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Dean L. Blood Groups and Red Cell Antigens . Bethesdomain authority (MD): National Center for Biotechnology Information (US); 2005.


The antigens of the Diego blood group are carried on an important protein, called theband 3 protein, which lies in the red blood cell (RBC) membrane. This protein is achloride/bicarbonate exchanger involved in carbon dioxide transport from tissues tolungs. It also is found in the kidney, where it is involved in acid secretion.

Many mutations in the gen that encodes the Diego antigens, SLC4A1, are known. Thesemutations can result in RBCs with an abnormal membrane (hereditary ovalocytosis andspherocytosis) và kidneys that are defective in secreting acid (renal tubuleacidosis). Other SLC4A1 mutations that vị not give rise to disease may result in newblood group antigens that belong khổng lồ the Diego blood group system.

Number of antigens21: Dia, Dib, and Wra areahy vọng the most significant
Antigen specificityProteinAmino acid sequence determines thespecifiđô thị of Diego antigens
Antigen-carrying moleculesGlycoprotein that transports anionsThe Diegoprotein is a transmembrane, multi-pass protein that is integral tothe RBC membrane. It is an anion antiporter that exchangesCl- and HCO3- across the RBC membrane.
Molecular basisThe SLC4A1 gen encodes the Diegoantigens.Located on chromosome 17 (17q21-22), theSLC4A1 gen contains trăng tròn exons that span more than 18 kbp of DNA. Thealleles Dib và Dia result from a SNP(2561C→T), and the corresponding Dib andDia antigens differ by a single amino acid(P854L).
Frequency of Diego antigensDia is found mainly inpopulations of Mongolian descent. It is found in36% of South American Indians, 12% of Japanese, & 12% of Chinese,whereas it is rare in Caucasians and Blacks (0.01%).Dib is found universally in mostpopulations (1).
Frequency of Diego phenotypesDi(a-b+) is found in >99.9%of Caucasians & Blacks và >90% ofAsians.Di(a+b+) found in <0.1% of Caucasians& Blacks và in 10% Asians.Di(a+b-) found in <0.01%Caucasians, Blacks, and Asians.Di(a-b-) found in 1 case only(1).

Antibody toàn thân typeIgG or IgMAnti-Dia andanti-Dib is IgG; anti-Wra is IgG or IgM (1).
Transfusion reactionYesAnti-Dia & anti-Dibare capable of causing a moderate to lớn severe delayed transfusionreaction. Anti-Wra can cause an immediate hemolytictransfusion reaction (1).
Hemolytic disease of the newbornYes Anti-Dia and anti-Wracan cause severe disease. Anti-Dib tends khổng lồ causemild hemolytic disease (1).


The Diego blood group was discovered in 1955 and was named for the first patientto produce an antitoàn thân against the new blood system"s antigens. The patient,Mrs. Diego, had given birth to lớn a child affected by HDoanh Nghiệp. Her serum was found tocontain an antitoàn thân (now called anti-Dia) which, during herpregnancy, had crossed the placenta lớn attachồng the RBCs of her fetus (whichexpressed the Dia antigen).

In 1967, a second Diego antigen, Dib, was discovered. It wasn"t until1995 that other Diego antigens began to be discovered.

At present, 21 Diego antigens are known, but it is the presence or absence ofDia và Dib that is of importance in determining aperson"s Diego blood type.

Note: The alternate gen symbol is AE1, which stands for Anion Exchanger 1. Thealternate gene name is erythrocyte membrane protein b& 3.

Common phenotypes

The most comtháng Diego phenotype is Di(a-b+), which is found in over 99.9%Caucasians and Blacks, và over 90% of Asians. The Di(a+b+) is found in 10% ofAsians. Whereas the Dia antiren is universally expressed in mostpopulations, the prevalence of the Dia antigene differs among muốn races,making the Diego blood group of great interest khổng lồ anthropologists (3).

In the USA, the Dia antigene has not been found in Caucasian or Blackblood donors (4). TheDia antigene is more commonly found in Oriental people of Mongoliandescent, being more comtháng in the Japanese (12%) & the Chinese (5%). In SouthAmerican Indians, up khổng lồ 54% of the population carries the Dia antigen(1).

Interestingly, the Dia antigen is less rare in the Polish population(0.47%) (5) compared lớn mostCaucasian populations (0.01%). This may reflect the gene admixture that resultedfrom the invasion of Pol& by Tatars (Mongolian heritage) many centuries ago(6).

Expression of Diego antigens

The expression of Diego antigens is limited to lớn RBCs and the kidney (in the distaltubule and the collecting tubule).

Anion exchange across the RBC membrane

The SLCA41 protein is an anti-porter that plays an essential role in enablingthe RBC to transport the waste product CO2 lớn the lungs, where itcan be removed from the body toàn thân.

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The SLCA41 protein exchanges one Cl- for one HCO3-. Thedirection of the exchange depends on the concentration of the ions on eitherside of the RBC membrane. When levels of waste CO2 are high,CO2 diffuses across the RBC membrane và is converted intoHCO3- which is transported out of the RBC in exchange forCl-. If anion exchange did not occur, HCO3- wouldaccumulate inside the RBC and reach toxic levels, altering the intracellularpH. In the lungs, the lower cấp độ of CO2 encourages the directionof the exchange lớn reverse. Once inside the RBC, the HCO3- yieldsCO2 which diffuses out of the RBC & is exhaled from thebody toàn thân.

Integral protein of the RBC membrane

The SLCA1 protein is an integral part of the RBC membrane. It helps anchorthe membrane lớn the underlying spectrin skeleton. It helps the RBC khổng lồ bestable and flexible, & maintain its biconcave shape.

