P1PK blood group system

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Structures of P1PK blood group antigens 2020 10 14 P1PK antigen structures.png
Structures of P1PK blood group antigens

P1PK (formerly: P) is a human blood group system (International Society of Blood Transfusion system 003) based upon the A4GALT gene on chromosome 22. The P antigen (later renamed P1) was first described by Karl Landsteiner and Philip Levine in 1927. [1] The P1PK blood group system consists of three glycosphingolipid antigens: Pk, P1 and NOR. [2] [3] In addition to glycosphingolipids, terminal Galα1→4Galβ structures are present on complex-type N-glycans. [4] The GLOB antigen (formerly P) is now the member of the separate GLOB (globoside) blood group system.

Contents

P1PK antigens

The P1PK antigens are carbohydrate antigens that include Pk (Gb3), P1 and NOR1, NORint and NOR2. All are synthesized by Gb3/CD77 synthase (α1,4-galactosyltransferase, P1/Pk synthase). [5]

The presence or absence of P1 antigen depends on the A4GALT transcript level. It was found that differential binding of transcription factors early growth response 1 (EGR1) and runt-related transcription factor 1 (RUNX1) to the SNP rs5751348 [9] genomic region with the different genotypes in the A4GALT gene leads to differential activation of A4GALT expression, leading to two genotypes: P1 and P2. [10] [11]

P1PK phenotypes

P1PK phenotypes are defined by reactivity to antibodies to anti-P1, anti-P, anti-Pk anti-PP1Pk. and anti-NOR antibodies.

P1PK antibodies

Interpretation of antibody panel to detect patient antibodies towards the most relevant human blood group systems, including P1P .
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Further information: Blood compatibility testing Serology interpretation of antibody panel for blood group antigens.jpg
Interpretation of antibody panel to detect patient antibodies towards the most relevant human blood group systems, including P1P .

Antibody detection

Anti-P1Pk antibodies are not usually detected with routine laboratory methods. It is possible to detect them using the Donath-Landsteiner test. This test is performed on 2 vials of blood at two different temperatures: 4 °C and 37 °C (body temperature). A test is interpreted as positive only after a patient's red blood cells have been incubated at both temperatures and subsequently hemolyzed. [17]

Related Research Articles

<span class="mw-page-title-main">Blood type</span> Classification of blood based on antibodies and antigens on red blood cell surfaces

A blood type is a classification of blood, based on the presence and absence of antibodies and inherited antigenic substances on the surface of red blood cells (RBCs). These antigens may be proteins, carbohydrates, glycoproteins, or glycolipids, depending on the blood group system. Some of these antigens are also present on the surface of other types of cells of various tissues. Several of these red blood cell surface antigens can stem from one allele and collectively form a blood group system.

Rh disease is a type of hemolytic disease of the fetus and newborn (HDFN). HDFN due to anti-D antibodies is the proper and currently used name for this disease as the Rh blood group system actually has more than 50 antigens and not only the D-antigen. The term "Rh Disease" is commonly used to refer to HDFN due to anti-D antibodies, and prior to the discovery of anti-Rho(D) immune globulin, it was the most common type of HDFN. The disease ranges from mild to severe, and occurs in the second or subsequent pregnancies of Rh-D negative women when the biologic father is Rh-D positive.

<span class="mw-page-title-main">Hemolytic disease of the newborn</span> Fetal and neonatal alloimmune blood condition

Hemolytic disease of the newborn, also known as hemolytic disease of the fetus and newborn, HDN, HDFN, or erythroblastosis fetalis, is an alloimmune condition that develops in a fetus at or around birth, when the IgG molecules produced by the mother pass through the placenta. Among these antibodies are some which attack antigens on the red blood cells in the fetal circulation, breaking down and destroying the cells. The fetus can develop reticulocytosis and anemia. The intensity of this fetal disease ranges from mild to very severe, and fetal death from heart failure can occur. When the disease is moderate or severe, many erythroblasts are present in the fetal blood, earning these forms of the disease the name erythroblastosis fetalis.

The direct and indirect Coombs tests, also known as antiglobulin test (AGT), are blood tests used in immunohematology. The direct Coombs test detects antibodies that are stuck to the surface of the red blood cells. Since these antibodies sometimes destroy red blood cells they can cause anemia; this test can help clarify the condition. The indirect Coombs test detects antibodies that are floating freely in the blood. These antibodies could act against certain red blood cells; the test can be carried out to diagnose reactions to a blood transfusion.

