Lecture 9 – Kell, Kidd and Duffy System PDF

SCIE 2040 – Transfusion Medicine 1 Textbook Chapter 6 Lecture 9 – Kell, Kidd and Duffy System 6 Other Antigen Systems 6.1 Antigens and Enzymes Manufacturers of commercial red blood cells typically provide a paper antigram that lists the antigen profiles of the...

SCIE 2040 – Transfusion Medicine 1 Textbook Chapter 6 Lecture 9 – Kell, Kidd and Duffy System 6 Other Antigen Systems 6.1 Antigens and Enzymes Manufacturers of commercial red blood cells typically provide a paper antigram that lists the antigen profiles of the cells to assist in antibody identification. The antigens primarily tested for and documented include, at minimum, those to which alloantibodies are most often found. In addition to ABO and Rh antigens, other antigens frequently documented include: K, k, Fya, Fyb, Jka, Jkb, Lea, Leb , P1, M, N, S, and s Lua, Lub and Xga are also often included To further assist in antibody identification, cells can be treated by enzymes in the lab or purchased pre-treated. Proteolytic enzymes remove some structures from structures from the red cell surface, but also help expose other structures. Ficin (figs) is used most often, but other enzymes include papain (papaya), bromelin (pineapple) and trypsin (hog stomach lining). Enhanced by Enzymes Destroyed Unaffected Enzymes destroy some antigens, ABO/H and related Duffy Kell eliminating reactivity with the systems: MNSs corresponding antibody. Some other Lewis Xga I antigens, such as those in the Rh P system, are enhanced by enzymes, Rh causing the cell’s reactivity with Kidd corresponding antibodies to increase. 6.2 Lewis, I and H Notable Lea Leb Antigens: European 22 72 Frequency (%): Reaction with Enhanced enzymes: Antigen on No fetal cells: Antibody: Anti-Lea Anti-Leb Usual class: IgM 1 SCIE 2040 – Transfusion Medicine 1 Textbook Chapter 6 Usual Lewis, I and H were discussed None Significance: alongside ABO in Chapter 4. All are enhanced on enzyme-treated cells. Neither Lewis nor I antigens are present on cells at birth. Antibodies found against these antigens are clinically insignificant IgM (aside from Bombay anti-H). I and H antigens are not explicitly documented on antigrams (as both are high- incidence) but anti-I, anti-H and anti-IH autoantibodies can interfere with alloantibody identification testing, especially when using enzyme treated cells. 6.3 Kell and Kx Blood Group Systems Of the over 30 antigens in the Notable Kell blood group system, the K k Antigens: antithetical K and k antigens European 9 > 99 are the most important. The Frequency (%): antigens of the Kell system are Reaction with Unaffected found on a glycoprotein that Enzymes: Antigen on fetal passes through the red blood Yes cell membrane once, coded for cells: by the KEL gene, located on Antibody: Anti-K Anti-k chromosome 7. Roughly 9% of IgG the population is K+ but over Usual class: IgG (Rare) Occasionally IgM 99% of the population is k+, Usual making k a high-incidence HTR or HDFN Significance: antigen. Aside from D, the K antigen is the next most immunogenic, with transfusion with K-positive red blood cells resulting in production of IgG anti-K about 10% of the time. This antibody is very clinically significant, responsible for hemolytic transfusion reactions and severe hemolytic disease of the fetus and newborn (HDFN). Anti-K may also (rarely) be detected as an IgM antibody, usually in association with bacterial infections. The antithetical antigen pairs of Penny (Kpa and Kpb) and Sutter (Jsa and Jsb) are also located on the Kell protein: Kpb, and Jsb are high-incidence Kpa and Jsa are low-incidence The Kell protein structure is held together by disulfide bonds. Reducing agents including dithiothreitol (DTT) or 2-mercaptoethanol (2-ME) break disulfide bonds and will destroy Kell system antigens. However, Kell is unaffected by enzymes like ficin. 