The document summarizes information about blood group systems and the Kidd blood group system. It discusses that there are over 30 recognized blood group systems in addition to ABO and Rh, including the Kidd system. The Kidd system involves the Jka and Jkb antigens which are carried on the SLC14A1 glycoprotein and can cause hemolytic transfusion reactions. It notes that a patient developed anti-Jkb antibodies after transfusions and now requires Jkb negative blood, which can be difficult to find due to availability and donor frequencies of the antigen.

1. 09/05/11 Laboratory Services and Consultations Limited Presents Case Review 27 th August 2011 Susan Forde

2. Human blood group systems The International Society of Blood Transfusion (ISBT) currently recognises 30 major blood group systems (including the ABO and Rh systems). Thus, in addition to the ABO antigens and Rhesus antigens, many other antigens are expressed on the red blood cell surface membrane. For example, an individual can be AB RhD positive, and at the same time M and N positive (MNS system), K positive (Kell system), and Lea or Leb positive (Lewis system). Many of the blood group systems were named after the patients in whom the corresponding antibodies were initially encountered. The ISBT definition of a blood group system is where one or more antigens are "controlled at a single gene locus or by two or more very closely linked homologous genes with little or no observable recombination between them" 09/05/11

3. The most common type of grouping is the ABO grouping. The varieties of protein coating on red blood cells divides blood into four groups: A (A oligosaccharide is present) B (B oligosaccharide is present) AB (A and B oligosaccharides are present) O (neither A nor B, only their precursor H oligosaccharide present) 09/05/11

4. There are subtypes under this grouping (listed as A1, A2, A1B or A2B…) some of which are quite rare. Apart from this there is a protein which plays an important part in the grouping of blood. This is called the Rh factor. If this is present, the particular blood type is called positive. If it is absent, it is called negative. Thus we have the following broad categories: A1 Negative (A1 -ve) A1 Positive (A1 +ve) A1B Negative (A1B -ve) A1B Positive (A1B +ve) A2 Negative (A2 -ve) A2 Positive (A2 +ve) A2B Negative (A2B -ve) A2B Positive (A2B +ve) B Negative (B -ve) B Positive (B +ve) B1 Positive (B1 +ve) O Negative (O -ve) O Positive (O +ve) Rare blood types In the "ABO" system, all blood belongs to one of four major groups: A, B, AB, or O. But there are more than two hundred minor blood groups that can complicate blood transfusions. These are known as rare blood types. Whereas common blood types are expressed in a letter or two, with maybe a plus or a minus, a smaller number of people express their blood type in an extensive series of letters in addition to their 'ABO' type designation. 09/05/11

5. Blood group systems 09/05/11 ISBT № System name System symbol Epitope or carrier, notes Chromosome 001 ABO ABO Carbohydrate (N-Acetylgalactosamine, galactose). A, B and H antigens mainly elicit IgM antibody reactions, although anti-H is very rare, see the Hh antigen system (Bombay phenotype, ISBT #18). 9 002 MNS MNS GPA / GPB (glycophorins A and B). Main antigens M, N, S, s. 4 003 p P1. Glycolipid. Antigen P1. 22 004 Rh RH Protein. C, c, D, E, e antigens (there is no "d" antigen; lowercase "d" indicates the absence of D). 1 005 Lutheran LU Protein (member of the immunoglobulin superfamily). Set of 21 antigens. 19 006 Kell KEL Glycoprotein. K1 can cause hemolytic disease of the newborn (anti-Kell), which can be severe. 7 007 Lewis LE Carbohydrate (fucose residue). Main antigens Lea and Leb - associated with tissue ABH antigen secretion. 19

6. 09/05/11 ISBT № System name System symbol Epitope or carrier, notes Chromosome 008 Duffy FY Protein (chemokine receptor). Main antigens Fya and Fyb. Individuals lacking Duffy antigens altogether are immune to malaria caused by Plasmodium vivax and Plasmodium knowlesi . 1 009 Kidd JK Protein (urea transporter). Main antigens Jka and Jkb 18 010 Diego DI Glycoprotein (band 3, AE 1, or anion exchange). Positive blood is found only among East Asians and Native Americans. 17 011 Yt or Cartwright YT Protein (AChE, acetylcholinesterase). 7 012 XG XG Glycoprotein X 013 Scianna SC Glycoprotein 1 014 Dombrock DO Glycoprotein (fixed to cell membrane by GPI, or glycosyl-phosphatidyl-inositol). 12