Paroxysmal cold hemoglobinuria (PCH) or Donath–Landsteiner hemolytic anemia (DLHA) is an autoimmune hemolytic anemia featured by complement-mediated intravascular hemolysis after cold exposure. It can present as an acute non-recurrent postinfectious event in children, or chronic relapsing episodes in adults with hematological malignancies or tertiary syphilis. Described by Julius Donath (1870–1950) and Karl Landsteiner (1868–1943) in 1904, PCH is one of the first clinical entities recognized as an autoimmune disorder.

In ABO hemolytic disease of the newborn maternal IgG antibodies with specificity for the ABO blood group system pass through the placenta to the fetal circulation where they can cause hemolysis of fetal red blood cells which can lead to fetal anemia and HDN. In contrast to Rh disease, about half of the cases of ABO HDN occur in a firstborn baby and ABO HDN does not become more severe after further pregnancies.

Hemolytic disease of the newborn (anti-Kell1) is the second most common cause of severe hemolytic disease of the newborn (HDN) after Rh disease. Anti-Kell1 is becoming relatively more important as prevention of Rh disease is also becoming more effective.

Hemolytic disease of the newborn (anti-Rhc) can range from a mild to a severe disease. It is the third most common cause of severe HDN. Rh disease is the most common and hemolytic disease of the newborn (anti-Kell) is the second most common cause of severe HDN. It occurs more commonly in women who are Rh D negative.

The Kell antigen system is a human blood group system, that is, a group of antigens on the human red blood cell surface which are important determinants of blood type and are targets for autoimmune or alloimmune diseases which destroy red blood cells. The Kell antigens are K, k, Kpa, Kpb, Jsa and Jsb. The Kell antigens are peptides found within the Kell protein, a 93-kilodalton transmembrane zinc-dependent endopeptidase which is responsible for cleaving endothelin-3.

The Kidd antigen system are proteins found in the Kidd's blood group, which act as antigens, i.e., they have the ability to produce antibodies under certain circumstances. The Jk antigen is found on a protein responsible for urea transport in the red blood cells and the kidney. They are important in transfusion medicine. People with two Jk(a) antigens, for instance, may form antibodies against donated blood containing two Jk(b) antigens. This can lead to hemolytic anemia, in which the body destroys the transfused blood, leading to low red blood cell counts. Another disease associated with the Jk antigen is hemolytic disease of the newborn, in which a pregnant woman's body creates antibodies against the blood of her fetus, leading to destruction of the fetal blood cells. Hemolytic disease of the newborn associated with Jk antibodies is typically mild, though fatal cases have been reported.

<span class="mw-page-title-main">Rh blood group system</span> Human blood group system involving 49 blood antigens

The Rh blood group system is a human blood group system. It contains proteins on the surface of red blood cells. After the ABO blood group system, it is the most likely to be involved in transfusion reactions. The Rh blood group system consisted of 49 defined blood group antigens in 2005. As of 2023, there are over 50 antigens among which the five antigens D, C, c, E, and e are the most important. There is no d antigen. Rh(D) status of an individual is normally described with a positive (+) or negative (−) suffix after the ABO type. The terms Rh factor, Rh positive, and Rh negative refer to the Rh(D) antigen only. Antibodies to Rh antigens can be involved in hemolytic transfusion reactions and antibodies to the Rh(D) and Rh antigens confer significant risk of hemolytic disease of the newborn.

The MNS antigen system is a human blood group system based upon two genes on chromosome 4. There are currently 50 antigens in the system, but the five most important are called M, N, S, s, and U.

The Lewis antigen system is a human blood group system. It is based upon two genes on chromosome 19: FUT3, or Lewis gene; and FUT2, or Secretor gene. Both genes are expressed in glandular epithelia. FUT2 has a dominant allele which codes for an enzyme and a recessive allele which does not produce a functional enzyme. Similarly, FUT3 has a functional dominant allele (Le) and a non-functional recessive allele (le).

<span class="mw-page-title-main">Ii antigen system</span> Human blood group system

The Ii antigen system is a human blood group system based upon a gene on chromosome 6 and consisting of the I antigen and the i antigen. The I antigen is normally present on the cell membrane of red blood cells in all adults, while the i antigen is present in fetuses and newborns.

<span class="mw-page-title-main">A4GALT</span> Protein-coding gene in the species Homo sapiens

Lactosylceramide 4-alpha-galactosyltransferase is an enzyme that in humans is encoded by the A4GALT gene.

