-3.92, p=0.001). ROC-AUC comparison of survival for IM-KIR score and donor risk parameter showed AUCs of 0.63 and 0.67 respectively. Further, the combined donor risk index shows improved sensitivity and specificity over the donor risk parameter with AUCs of 0.72 and 0.67 respectively. A novel IM-KIR score independently predicts survival in HLA matched DRP, as does a formalized donor risk parameter which includes non-HLA donor characteristics. Moreover, their addition enhanced the specificity and sensitivity of predicting survival in these patients. If validated in a larger exploration and validation cohort this method of donor selection may improve the donor selection process, decreasing variability in clinical outcomes and improve overall survival.

Hematopoietic Cell Transplantation Donor Selection Reimagined: KIR-KIR Ligand Interactions and a Formalized Donor Risk Index Effective at Predicting Survival

Background When selecting a human leukocyte antigen (HLA) matched unrelated donor (URD) for hematopoietic cell transplantation (HCT) it is generally accepted that donor age, sex, ABO blood group and viral serologic status should be considered. However, the inter-relationship among these variables is not well established and a consensus on how strongly to consider each variable has not been reached. Selection of the optimal donor gets more complicated as new donor recipient pair (DRP) selection parameters, including killer immunoglobulin-like receptors (KIR) haplotypes are included. In this study we seek to develop a logic-based method to reduce the inconsistencies in donor selection in the HLA matched HCT. Methods VCU IRB approval was obtained for a retrospective review of eligible subjects who were adults with known KIR genotyping receiving HLA-A, B, C &amp; DRB1 allelically matched URD HCT for hematologic malignancy between 2014 and 2017. Donor recipient pairs were selected based on donor age, sex match, CMV sero-status match, and ABO compatibility when possible; KIR genotype was not considered in DRP selection. KIR-KIR ligand interactions were calculated for each DR pair and interaction unit values were ascribed as follows; -1, when the donor possessed an inhibitory KIR (iKIR) and the recipient the corresponding HLA; +1, when the donor possessed iKIR and recipient lacked corresponding HLA (mKIR score, missing ligand). A novel inhibitory-missing KIR (IM-KIR) score was calculated for each HLA matched DRP by summing the interaction values as in equation 1. IM KIR Score = |iKIR| + |mKIRL| ………. [1] Univariate and multivariate analysis using Cox regression methods were utilized to evaluate donor parameters associated with overall survival. Weights of each donor risk variable (age, sex, CMV &amp; ABO match) contribution were ascribed and summed up to determine donor risk parameter. Donor risk parameters and reciprocal-IM-KIR were finally combined into a donor risk index. Receiver operating characteristic curve- area under the curve (ROC-AUC) analysis was utilized to compare indices. Results Ninety-eight DRP with known HLA &amp; KIR genotyping were studied. Median follow up at the time of analysis was 583 days. A higher IM-KIR score describes a DRP with increased iKIR-KIR ligand interactions and missing KIR ligand interactions; which was associated with a favorable survival after HCT, HR of 0.44 (95%CI: 0.26 to 0.73; P=0.002). Further analyses were performed using a reciprocal of this score. Univariate analysis of overall survival for donor age, sex match, ABO compatibility and CMV status were all statistically insignificant (p&gt;0.05). However, the donor risk parameter was predictive of mortality with a hazard ratio (HR) of 2.76 (95% CI: 1.22-6.18, p=0.014). Covariate analysis of the donor risk parameter and reciprocal IM-KIR score were both predictive of survival independent of each other with HR 2.41 (1.05-5.54, p=0.038) and 2.35 (1.18-4.70, p=0.016) respectively. Combining the two into a donor risk index was predictive of survival with a HR of 2.38 (1.44-3.92, p=0.001). ROC-AUC comparison of survival for IM-KIR score and donor risk parameter showed statistically significant AUCs of 0.63 and 0.67 respectively. Further, the combined donor risk index shows improved sensitivity and specificity over the donor risk parameter with AUCs of 0.72 and 0.67 respectively. Conclusions A novel KIR-HLA interaction score, the IM-KIR score independently predicts survival in HLA matched DRP, as does a formalized donor risk parameter which includes non-HLA donor characteristics. Moreover, the addition of IM-KIR score to the donor risk parameter enhanced the specificity and sensitivity of predicting survival in these patients. If validated in a larger exploration and validation cohort this method of donor selection may improve the donor selection process, decreasing variability in clinical outcomes and improve overall survival. Disclosures No relevant conflicts of interest to declare.