2 SCIE 2040 – Transfusion Medicine 1 Textbook Chapter 6 Very rarely, an individual may inherit of a double dose of the silent allele Ko, resulting in a null phenotype with a total lack of Kell antigens. They produce an antibody known as anti-Ku, which reacts with all cells except other Ko cells. The gene XK, carried on the X chromosome results in production of the high- incidence antigen Kx. Although the XK and KEL genes are on separate chromosomes, their protein products are linked by disulfide bond. A nonfunctional or deleted XK gene results in the very rare McLeod phenotype, which lacks Kx along with a high-incidence Kell antigen known as Km. Once transfused, patients with the McLeod phenotype may produce anti-KL, a mixture of anti-Kx and anti- Km. The McLeod phenotype is also associated with a hereditary form of chronic granulomatous disease (CGD), an X-linked hereditary condition leading to phagocyte defects and a predisposition to infection. 6.4 Kidd Blood Group System The glycoprotein carrying the Notable Jka Jkb Kidd blood group system antigens Antigens: European transports urea across the red Frequency 77 51 blood cell membrane. (%): There are three antigens in the Reaction with Kidd system: Jka, Jkb, and the Enhanced enzymes: high-incidence antigen, Jk3, Antigen on which is present alongside Jka Yes fetal cells: and/or Jkb. Roughly 77% of individuals are Jka+ and 51% are Antibody: Anti- Jka Anti- Jkb Jkb+. The Kidd antigens are fully developed at birth. Enzyme Usual class: IgG (complement binding) treatment generally enhances Kidd antigen expression. Usual HTR or HDFN Significance: The silent JK gene, although rare, is more common in people of Polynesian ethnicity. Those homozygous for this gene will phenotype as Jk(a–b–) and lack the Jk3 antigen. Anti-Jka or anti-Jkb may cause severe HDFN. Moreover, both anti-Jka and anti-Jkb are notorious for causing delayed hemolytic transfusion reactions, for two reasons: 1. The antibodies can drop below serologically detectable levels within months of production. Therefore, a patient who previously developed, for example, an anti-Jka may now present with a negative antibody screen. If there is no historical record of the antibody, the patient may be transfused with Jka- 3 SCIE 2040 – Transfusion Medicine 1 Textbook Chapter 6 positive cells. When this happens, the anti-Jka titer rises rapidly in an anamnestic response. 2. The IgG antibodies of the Kidd blood group system are very good at binding complement. This results in often severe hemolysis and a rapid drop in hemoglobin to pretransfusion levels. The use of polyspecific AHG reagent, which can detect bound complement, can assist in the identification of a Kidd system antibody. 6.5 Duffy Blood Group System There are six antigens in the Notable Fya Fyb Duffy blood group system, but of Antigens: European primary concern is the allelic pair Frequency 66 83 Fya and Fyb. Approximately 66% (%): of Europeans are Fya+ and about Reaction with 83% are Fyb+. The other antigens Destroyed Enzymes: (Fy3 – Fy6) are high-incidence. Antigen on The Duffy antigens are well Yes fetal cells: developed at birth, though they Antibody: Anti- Fya Anti- Fyb have been reported to weaken upon storage of red blood cells. Fya and Fyb antigens are Usual class: IgG destroyed by enzyme treatment. Usual A weak expression of the Fyb HTR or HDFN HTR Significance: antigen, which is called Fyx, occasionally occurs in people of European ethnicity. Conversely, the Fy(a–b–) phenotype is common in people of African ethnicity, occurring in about 70% of this population. The phenotype changes the red blood cell membrane, resulting in increased resistance to malarial infections by Plasmodium vivax. Because of the prevalence of the silent FY gene in Black populations, the genetics behind the common Duffy phenotypes, and the resulting dosage effects, may differ between people of African and European ethnicity. The Duffy antibodies are IgG and do not bind complement. Anti-Fya may cause severe HDFN but rarely does anti-Fyb. However, both may cause hemolytic transfusion reactions. 4