Frequency of Duffy, Kidd, Lewis, and Rh Blood Group Antigens and Phenotypes Among Donors in the Al-Ahsa Region, Saudi Arabia.

BACKGROUND: In Al-Ahsa, Saudi Arabia, the high consanguinity rates contribute to the prevalence of inherited hemoglobinopathies such as sickle cell disease and thalassemia, which frequently require blood transfusions. These transfusions carry the risk of alloimmunization, necessitating a precise blood component matching to mitigate health risks. Local antigen frequency data is vital for optimizing transfusion practices and enhancing the safety of these medical procedures for the Al-Ahsa population. METHODS: This study investigated the distribution of Duffy, Kidd, Lewis, and Rh blood group antigens in 1,549 individuals from the region; comparing the frequencies with global data. RESULTS: Serological analyses revealed a high prevalence of the Fy(a+b-) and Jk(a+b+) phenotypes in the Duffy and Kidd blood groups, respectively, with Jk(a-b-) being notably scarce. The Lewis blood group exhibited a significant presence of Le(a-b+) and Le(a+b-) phenotypes, whereas Le(a+b+) was less common. In the Rh system, the D antigen was most prevalent, with other antigens following in descending order of frequency. CONCLUSIONS: The study underscores the regional variation in antigen frequencies, emphasizing the need for local blood banks to adapt their screening and matching practices to mitigate the risk of alloimmunization and enhance transfusion safety. These findings are pivotal for refining transfusion strategies and understanding the immunohematology landscape in Al-Ahsa.

An update to Kidd blood group system.

Since publication of the original Immunohematology review of the Kidd blood group system in 2015 (Hamilton JR. Kidd blood group system: a review. Immunohematology 2015;31:29-34), knowledge has mushroomed pertaining to gene structure, alleles causing variant and null phenotypes, clinical significance in renal transplant and hemolytic disease of the fetus and newborn, and physiologic functions of urea transporters in non-renal tissues. This review will detail much of this new information.

Jk3 alloantibodies during pregnancy-blood bank management and hemolytic disease of the fetus and newborn risk.

BACKGROUND: The Kidd-null phenotype, Jk(a-b-), occurs in individuals who do not express the JK glycoprotein. Jk(a-b-) individuals can make an antibody against the Jk3 antigen, a high-incidence antigen present in more than 99.9% of most populations. This presents many challenges to the blood bank including identification of the antibody, masking of other antibodies, and how to provide transfusion support given the rarity of Jk3-negative blood products. Kidd antibodies may cause acute and delayed hemolytic reactions as well as hemolytic disease of the fetus and newborn (HDFN). In this article, we present a series of four practical cases of pregnant women with the anti-Jk3 alloantibody that demonstrate a range of clinical presentations of Kidd-related HDFN. STUDY DESIGN AND METHODS: We retrospectively reviewed the clinical and blood bank records for four patients and their newborns encountered at institutions in Tennessee, Missouri, Hawaii, and Guam with an anti-Jk3 identified during pregnancy. RESULTS: Two cases showed no significant evidence for HDFN, while two cases were of mild-to-moderate severity requiring early delivery due to elevated middle cerebral artery (MCA) flow velocities but requiring only phototherapy for hyperbilirubinemia. No intrauterine or neonatal transfusions were necessary. Anti-Jk3 alloantibody titers ranged from 2 to 128. CONCLUSION: Clinical manifestations of anti-Jk3 HDFN are generally mild to moderate. Anti-Jk3 titers were not found to correlate directly with HDFN severity. We suggest a titer of 16 to 32 as a cutoff for implementing enhanced monitoring of fetal MCA flow velocities, as such titers may be indicative of elevated HDFN risk.

High immunogenicity of red blood cell antigens restricted to the population of African descent in a cohort of sickle cell disease patients.

