Lutheran system

Lutheran system. By Sydney Call & Jess Rogers.

Objectives. 1. Describe the properties of the Lutheran system in terms of: a. Clinical significance of alloantibodies produced b. Immunogenicity of antigen c. Antibody specificity d. Antigenic dosage e. Number and location sites on the cell f. Modes of inheritance g. Incidence h. Antigen development (presence on fetal cells) i. Known biological function of antigen, if applicable j. Correlation with disease states k. Reactivity after enzyme treatment.

Objectives Cont.. 2. Explain the background of this blood group system’s unique name. 3. Describe the following antigens in terms of antigen frequency and describe the clinical significance of the antibodies directed against them: a. Lua b. Lub c. Lu3 4. Compare and contrast the in vitro characteristics of the following Alloantibodies: a. Anti-Lua b. Anti-Lub c. Anti-Lu3.

[Audio] A little background about the discovery of blood groups systems. It started in 1900 by Karl Landsteiner who discovered why some blood transfusions were successful while others were not. He discovered the ABO blood group system in 1940 and continued to discover the M and N, P, and Rh systems. Landsteiner found that there are substances in the blood, antigens and antibodies, that induce clumping of red cells when red cells of one type are added to those of a second type. He recognized three groups—A, B, and O—based on their reactions to each other. A fourth group, AB, was identified a year later by another research team. The discovery of the Rh system by Landsteiner and Alexander Wiener in 1940 was made because they tested human red cells with antisera developed in rabbits and guinea pigs by immunization of the animals with the red cells of the rhesus monkey Macaca mulatta. With the discovery of the ABO and RH systems it was easier to discover other antigens or antibodies that were causing reactions that were independent of the ABO and RH systems. The first Blood group system that was not discovered by Karl Landsteiner was the Lutheran system which was discovered by Callender, Race & Paykop in 1945. The first example of anti-Lua was discovered in the serum of a patient following transfusion of a unit of blood carrying the corresponding low frequency antigen. The new antibody was named Lutheran which was a misinterpretation of the patient's name, Luteran. They showed that the Lutheran system was independent of the ABO, Rh, M N, and P blood group systems ( 1946)..

[Audio] Lutheran antigens are all different variations of the basal cell adhesion molecule. There are 19 known antigens in the lutheran system. Four pairs of anti-thetical antigens and 11 high frequency antigens. The antigens are located on four out of the five immunoglobulins domains of both the isoforms of the lutheran glycoprotein. The Lutheran gene is located on chromosome 19. The whole system is based on the expression of two codominant alleles designated Lua and Lub. There was antigens known as Au^a and Au^ b also called the Auberget antigens that also come from the basal cell adhesion molecule gene which was later discovered to be Lutheran antigens coming off of the basal cell adhesion molecule gene and not a new blood group system. Most of the Lutheran BGS antigens are high prevalence, with Lua, Aua and Aub being polymorphic and only Lu9 and Lu14 being low prevalence. Lutheran antigens and antibodies tend to result in agglutination that gives a characteristic loose agglutination, with many non agglutinated red cells. An expert and experienced blood group serologist can sometimes use this characteristic agglutination to guide them towards recognising an antibody directed against an antigen within the Lutheran.

[Audio] Lua is expressed on fetal cells as well as placental cells which prevents antibody transfer to the fetus. There is no visible impact on the pregnancy With respect to HDFN, fetal Lua is often present on placental tissues; consequently, adsorption of maternal IgG antibodies onto placental cells prevents antibody transfer to the fetus. This has no apparent impact on pregnancy viability..

[Audio] The Lutheran system is unaffected by the most common enzymes including Ficin, Papain, and bromelain. The use of either DTT, Trypsin, and a-chymotrypsin will reduce or destroy the antigens. The Lutheran system is typically IgM but may have some associations with IgG and IgA components in LuB. The antigens react at both warm and cold phases depending on phenotype. Lub will react with all cells tested except for the auto control because of 99% of cells express the Lub antigen and the reactions are typically weaker with the dosage effect of (a+,b+).

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[Audio] Primary function of the Lutheran glycoproteins on the red blood cells could involve the maturing red blood cells from the bone marrow and into the peripheral circulation. They could also be involved in the vascular occlusion and thrombotic events as complications of sickle cell disease and polycythemia vera..

[Audio] Lutheran antigens and antibodies tend to result in agglutination that gives a characteristic loose agglutination, with many non-agglutinated red cells. An expert and experienced blood group serologist can sometimes use this characteristic agglutination to guide them towards recognising an antibody directed against an antigen within the Lutheran BGS. The lutheran system generally has relatively benign reactions. When there is reaction they are generally only mild to delayed hemolytic transfusion reactions and Hemolytic disease of the fetus and newborn. Caused by LuB Some symptoms of transfusion reactions are: back pain, blood in the urine, fever, chills, fainting, flushing of the skin and flank pain. To treat a transfusion reaction the transfusion should be stopped immediately as well as keeping the line open with normal saline. Intervene as signs and symptoms appear and monitor vitals..

[Audio] In Hemolytic disease of the fetus and newborn symptoms consider of pale skin, yellowing of the amniotic fluid, umbilical cord, skin, and eyes. Along with enlargement of the liver or spleen and swelling of the body. Symptoms change during pregnancy which can results in mild anemias, hyperbilirubinemia with jaundice or more severe anemias with enlargement of the liver and speen. In some cases hydrops fetalis is also a possibility. Treatment can include feeding often with extra fluids and light therapy in infants. Anti-LuA can have no immediate hemolytic translation reaction or an relayed reaction. It is rare to see hemolytic disease of the fetus and newborn with anti-Lua. Anti-LuB is the antigen that causes the majority of the reactions due it being low incidence..