7. 09/05/11 ISBT № System name System symbol Epitope or carrier, notes Chromosome 015 Colton CO Aquaporin 1. Main antigens Co(a) and Co(b). 7 016 Landsteiner-Wiener LW Protein (member of the immunoglobulin superfamily). 19 017 Chido/Rodgers CH/RG C4A C4B (complement fractions). 6 018 Hh/Bombay H Carbohydrate (fucose residue). 19 019 Kx XK Glycoprotein. X 020 Gerbich GE GPC / GPD (Glycophorins C and D). 2 021 Cromer CROM Glycoprotein (DAF or CD55, regulates complement fractions C3 and C5, attached to the membrane by GPI). 1 022 Knops KN Glycoprotein (CR1 or CD35, immune complex receptor). 1

8. 09/05/11 ISBT № System name System symbol Epitope or carrier, notes Chromosome 023 Indian IN Glycoprotein (CD44 adhesion function?). 11 024 OK OK Glycoprotein (CD147). 19 025 Raph MER2 Transmembrane glycoprotein. 11 026 JMH JMH Protein (fixed to cell membrane by GPI). 6 027 Ii I Branched (I) / unbranched (i) polysaccharide 6 028 Globoside GLOB Glycolipid. Antigen P. 3 029 GIL GIL Aquaporin 3. 9 030 Rh-associated glycoprotein RHAG Rh-associated glycoprotein 6

9. KIDD BLOOD GROUP SYSTEM Anti Jka and Anti Jkb Anti Jka was first recognized in 1951 in the serum of a woman who had given birth to a child with Haemolytic Disease of the Newborn (HDN). Two years later anti Jkb was found in the serum of patient who had suffered a transfusion reaction. These antibodies are often weak when first detected and, perhaps because they are detected indirectly through the complement that they bind to red cells, some may become undetectable on storage. Serum containing weak anti Jka or anti Jkb, even when freshly drawn, may manifest a dosage effect, reacting only with red cells expressing a double dose of the antigen. As our patient has a weakly reacting antibody, it is also imperative that the donor cells are tested with a very sensitive commercially prepared monoclonal Anti Jkb as well as being cross matched with the patient serum. 09/05/11

10. CLINICAL SIGNIFICANCE Kidd system antibodies occasionally cause HDN, but the HDN is usually mild. However these antibodies are notorious for involvement in severe Haemolytic Transfusion Reaction (HTR), especially delayed haemolytic reactions (DHTRs) DHTRs occur when antibody develops so rapidly in an anamnestic response to antigens on transfused red cells that it destroys the still circulating red cells. In many cases re-testing the patient’s pre transfusion serum confirms that the antibody was indeed undetectable in the original testing. This highlights the importance of consulting previous records before selecting blood for transfusion. Patients whose antibody has been detected and identified can be protected against repeated contact with the known immunizing stimulus. 09/05/11

11. ANTIGENS OF THE KIDD BLOOD GROUP SYSTEM Antigen specificity Protein Amino acid sequence determines the specificity of Kidd antigens. Antigen carrying Glycoprotein that The Kidd protein is a trans membrane molecules transports urea multi-pass protein that transports Urea across the red cell membrane. Molecular basis The SLC14A1 gene Located on Chromosome 18 encodes the Kidd glycoprotein ((18q11-q12) 09/05/11

12. PHENOTYPES AND FREQUENCIES IN THE KIDD SYSTEM Reactions Adult Phenotype with Anti Frequency % Jka Jkb Phenotype Whites Blacks + 0 Jk(a+b-) 26 51 + + Jk(a+b+) 51 41 0 + Jk(a-b+) 23 8 0 0 Jk (a-b-) extremely rare 09/05/11

13. Our patient has developed Anti Jkb after numerous transfusions, and therefore requires blood that is Jkb negative. From the above table with our mixed population of blood donors we could optimistically expect 30-40% to be compatible. However we were not so lucky, one time we tested 12 units before we found 2 compatible Jkb Negative donors. Our patient is Group O Positive and therefore can only be transfused with group O blood, which is always the group most in demand, and has a frequency around 48% in both Whites and Blacks. 09/05/11

14. Thank You Any Questions? 09/05/11