BACKGROUND: Sickle cell disease (SCD) patients undergo multiple red blood cell (RBC) transfusions and are regularly exposed to low-prevalence (LP) antigens specific to individuals of African descent. This study evaluated the prevalence of antibodies against LP antigens in SCD patients and the need to identify these antibodies in everyday practice. STUDY DESIGN AND METHODS: Plasma from 211 SCD patients was tested with RBCs expressing the following LP antigens: RH10 (V), RH20 (VS), RH23 (DW ), RH30 (Goa ), KEL6 (Jsa ), and MNS6 (He). RESULTS: Nine LP antibodies were found in eight patients (3.8%): five anti-RH23, two anti-RH30, and two anti-MNS6. The exposure risk, calculated for each LP antigen, was below 3% per RBC unit, for all antigens tested. Thus, in this cohort of transfused SCD patients, the prevalence of LP antibodies was similar to that of antibodies against antigens of the FY, JK, and MNS blood group systems. These findings also reveal the occurrence of anti-RH23 in SCD patients. No anti-RH20 or anti-KEL6 were found, despite the high frequency of mismatch situations. CONCLUSION: These results highlight the immunogenicity of these LP antigens, and the evanescence of antibodies against LP antigens. They also highlight the importance of appropriate pretransfusion testing for patients frequently transfused, who are likely to be exposed to multiple types of blood group antigens.

Anti-Jka that are detected by solid-phase red blood cell adherence but missed by gel testing can cause hemolytic transfusion reactions.

BACKGROUND: Kidd blood group antibodies are notorious for transient detection and hemolytic transfusion reactions. This report compares the rate of detection of anti-Jka when using gel column agglutination versus solid-phase red blood cell adherence (SPRCA) testing and documents the occurrence of hemolytic transfusion reactions in 17 recently transfused patients who developed anti-Jka that were detectable by SPRCA but were undetectable by gel. STUDY DESIGN AND METHODS: Before April 20, 2011, the laboratory used gel column agglutination as the primary method for antibody screening and identification. From April 20, 2011, to August 12, 2013, SPRCA was adopted as the primary method for antibody screen with gel remaining the primary method for identification. SPRCA identification was also performed if sufficient sample was available. Medical records were reviewed for evidence of hemolytic reaction in patients whose anti-Jka was negative or inconclusive by gel, but clearly identifiable by SPRCA at the time the anti-Jka was first identified. RESULTS: A total of 105 patients were discovered with anti-Jka from 88,478 SPRCA screens performed. In 32 patients, anti-Jka was initially discovered by SPRCA testing and concurrent gel testing was completely negative (n = 26) or inconclusive (n = 6). Seventeen of the 32 patients were recently transfused and of these six met criteria for delayed hemolytic transfusion reaction (DHTR), three had possible DHTRs, and eight had delayed serologic reactions; 13 of the transfused patients received Jk(a-) RBCs to avoid potential hemolysis. CONCLUSION: SPRCA testing significantly increased the discovery of clinically significant anti-Jka and facilitated the earlier use of Jk(a-) RBCs to avoid hemolytic transfusion reactions.

Extended matched intrauterine transfusions reduce maternal Duffy, Kidd, and S antibody formation.

BACKGROUND: Severe alloimmune hemolytic disease of the fetus is treated with intrauterine transfusions (IUTs). Despite C, c, E, e, and K matching between mother and donor, IUT results in new antibodies in approximately 25% of women. Newly formed Fy(a), Fy(b), Jk(a), Jk(b), and S antibodies are in 83% presumably induced by the IUT donor. Therefore, we intentionally extended matching between mother and IUT donor for these additional antigens. The results, after almost 8 years of applying this protocol, are reported. STUDY DESIGN AND METHODS: Data from February 2007 to August 2014 on IUT patients were retrieved from the Leiden University Medical Center database and from donors from the Sanquin National Donor Database. Maternal data included red blood cell (RBC) antigen profiles, RBC antibodies, and date and consecutive number of each IUT. From the fathers, children, and IUT donors the RBC antigen profiles were retrieved. RESULTS: A total of 182 fetuses from 159 women were treated with 481 IUTs. Of these, 317 IUTs (66%) were matched for Duffy, Kidd, and S antigens. Only matched IUTs were received by 77 women (48%) and 82 (52%) received (partly) nonmatched IUTs. Evaluable for new antibodies were 142 women. Duffy, Kidd, or S antibodies were formed by three of 69 women (4.3%) after matched IUTs and by eight of 73 women (11.0%) after nonmatched IUTs. CONCLUSION: Extended matching for all IUTs was not possible for approximately 50% of women. Strict adherence to Duffy, Kidd, and S antigens-matched IUTs decreased immunization against these antigens by 60% compared to nonmatched IUTs.

