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The Kidd blood group system is a collection of 3 glycoprotein antigens on the surface of red blood cells (RBCs) and the vasa recta of the kidneys. These antigens are absent on other cell surfaces and tissues. The glycoprotein has the physiological function of transporting urea across membranes.[1][2] In 1951, Allen et al discovered the Kidd blood group system in a pregnant woman whose baby died of erythroblastosis fetalis. This unknown antibody was termed anti-Jka in the memory of John Kidd. Two other antigens, Jkb and Jk3, were also discovered later on. The Kidd null phenotype Jk(a−b−) was found in 1959 in a Filipino woman who developed jaundice with a blood transfusion.[3] The antigens of the Kidd blood group system are multipass transmembrane proteins, and they span the RBC membrane 10 times. These antigens are characterized by having their amino (−NH2) terminal and carboxyl (−COOH) terminal located intracytoplasmic.[4] In 1994, B Olives et al isolated a complementary DNA HUT11 from human bone marrow encoding a urea transporter, which was 80% similar to urea transporter UT3 in rats.[5] Genetics The solute carrier family 14 member 1 (SLC14A1) gene is located on the long arm of chromosome 18 (18q12.3), which encodes for the Kidd blood group antigens in human erythrocytes. The SLC14A1 gene symbolized as HUT11 or JK encodes a membrane glycoprotein that functions as a urea transporter expressed on the erythrocytes. This gene has 28,340 nucleotide base pairs and 13 exons encoding the mature protein for Kidd antigen. The Jka and Jkb antigens differ by a single amino acid due to a single nucleotide polymorphism on the fourth extracellular loop of the Kidd glycoprotein at change sequence of single amino acid variation as Asp280 (aspartic acid in Jka) and Asn280 (asparagine in Jkb). This transition mutation replaces an adenine (A) with a guanine (G) nucleotide, resulting in the Asp280Asn substitution.[6] Kidd Blood Group Antigens International Society of Blood Transfusion (ISBT) symbol for Kidd blood group system: JK International Society of Blood Transfusion (ISBT) number for Kidd blood group system: 009

The solute carrier family 14 member 1 (SLC14A1) gene is located on the long arm of chromosome 18 (18q12.3), which encodes for the Kidd blood group antigens in human erythrocytes. The SLC14A1 gene symbolized as HUT11 or JK encodes a membrane glycoprotein that functions as a urea transporter expressed on the erythrocytes. This gene has 28,340 nucleotide base pairs and 13 exons encoding the mature protein for Kidd antigen. The Jka and Jkb antigens differ by a single amino acid due to a single nucleotide polymorphism on the fourth extracellular loop of the Kidd glycoprotein at change sequence of single amino acid variation as Asp280 (aspartic acid in Jka) and Asn280 (asparagine in Jkb). This transition mutation replaces an adenine (A) with a guanine (G) nucleotide, resulting in the Asp280Asn substitution.[6] Kidd Blood Group Antigens International Society of Blood Transfusion (ISBT) symbol for Kidd blood group system: JK International Society of Blood Transfusion (ISBT) number for Kidd blood group system: 009 The Kidd blood group system consists of three antigens present on RBCs—Jka, Jkb, and Jk3. These antigens are not found on granulocytes, lymphocytes, monocytes, and platelets. Similar to other Kidd antigens, Kidd antigens are resistant to ficin, papain, trypsin, chymotrypsin, and pronase. Furthermore, the reactivity of Kidd antibodies is enhanced by these proteolytic enzymes during testing.[7][8][9] Jka antigen: ISBT symbol: Jk1 ISBT number: 009.001 Antithetical antigen: Jkb (Jk2) Cord blood RBCs: Expressed on the fetal RBCs as early as 11 weeks of gestation. Jkb antigen: ISBT symbol: Jk2 ISBT number: 009.002 Antithetical antigen: Jka (Jk1) Cord blood RBCs: Expressed on the fetal RBCs as early as 11 weeks of gestation. Jk3 antigen: ISBT symbol: Jk3 ISBT number: 009.003 High-prevalence antigen, with a frequency of nearly 100% in all populations (>99% in Polynesians) Cord blood RBCs: Jk3 is expressed on erythroblasts at a late stage of erythropoiesis Kidd Phenotypes