The Vel blood group is a human blood group that has been implicated in hemolytic transfusion reactions. The blood group consists of a single antigen, the high-frequency Vel antigen, which is expressed on the surface of red blood cells. Individuals are typed as Vel-positive or Vel-negative depending on the presence of this antigen. The expression of the antigen in Vel-positive individuals is highly variable and can range from strong to weak. Individuals with the rare Vel-negative blood type develop anti-Vel antibodies when exposed to Vel-positive blood, which can cause transfusion reactions on subsequent exposures.

The Junior blood group system is a human blood group defined by the presence or absence of the Jr(a) antigen, a high-frequency antigen that is found on the red blood cells of most individuals. People with the rare Jr(a) negative blood type can develop anti-Jr(a) antibodies, which may cause transfusion reactions and hemolytic disease of the newborn on subsequent exposures. Jr(a) negative blood is most common in people of Japanese heritage.

<span class="mw-page-title-main">Blood compatibility testing</span> Testing to identify incompatibilities between blood types

Blood compatibility testing is conducted in a medical laboratory to identify potential incompatibilities between blood group systems in blood transfusion. It is also used to diagnose and prevent some complications of pregnancy that can occur when the baby has a different blood group from the mother. Blood compatibility testing includes blood typing, which detects the antigens on red blood cells that determine a person's blood type; testing for unexpected antibodies against blood group antigens ; and, in the case of blood transfusions, mixing the recipient's plasma with the donor's red blood cells to detect incompatibilities (crossmatching). Routine blood typing involves determining the ABO and RhD type, and involves both identification of ABO antigens on red blood cells and identification of ABO antibodies in the plasma. Other blood group antigens may be tested for in specific clinical situations.

The Lan blood group system is a human blood group defined by the presence or absence of the Lan antigen on a person's red blood cells. More than 99.9% of people are positive for the Lan antigen. Individuals with the rare Lan-negative blood type, which is a recessive trait, can produce an anti-Lan antibody when exposed to Lan-positive blood. Anti-Lan antibodies may cause transfusion reactions on subsequent exposures to Lan-positive blood, and have also been implicated in mild cases of hemolytic disease of the newborn. However, the clinical significance of the antibody is variable. The antigen was first described in 1961, and Lan was officially designated a blood group in 2012.

<span class="mw-page-title-main">Elwira Lisowska</span> Polish biochemist and professor

Elwira Lisowska is a Polish biochemist and professor. She made significant contributions to the biochemistry of human blood groups, especially MNS and P1PK blood group systems, and to the immunochemical characterization of glycopeptide antigens.