[Audio] Throughout the population there are different frequencies within the population, one of the most common frequencies is Lu(a-,b+) whereas the most rare frequency is Lu(a-,b-). • As you can see, the probability of a patient forming anti-Lua would be low, because 92% of the donor population is Lua negative. • Conversely, Lub is a high incidence antigen. The probability of a patient forming anti-Lub is also low, because 0.15% and fewer lack this antigen. The lutheran system is antigenic expression is highly variable among individuals. Antigen development is starts early in age and has poor expression until around fifteen years of age..

[Audio] The Table above shows the different Lutheran phenotypes that we have been discussing. The table indicates that the most common phenotype over different populations is Lu(a-,b+) whereas, the most rate is the Lu(a+,b-)..

[Audio] The dosage effect is a different in antibody reaction strength depending on the quantity of the target antigen present on a target red blood cell . Like most blood group systems the alleles are inherited in a codominant manner. If a individual inherited alleles for both LuA and Lub antigens than both will be expressed on the red blood cells. Because both of the antigens are expressed on the same cell they are considered to have single dosage. When an individual inherits a homozygous allele than an individual is also know to have double dosage. An antibody against LUa may react significantly stronger when mixed with an Lua+ b- than with a double dose which was Lua a+,b+ which has less of the Lua which is the stronger antigen to test for because it is present on 99% of cells..

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[Audio] Anti-Lua are often IgM saline agglutinins reacting at 18°C or below but may also be partly IgG and react by the antiglobulin technique. Mild cases of hemolytic disease of the newborn have been reported, but anti- Lua has not been clearly incriminated as a cause of increased red cell destruction. With respect to HDFN, fetal Lua is often present on placental tissues; consequently, adsorption of maternal IgG antibodies onto placental cells prevents antibody transfer to the fetus. This has no apparent impact on pregnancy viability. when anti-Lua is detected in a patient's pre-transfusion sample, there is usually no requirement for selection of Lua-negative donor red blood cells. In fact, 92% of donor units are Lua-negative..

Clinical significance Continued. Antigen Reaction Temp Anti- Lua Room temp and 37°C Anti-Lub 37°C.

[Audio] When performing the test tube method, you can see loose mixed field reactions when doing typing screens. Other than that, there is no in vitro hemolysis that is seen in the lutheran system..

[Audio] In the Lu system there is a type of Lu(a-b-) that arises from homozygous inheritance of an amorphic recessive gene Lu at the Lu locus. However this type is far less common than the In(Lu) type..

Citations. Image 1- Kennedy, John. “Karl Landsteiner Doodle Celebrates Discoverer of Blood Groups.” Silicon Republic , 14 June 2016, www.siliconrepublic.com/trending/karl-landsteiner-google-doodle . Image 2-Anstee, David J. “Red Cell Genotyping and the Future of Pretransfusion Testing.” Blood , vol. 114, no. 2, American Society of Hematology, July 2009, pp. 248–56. Crossref , https://doi.org/10.1182/blood-2008-11-146860. Chart 1- Press, Dove, et al. “Phenotype Frequencies of Major Blood Group Systems (Rh, Kell, Kidd, Du | JBM.” Phenotype Frequencies of Major Blood Group Systems (Rh, Kell, Kidd, Du | JBM , www.dovepress.com/phenotype-frequencies-of-major-blood-group-systems-rh-kell-kidd-duffy--peer-reviewed-fulltext-article-JBM. Accessed 14 Oct. 2022. Britannica, The Editors of Encyclopaedia. "Lutheran blood group system". Encyclopedia Britannica, 15 Feb. 2019, https://www.britannica.com/science/Lutheran-blood-group-system. Accessed 2 October 2022. Farhud DD, Zarif Yeganeh M. A brief history of human blood groups. Iran J Public Health. 2013;42(1):1-6. Epub 2013 Jan 1. PMID: 23514954; PMCID: PMC3595629. Lutheran system: anti-Lua. (n.d.). Professional Education. Retrieved October 11, 2022, from https://professionaleducation.blood.ca/en/transfusion/best-practices/serological-best-practices/lutheran-system-anti-lua Needs, Malcom. “THE LUTHERAN BLOOD GROUP SYSTEM.” https://www.thebiomedicalscientist.net, 1 Mar. 2018, www.thebiomedicalscientist.net/science/lutheran-blood-group-system ..

Citations Continued. Thornton, Nicole. “The Clinical Significance of Blood Group Alloantibodies and the Supply of Blood for Transfusion.” SPN214/4 the Clinical Significance of Blood Group, 11 Jan. 2013, chrome-extension://efaidnbmnnnibpcajpcglclefindmkaj/ https://nhsbtdbe.blob.core.windows.net/umbraco-assets-corp/14863/spn2144-the-clinical-significance-of-blood-group-alloantibodies-and-the-supply-of-blood-for-transfusion.pdf . “Blood Group - the Importance of Antigens and Antibodies.” Encyclopedia Britannica , www.britannica.com/science/blood-group/The-importance-of-antigens-and-antibodies. Accessed 14 Oct. 2022. RBC image- Smart, Elizabeth, and Beryl Armstrong. “Blood Group Systems.” ISBT Science Series , vol. 15, no. S1, Wiley, Dec. 2020, pp. 123–50. Crossref , https://doi.org/10.1111/voxs.12593 . Amoeba sister Gif and images- “Amoeba Sisters GIFs.” Science With the Amoeba Sisters , www.amoebasisters.com/gifs.html. Accessed 14 Oct. 2022..