Antithetical antigen: Jka (Jk1) Cord blood RBCs: Expressed on the fetal RBCs as early as 11 weeks of gestation. Jk3 antigen: ISBT symbol: Jk3 ISBT number: 009.003 High-prevalence antigen, with a frequency of nearly 100% in all populations (>99% in Polynesians) Cord blood RBCs: Jk3 is expressed on erythroblasts at a late stage of erythropoiesis Kidd Phenotypes The major Kidd phenotypes are Jk(a+b−), Jk(a−b+), Jk(a+b+), and Jk(a−b−). The Jk(a−b−) phenotype or Kidd null phenotype is rare and lacks all Jka, Jkb, and Jk3 antigens. As Jk3 is a high-prevalence antigen, individuals who developed anti-Jk3 antibodies require blood transfusions from donors with the rare null phenotype. Kidd null phenotype is most abundant among Polynesians. A screening method for identifying individuals with the Kidd null phenotype involves delayed lysis of their RBCs in a 2M urea solution. These individuals show no clinical abnormality, but their capability of concentrating urine is reduced by one-third.[10][11] Table Table. Major antigenic frequencies of the Kidd phenotypes. Table reference: [12] Etiology and Epidemiology Antibodies against Kidd antigens can lead to acute and delayed hemolytic transfusion reactions. These antibodies are often involved in delayed hemolytic transfusion reactions as their level becomes undetectable with time and then rapidly increases upon re-exposure to Kidd antigens. The incidence of clinically significant red cell hemolysis due to Kidd antibodies is relatively rare but notable. These antibodies can trigger the complement system and can lead to intravascular hemolysis. The incidence of delayed hemolytic transfusion reactions is estimated from 1 in 1000 to 1 in 10,000 transfusion episodes.[13] Lab Methods for Kidd Blood Group Determination

Antibodies against Kidd antigens can lead to acute and delayed hemolytic transfusion reactions. These antibodies are often involved in delayed hemolytic transfusion reactions as their level becomes undetectable with time and then rapidly increases upon re-exposure to Kidd antigens. The incidence of clinically significant red cell hemolysis due to Kidd antibodies is relatively rare but notable. These antibodies can trigger the complement system and can lead to intravascular hemolysis. The incidence of delayed hemolytic transfusion reactions is estimated from 1 in 1000 to 1 in 10,000 transfusion episodes.[13] Lab Methods for Kidd Blood Group Determination Kidd blood group antigens can be determined using various methodologies, broadly categorized into serological and molecular techniques. The urea hemolysis test is a traditional method that assesses the ability of RBCs to withstand osmotic stress in urea. The presence of Kidd antigens allows RBCs to lyse in urea, whereas those lacking these antigens remain intact. Although this test is straightforward, it may not always provide conclusive results for all phenotypes, particularly in partial or weak expression cases.[14] Direct and indirect antiglobulin tests are also used to detect specific antibodies against Kidd antigens in serum or plasma. The direct test checks for antibodies bound to the RBCs, whereas the indirect test assesses free antibodies in the serum. These methods are essential for confirming the presence of anti-Jk antibodies, especially in patients with a history of transfusions, as they help identify any unexpected antibodies that could lead to transfusion reactions.[15]