References

  1. Landsteiner, Karl; Levine, Philip (1927). "Further Observations on Individual Differences of Human Blood". Experimental Biology and Medicine. 24 (9): 941–942. doi:10.3181/00379727-24-3649. S2CID   88119106.
  2. 1 2 3 Kaczmarek, Radoslaw; Buczkowska, Anna; Mikolajewicz, Katarzyna; Krotkiewski, Hubert; Czerwinski, Marcin (2014). "P1PK, GLOB, and FORS blood group systems and GLOB collection: biochemical and clinical aspects. Do we understand it all yet?" . Transfusion Medicine Reviews. 28 (3): 126–136. doi:10.1016/j.tmrv.2014.04.007. PMID   24895151.
  3. 1 2 Hellberg, Åsa Hellberg (2020). "P1PK: a blood group system with an identity crisis" . ISBT Science Series. 15: 40–45. doi:10.1111/voxs.12505. S2CID   201971613.
  4. Szymczak-Kulus, Katarzyna; Weidler, Sascha; Bereznicka, Anna; Mikolajczyk, Krzysztof; Kaczmarek, Radoslaw; Bednarz, Bartosz; Zhang, Tao; Urbaniak, Anna; Olczak, Mariusz; Park, Enoch Y.; Majorczyk, Edyta (January 2021). "Human Gb3/CD77 synthase produces P1 glycotope-capped N-glycans, which mediate Shiga toxin 1 but not Shiga toxin 2 cell entry". Journal of Biological Chemistry. 296: 100299. doi: 10.1016/j.jbc.2021.100299 . ISSN   0021-9258. PMC   7949097 . PMID   33460651.
  5. Kaczmarek, Radoslaw; Duk, Maria; Szymczak, Katarzyna; Korchagina, Elena; Tyborowska, Jolanta; Mikolajczyk, Krzysztof; Bovin, Nicolai; Szewczyk, Boguslaw; Jaskiewicz, Ewa; Czerwinski, Marcin (2016-01-29). "Human Gb3/CD77 synthase reveals specificity toward two or four different acceptors depending on amino acid at position 211, creating Pk, P1 and NOR blood group antigens" . Biochemical and Biophysical Research Communications. 470 (1): 168–174. doi:10.1016/j.bbrc.2016.01.017. ISSN   0006-291X. PMID   26773500.
  6. 1 2 3 4 5 6 Roback JD et al. AABB Technical Manual, 16th Ed. Bethesda: AABB Press, 2008.
  7. Cooling LW, Walker KE, Gille T, Koerner TAW. Shiga Toxin Binds Human Platelets Via Globotriaoslyceramide (Pk antigen) and a Novel Platelet Glycosphingolipid. Infect Immun 1998; 66: 4355-66.
  8. Beadling W, Cooling L. Immunohematology. In: McPherson RA, Pincus MR, eds. Henry's Clinical Diagnosis and Management by Laboratory Methods. 25th Ed. Philadelphia: Saunders, 2007: 618-68.
  9. "dbSNP: the NCBI database of genetic variation" . Retrieved 2020-08-18.
  10. Yeh, Chih‐Chun; Chang, Ching‐Jin; Twu, Yuh‐Ching; Hung, Shu‐Ting; Tsai, Yi‐Jui; Liao, Jia‐Ching; Huang, Ji‐Ting; Kao, Yu‐Hsin; Lin, Sheng‐Wei; Yu, Lung‐Chih (2018). "The differential expression of the blood group P1‐A4GALT and P2‐A4GALT alleles is stimulated by the transcription factor early growth response 1". Transfusion. 58 (4): 1054–1064. doi:10.1111/trf.14515. PMID   29399809. S2CID   4730839.
  11. Westman, Julia S.; Stenfelt, Linn; Vidovic, Karina; Möller, Mattias; Hellberg, Åsa; Kjellström, Sven (2018). "Allele-selective RUNX1 binding regulates P1 blood group status by transcriptional control of A4GALT". Blood. 131 (14): 1811–1818. doi: 10.1182/blood-2017-08-803080 . PMID   29438961.
  12. "rs397514502 RefSNP Report - dbSNP - NCBI". www.ncbi.nlm.nih.gov.
  13. Duk, Maria; Reinhold, Bruce B; Reinhold, Vernon N; Kusnierz-Alejska, Grazyna; Lisowska, Elwira (2001). "Structure of a neutral glycosphingolipid recognized by human antibodies in polyagglutinable erythrocytes from the rare NOR phenotype". Journal of Biological Chemistry. 276 (44): 40574–40582. doi: 10.1074/jbc.M102711200 . PMID   11504714.
  14. Suchanowska, Anna; Kaczmarek, Radoslaw; Duk, Maria; Lukasiewicz, Jolanta; Smolarek, Dorota; Majorczyk, Edyta; Jaskiewicz, Ewa; Laskowska, Anna; Wasniowska, Kazimiera; Lisowska, Elwira; Czerwinski, Marcin (2012). "A single point mutation in the gene encoding Gb3/CD77 synthase causes a rare inherited polyagglutination syndrome". Journal of Biological Chemistry. 287 (45): 38220–38230. doi: 10.1074/jbc.M112.408286 . PMC   3488091 . PMID   22965229.
  15. Smith D, Aye T, Er LS, Nester T, Delaney M (2019). "Acute Hemolytic Transfusion Reaction due to Anti-P1: A Case Report and Review of Institutional Experience". Transfus Med Hemother. 46 (5): 380–383. doi:10.1159/000490897. PMC   6876609 . PMID   31832064.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  16. Duk, Maria; Kusnierz-Alejska, Grazyna; Korchagina, Elena Y; Bovin, Nicolai B; Bochenek, Stanislawa; Lisowska, Elwira (2005). "Anti-α-galactosyl antibodies recognizing epitopes terminating with α1,4-linked galactose: human natural and mouse monoclonal anti-NOR and anti-P1 antibodies". Glycobiology. 15 (2): 109–118. doi: 10.1093/oxfordjournals.glycob.a034964 . PMID   15342552.
  17. Mais DD. ASCP Quick Compendium of Clinical Pathology, 2nd Ed. Chicago: ASCP Press, 2009.