Genetic determinants of VWF clearance and FVIII binding modify FVIII pharmacokinetics in pediatric hemophilia A patients

Factor VIII (FVIII) pharmacokinetic (PK) properties show high interpatient variability in hemophilia A patients. Although previous studies have determined that age, body mass index, von Willebrand factor antigen (VWF:Ag) levels, and ABO blood group status can influence FVIII PK, they do not account for all observed variability. In this study, we aim to describe the genetic determinants that modify the FVIII PK profile in a population of 43 pediatric hemophilia A patients. We observed that VWF:Ag and VWF propeptide (VWFpp)/VWF:Ag, but not VWFpp, were associated with FVIII half-life. VWFpp/VWF:Ag negatively correlated with FVIII half-life in patients with non-O blood type, but no correlation was observed for type O patients, suggesting that von Willebrand factor (VWF) half-life, as modified by the ABO blood group, is a strong regulator of FVIII PK. The FVIII-binding activity of VWF positively correlated with FVIII half-life, and the rare or low-frequency nonsynonymous VWF variants p.(Arg826Lys) and p.(Arg852Glu) were identified in patients with reduced VWF:FVIIIB but not VWF:Ag. Common variants at the VWF, CLEC4M, and STAB2 loci, which have been previously associated with plasma levels of VWF and FVIII, were associated with the FVIII PK profile. Together, these studies characterize the mechanistic basis by which VWF clearance and ABO glycosylation modify FVIII PK in a pediatric population. Moreover, this study is the first to identify non-VWF and non-ABO variants that modify FVIII PK in pediatric hemophilia A patients.

Clinicopathologic İnfluence with ABO Blood Group and Rhesus Blood Group Status in Patients on Breast Cancer: A Retrospective Study

Amaç: Son zamanlarda ABO kan grubu antijenleri ile belirli tipte insan kanserleri arasındaki ilişki, özellikle pankreas ve mide kanserine yakalanma riski, araştırmaya olan ilgiyi giderek artmaktadır. Bu çalışmanın amacı, hastanemizde meme kanseri nedeniyle ameliyat yapılan 209 hastanın A, B, O ve Rh kan grupları ile meme kanseri arasındaki ilişkiyi araştırmaktır. Materyal ve Metot: 01 Ocak 2007 ile 31 Aralık 2012 tarihleri arasında Meme kanseri nedeniyle ameliyat edilen 209 hastanın dosyaları geriye dönük olarak incelendi. Hastaların yaşı, ABO ve Rh kan gurubu, ameliyat şekli ve klinik verileri hastane bilgi sistemi arşiv kayıtlarından elde edildi. Histopatolojik olarak, tümör çapı, tümör tipi, tümörün grade’i, lenf nodu metastazı varlığı, östrojen reseptörü (ER), progesteron reseptörü (PR), HER2 durumu kaydedildi. Bulgular: Hastaların ortalama yaşı 57,22 olarak bulunmuştur. Rh (+) hastalarda Rh (-) hastalara göre invaziv karsinomlar ve lenf nodu metastazı daha yüksek oranda saptanmıştır (Sırasıyla p =0,008, p =0,043). A kan grubunda östrojen reseptörü pozitifliği diğer kan gruplarına göre anlamlı olarak yüksek bulunmuştur ( p =0,049). Sonuç: A kan grubundan olan kişilerde meme kanseri daha fazla görülmekle birlikte, diğer gruplara göre A kan grubunda ER pozitifliği yüksektir. 0 kan grubunda ise ER pozitifliği düşüktür. Rh(+) hastalarda invaziv meme kanseri ve lenf nodu metastazı daha yaygındır.

Preliminary assessment of anti-α-Gal IgG and IgM levels in patients with patent Plasmodium vivax infection.

Anti-α-Gal responses may exert a protective effect in falciparum malaria. However, the biological role of such antibodies is still unknown during Plasmodium vivax infections. We investigated IgG and IgM responses to α-Gal in individuals with vivax malaria. Anti-α-Gal IgG and IgM levels were higher in these patients than in controls, but no significant correlation was found between parasitaemia and anti-α-Gal response, nor between this response and ABO blood group status. This is the first study to investigate anti-α-Gal antibodies in P. vivax-infected patients; a larger survey is necessary to achieve a better understanding of host immune response during vivax malaria.