Kidd blood group antigens can be determined using various methodologies, broadly categorized into serological and molecular techniques. The urea hemolysis test is a traditional method that assesses the ability of RBCs to withstand osmotic stress in urea. The presence of Kidd antigens allows RBCs to lyse in urea, whereas those lacking these antigens remain intact. Although this test is straightforward, it may not always provide conclusive results for all phenotypes, particularly in partial or weak expression cases.[14] Direct and indirect antiglobulin tests are also used to detect specific antibodies against Kidd antigens in serum or plasma. The direct test checks for antibodies bound to the RBCs, whereas the indirect test assesses free antibodies in the serum. These methods are essential for confirming the presence of anti-Jk antibodies, especially in patients with a history of transfusions, as they help identify any unexpected antibodies that could lead to transfusion reactions.[15] Polymerase chain reaction (PCR) is a highly sensitive molecular technique used to amplify specific DNA sequences associated with Kidd antigens. This method can identify genotypes corresponding to various Kidd phenotypes, making it particularly useful when serological methods yield inconclusive results. In addition, PCR can help predict the likelihood of hemolytic disease in the newborn (HDN) by determining maternal antibody status.[16] PCR-SSP (sequence-specific primers) employs primers that specifically bind to known sequences within the Kidd gene, allowing for accurate determination of Kidd phenotypes. This method is cost-effective and suitable for routine testing, especially in blood banks.[17][18] PCR-RFLP (restriction fragment length polymorphism) uses restriction enzymes to cut DNA at specific sites, enabling analysis of variations in the Kidd gene. This technique provides detailed information about genetic polymorphisms associated with different Kidd phenotypes.[19]

Polymerase chain reaction (PCR) is a highly sensitive molecular technique used to amplify specific DNA sequences associated with Kidd antigens. This method can identify genotypes corresponding to various Kidd phenotypes, making it particularly useful when serological methods yield inconclusive results. In addition, PCR can help predict the likelihood of hemolytic disease in the newborn (HDN) by determining maternal antibody status.[16] PCR-SSP (sequence-specific primers) employs primers that specifically bind to known sequences within the Kidd gene, allowing for accurate determination of Kidd phenotypes. This method is cost-effective and suitable for routine testing, especially in blood banks.[17][18] PCR-RFLP (restriction fragment length polymorphism) uses restriction enzymes to cut DNA at specific sites, enabling analysis of variations in the Kidd gene. This technique provides detailed information about genetic polymorphisms associated with different Kidd phenotypes.[19] Microarray technology enables simultaneous analysis of multiple blood group antigens, including those in the Kidd system. This high-throughput method is efficient for large-scale screenings and can help identify rare phenotypes that might not be detectable through traditional serological methods.[20] Sanger sequencing can be used to analyze exons and intron-exon borders of the Kidd gene, providing comprehensive information about mutations and polymorphisms. This method is particularly valuable for identifying novel variants and understanding their clinical implications.[21] Accurate determination of Kidd blood group antigens is crucial in transfusion medicine due to their association with delayed hemolytic transfusion reactions and hemolytic disease of the newborn. Although serological methods are quick and useful for initial assessments, molecular techniques offer higher sensitivity and specificity, especially in complex clinical scenarios, such as recent transfusions or autoimmune conditions. The choice of method often depends on available resources, clinical requirements, and the need for accuracy in transfusion matching.[18]

Prevention of transfusion reactions due to the Kidd blood group system requires a unified and interprofessional medical team to enhance patient safety and transfusion outcomes. Every healthcare staff in the transfusion chain plays a critical role in patient safety. The healthcare staff must check for an additional Kidd antigen-negative blood unit with all mandatory pretransfusion checks during the planning of transfusion in patients with Kidd antibodies. All healthcare staff should know their responsibilities in the transfusion team. During transfusing blood products, nurses and clinicians should be proficient in promptly identifying transfusion reactions and possible complications while implementing close monitoring and preventive strategies to handle adversities. Obtaining informed consent from patients regarding anti-Kidd antibodies is crucial for respecting their autonomy and ensuring beneficence and non-maleficence. In managing adverse transfusion events caused by kidd antibodies, an interprofessional healthcare team can ensure better responsiveness, minimize complications, and prioritize patient safety. Further research should be conducted on the role of the SLC14A1 gene and its functional protein in various diseases, along with the transfusion outcomes and its clinical sequelae.