Kidd blood group system: a review.

The Kidd blood group system has been recognized as clinically important in red blood cell (RBC) serology since its identification in 1951. Forty years later, the JK glycoprotein was determined to be a product of SCL14A1 and was identical to the urea transport protein UT-B produced by HUT11A. The functional role of the protein as a urea transporter in RBC and kidney has been well documented. The polymorphism responsible for the antithetical anigens Jk(a) and Jk(b) was identified in 1994 as c.838G>A (p.Asp280Asn). Recent discoveries have expanded the system to include 23 variant alleles recognized by the International Society of Blood Transfusion that silence the protein expression and 7 variant alleles presumably producting weak or partia JK antigens. Null phenotypes have been identified in individuals of several populations including those of African, Indian, and Chinese decent, in addition to the well-documented findings in the Polynesian and Finnish populations. This review will examine the historical information about the anigens and antibodies of the JK system as well as catalog the variations of the JK gene.

Anti-Jk3 in a Filipino man.

A 62-year-old Filipino man with a history of chronic obstructive pulmonary disease, hypertension, and hyperlipidemia was admitted to the emergency department at Hospital A with recurrent fevers, weakness, and jaundice. The patient was evaluated and eventually discharged with a diagnosis of possible drug-induced hepatitis. One month later, the patient was admitted to Hospital B for recurrent fevers and weakness. The patient's hemoglobin was 3.8 g/dL. Six units of packed red blood cells (RBCs) were ordered for transfusion. The patient's sample typed as group B, D+, and the antibody screen was negative. All six units of packed RBCs appeared compatible (at immediate spin) and were transfused to the patient. His hemoglobin level 4 days post-transfusion was 9.3 g/dL, and the patient was discharged. The patient returned after a week for follow-up and his hemoglobin was found to have dropped to 8.5 g/dL, which continued to fall until it reached 7.0 g/dL. Additional packed RBCs were ordered for transfusion. during subsequent pre-transfusion compatibility testing, the antibody screen was found to be positive (all screening cells reactive at the antihuman globulin phase). An antibody identification panel was performed.The patient's serum was found to react with all panel cells tested, including the autocontrol tube. A direct antiglobulin test revealed the presence of both anti-IgG and anti-C3 coating the patient's RBCs. The specimen was then sent to a reference laboratory for further testing. Results from the reference lab testing revealed the presence of anti-Jk3 in the patient's serum. the patient was placed on steroids, and his reticulocyte count increased with no further signs of extravascular hemolysis. No additional transfusions were necessary. he was eventually discharged with a hemoglobin of 13.6 g/dL. the purpose of this case study is to report the findings of an extremely rare but clinically significant antibody, anti-Jk3.

Production of human monoclonal anti-Jk3, recognising an epitope including the Jk(a) /Jk(b) polymorphic site of the Kidd glycoprotein.

BACKGROUND AND OBJECTIVES: The Kidd blood group system consists of polymorphic antigens, Jk(a) (JK1) and Jk(b) (JK2), and a high-incidence antigen, Jk3. Anti-Jk3 is often observed in immunised Jk(a-b-) individuals. In this study, we aimed to establish a human hybridoma cell line secreting monoclonal anti-Jk3 (HIRO-294). MATERIALS AND METHODS: Peripheral blood lymphocytes of a Filipino woman with the Jk(a-b-) phenotype having anti-Jk3 were transformed with Epstein-Barr virus and then hybridised with the myeloma cell line JMS-3 using the polyethylene glycol (PEG) method. The reactivity and specificity of the anti-Jk3 were examined by serology and flow cytometry. RESULTS: Four hybridoma clones secreting anti-Jk3 were established and the antibody from one of these clones, HIRO-294, was examined. The reactivity of HIRO-294 was positive with 227 Jk(a+b-) red blood cells (RBCs), 298 Jk(a-b+) RBCs, and 1043 Jk(a+b+) RBCs, but was negative with 21 Jk(a-b-) RBCs. Eluates from Jk(a+b-) RBCs and Jk(a-b+) RBCs sensitised with the anti-Jk3 were cross-reacted with Jk(a-b+) RBCs and Jk(a+b-) RBCs, respectively. The reactivity of HIRO-294 was enhanced by the treatment of RBCs with ficin, trypsin, pronase and α-chymotrypsin, but was not changed by their treatment with neuraminidase, dithiothreitol and ethylenediaminetetraacetic acid (EDTA) glycine acid (GA). The RBCs sensitised by the anti-Jk3 were not agglutinated with the commercial reagents of anti-Jk(a) and anti-Jk(b) by saline test, whereas the nonsensitised RBCs or those sensitised by monoclonal anti-D [HIRO-3, immunoglobulin G (IgG) class] were agglutinated with those reagents. CONCLUSIONS: We established a human hybridoma cell line secreting monoclonal anti-Jk3 (HIRO-294). This antibody had unique specificity, recognising the Kidd glycoprotein including the Jk(a) /Jk(b) polymorphic site.