Mutations of SLC4A1 can cause abnormally shaped RBCs that may be spherical(spherocytes, seen in hereditary spherocytosis), oval shaped (ovalocytes,seen in Southeast Asian ovalocytosis), or elliptical (elliptocytes). Becausethese RBCs are more fragile, they are prematurely removed from thecirculation (hemolytic anemia).

Anion exchange across in the kidney tubule

SCLA1 is expressed in the kidney, where it also mediates the exchange ofanions. Mutations that disrupt its function can cause a renal tubularacidosis in which the kidney fails khổng lồ adequately excrete acid anions,allowing them to lớn accumulate.

Transfusion reactions

Anti-Dia và anti-Dib are more commonly associated with HDNthan transfusion reactions. However, these antibodies are capable of causingimmediate (9) & delayedhemolytic transfusion reactions (2,8).

Hemolytic disease of the newborn

HDoanh Nghiệp caused by Diego antibodies are more comtháng in South East Asia và SouthAmerica.

Anti-Dia is capable of causing moderate khổng lồ severe HDoanh Nghiệp, and cases havebeen reported in Japan (9),Đài Loan Trung Quốc (10, 11), và Poland(5).

Anti-Dib typically causes mild HDoanh Nghiệp. Cases have been reported in Japan(12), Trung Quốc (13), Pol& (6), and in a mother of SouthAmerican descent (14).


The SLC4A1 ren, also known as the AE1 ren, is a thành viên of the anionexchanger (AE) ren family. SLC4A1 is located on chromosome 17q21-q22 andconsists of đôi mươi exons that are distributed over almost 18 kbp of genomic DNA.

The Dia và Dib antigens are produced as a result of asingle nucleotide polymorphism (SNP) of the SLC4A1 gen. The result is at aminoacid position 854; the comtháng (wild-type) Dib antigen has a prolineresidue, & the Dia antigen has a leucine residue.


The b& 3 protein encoded by SLC4A1 is an important integral protein of the RBCmembrane. It is 911 amino acids in length, and it loops across the RBC membrane12 times.

The N terminal domain name of the protein lies in the cytoplasm of the RBC, where itinteracts with hemoglobin (influencing the exchange of anions) and alsointeracts with metabolic enzymes (influencing the metabolism of glucose insidethe RBC).

Its C-terminal domain spans across the membrane of the RBC & mediates theexchange of chloride và bicarbonate anions across the membrane.

Reid ME & Lomas-Francis C. The Blood GroupAntigen Facts Book. Second ed. 2004, New York: Elsevier AcademicPress..
Daniels G L , Fletcher A . et al. Blood group terminology 2004: from the International Societyof Blood Transfusion committee on terminology for red cell surfaceantigens. Vox Sang. 2004;87(4):304–316.
Daniels G. Human Blood Groups, Second ed. 2002,Blackwell Science.

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Komatsu F , Hasegawa K , Yanagisawa Y , Kawabata T , Kaneko Y , Watanabe S , Miyagi S , Sakuma M , Kagawa Y , Kajiwara M . Prevalence of diego blood group Dia antigene in Mongolians:comparison with that in Japanese. Transfus Apheresis Sci. 2004;30:119–24.
Kusnierz-Alejska G , Bochenek S . Haemolytic disease of the newborn due to anti-Dia andincidence of the Dia antiren in Poland. Vox Sang. 1992;62:124–6.
Lenkiewicz B , Zupanska B . The first example of anti-Diego(b) found in a Polish womanwith the Di(a+b-) phenotype and haemolytic disease of the newborn notrequiring treatment. Transfus Med. 2003;13:161–3.
Hinckley M E , Huestis D W . Case report. An immediate hemolytic transfusion reactionapparently caused by anti-Dia. Rev Fr Transfus Immunohematol. 1979;22:581–5.
Yamane K , Yagihashi A , Sasaki M , Kuwashima K , Morio A , Watanabe N . A delayed hemolytic transfusion reaction (DHTR) with multiplealloantibodies (Anti-E, Jka, Dia, Fyb, and S) induced byE-antigen-negative sầu, crossmatch-compatible blood. Immunopharmacol Immunotoxicol. 1998;20:531–9.
Alves de Lima L M , Berthier M E , Sad W E , DiNapoli J , Johnson C L , Marsh W L . Characterization of an anti-Dia antibody toàn thân causing hemolyticdisease in a newborn infant. Transfusion. 1982;22:246–7.
Ting J Y , Ma E S , Wong K Y . A case of severe haemolytic disease of the newborn due toanti-Di(a) antitoàn thân. Hong Kong Med J. 2004;10:347–9.
Yung C H , Lin J S , Hu H Y , Lyou J Y , Chen Y R , Chen C R , Hao T C , Peng C S , Tzeng C H . Zhonghua Min Guo Wei Sheng Wu Ji Mian Yi Xue Za Zhi. 1995;28:146–50.
Uchikawa M , Shibata Y , Tohyama H , Mori H , Aisaka K , Nakagawa M . A case of hemolytic disease of the newborn due lớn anti-Dibantibodies. Vox Sang. 1982;42:91–2.
Chen C C , Broadberry R E , Chang F C , Ding F , Lin M . Hemolytic disease of the newborn caused by maternal anti-Dib:a case report in Taiwan. Zhonghua Yi Xue Za Zhi (Taipei). 1993;52:262–4.
Donato E , Guinot M , Vilar C , Garcia R , Canigral G . rHuEPO in the management of pregnancy complicated by anti-Dib. Transfusion. 2003;43:681–2.

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