Notorious anti-Jk3 in a pregnant woman.

This is a case study of a 23-year-old pregnant Polynesian woman with anti-Jk3 identified in her plasma during her third visit to a hospital. This patient, with a history of mild anemia due to beta-thalassemia minor and two known transfusion of packed red cells came to an emergency room complaining of severe abdominal cramps. Her hemoglobin during her second hospital visit was 7.5 g/dL and her antibody screen was negative. Two units of crossmatch compatible packed cells were transfused with no adverse reaction and she was discharged. Four days post transfusion, she returned to the hospital complaining of back pain and fatigue and she was running a fever (101 degrees F). Her antibody screen was positive, direct antiglobulin testing was also positive and the eluate showed pan-agglutination with a red cell panel. Anti-Jk3 was identified in her plasma by the Red Cross and a delayed transfusion reaction was suspected. As a result, Kidd null crossmatch compatible units were obtained from relatives. The patient was successfully transfused and was discharged with a hemoglobin of 10.1 g/dL. The fetus appeared to be unaffected by the antibody. This case reiterates the hard-to-identify characteristics of Kidd antibodies and highlights the need for medical laboratory personnel to be informed on the prevalence of the Kidd null phenotype among various populations. Educating ethnic populations with rare phenotypes and organizing targeted blood drives may increase inventories of these rare blood phenotypes.

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.

Background: 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. Methods: 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. Results: 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 (χ 2 = 1.248, P > 0.05). Of the 121 women with irregular RBC antibodies, nine had anti-Mur antibodies, and one had anti-Dia 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. Conclusion: Irregular RBC antibody detection is clinically important for both pregnant women with a history of multiple pregnancies and first-time pregnant women. Mur and Dia should be included in the antigenic profile of reagent RBCs that are used for performing antibody screens in the Chinese population.

Tracking donor RBC survival in premature infants: agreement of multiple populations of biotin-labeled RBCs with Kidd antigen-mismatched RBCs.

BACKGROUND: Anemia, a common condition among critically ill premature infants, is affected by red blood cell (RBC) survival (RCS). We hypothesized that transfused allogeneic Kidd antigen-mismatched RBCs would demonstrate the same concurrent RCS tracking as RBCs multilabeled at separate, discrete low densities with biotin (BioRBCs). METHODS: Allogeneic RBCs from adult donors were labeled at four biotin densities, mixed, and transfused into 17 anemic premature infants. Nine of the donors and neonates were Kidd antigen mismatched. Serial posttransfusion blood samples were assayed for up to 8 wk by flow cytometry to track the survival of the proportions of Kidd antigen-mismatched and Kidd antigen-biotinylated RBCs. RESULTS: Using linear mixed modeling to compare results, RCS of the three lowest BioRBC densities was similar to RCS by Kidd antigen mismatch and to one another. RCS of RBCs labeled at the highest BioRBC density was shortened. CONCLUSION: RCS of different populations of RBCs can be tracked concurrently and reliably using the three lowest BioRBC densities. Although comparable RCS results can be achieved using Kidd antigen mismatches, BioRBCs are preferred for investigating neonatal anemia because biotin labeling of both allogeneic and autologous RBCs is possible.

Implications of the Kidd blood group system in renal transplantation.

The association of the Kidd blood group system with hemolytic transfusion reactions and hemolytic disease of the newborn is well known. The Kidd antigens, which are localized to the HUT/UT-B urea transport protein, are found on red blood cells and the endothelial cells of the blood vessels of the medulla of the kidney. Recently it has been suggested that these antigens might play a role as minor histocompatibility antigens in renal transplantation. In the current case, the appearance of an anti-Jk(b) 10 years after renal transplantation associated with early renal allograft rejection further supports the potential importance of these antigens in renal transplantation and allograft rejection.

Hemolytic disease of newborn due to anti-Jk b in a woman with high risk pregnancy.

This case illustrates the importance of blood group antibodies in antenatal serology other than Rh system as a cause of hemolytic disease of newborn (HDN). In India, antenatal antibody screening is done at majority of transfusion centers in only Rh (D) negative mothers. In this multigravida woman with high risk obstetrical history, an antenatal antibody screening by indirect antiglobulin test (IAT) was not performed as she was Rh (D) positive. Postnatal work up for the pathological jaundice in the neonate revealed that red cell alloimmunization had occurred due to anti-Jk(b). We conclude that antenatal antibody screening should be done in all pregnant women irrespective of the D antigen status to detect and manage red cell alloimmunization to any other clinically significant blood group antigens.

The manual Polybrene test has limited sensitivities for detecting the Kidd blood group system.

BACKGROUND AND OBJECTIVES: The Kidd system antibodies, if undetected, can cause immediate or delayed hemolytic transfusion reactions as well as hemolytic disease of the newborn. There have been anecdotal reports about the inefficiency of the manual Polybrene test in detecting these antibodies. Here, we sought to determine the sensitivity of the manual Polybrene test in detecting anti-Jk(a) and anti-Jk(b) antibodies and Jk(a) and Jk(b) antigens. MATERIALS AND METHODS: Ten archived anti-Jk(a)/Jk(b) antibody positive human sera were examined by both the manual Polybrene test and the indirect antiglobulin test using polyspecific antibodies, monospecific anti-IgG antibodies and anti-C3 antibodies. Furthermore, 40 randomly selected donor blood samples were collected and phenotyped for the frequencies of Jk(a) and Jk(b) antigens using the manual Polybrene test and the indirect antiglobulin test. The results from these tests were further confirmed by saline tube tests. RESULTS: The manual Polybrene test displayed an overall sensitivity of 60% in detecting anti-Jk(a) and anti-Jk(b) antibody. Specifically, it had a sensitivity of 57.14% for anti-Jk(a) antibody and a sensitivity of 66.7% for anti-Jk(b) antibody. Furthermore, the manual Polybrene test exhibited a sensitivity of 46.15% for Jk(a) antigen and a sensitivity of 77.42% for Jk(b) antigen. CONCLUSION: The manual Polybrene test has a very low sensitivity in detecting anti-Jk(a) and anti-Jk(b) antibody, especially anti-Jk(a) antibody. It is also a very insensitive test for detecting Jk(a) antigen.

Fetal hydrops and other variables associated with the fetal hematocrit decrease after the first intrauterine transfusion for red cell alloimmunization.

OBJECTIVE: To evaluate the influence of fetal hydrops and other variables on fetal hematocrit (Hct) decrease after the first intrauterine transfusion (IUT) in alloimmunized pregnancies. METHODS: From 1996 to 2006, the data of all alloimmunized pregnancies submitted to IUT were assessed. Exclusion criteria included: fetuses submitted to intraperitoneal transfusion; pregnancies complicated by other fetal abnormalities; pregnancies submitted to only one IUT, and cases in which posttransfusion or pretransfusion blood samples were not obtained. Linear regression models were implemented to assess the relationship between the rate of Hct fall after the first IUT and the following variables: fetal hydrops; antibody titer; gestational age at the first IUT; number of days between the first and second IUT; pretransfusion and posttransfusion fetal Hct values. RESULTS: Fifty fetuses fulfilled the study criteria. The fetal Hct decrease after the first IUT was 1.21 (range 0.18-2.3) %/day. The variables independently associated with the fetal Hct drop after the first IUT were the fetal hydrops (p = 0.000), the pretransfusion fetal Hct (p = 0.001) and the posttransfusion fetal Hct (p = 0.016). CONCLUSION: Fetal hydrops, pretransfusion fetal Hct and posttransfusion fetal Hct seem to influence the fetal Hct decrease between the first and second IUT. These findings may be helpful for estimating the rate of fetal Hct drop and programming the following IUT.