Review: other blood group systems—Diego, Yt, Xg, Scianna, Dombrock, Colton, Landsteiner- Wiener, and Indian K.M. B YRNE AND P.C. B YRNE Introduction Diego Blood Group System This review was prepared to provide a basic The Diego blood group system (ISBT: DI/010) has overview of “Other Blood Groups.” Some of the more expanded from its humble beginnings to now include major blood group systems, i.e., ABO, Rh, Kell, Duffy, up to 21 discrete antigens (Table 1). 3 Band 3, an anion and Kidd, are also reviewed in this issue and are not exchange, multi-pass membrane glycoprotein, is the covered here. The sheer mass of data on the MNS basic structure that carries the Diego system antigenic blood group system is so extensive and complicated determinants. 4 The gene that encodes the Band 3 that it justifies a review all of its own, and it is therefore protein is named SLC4A1 and its chromosomal location not discussed in this article. However, various aspects is 17q12–q21. 4 of MNS were described in recent papers in Di a and Di b are antithetical, resulting from a single Immunohematology. 1,2 nucleotide substitution (2561T>C) that gives rise to The blood group systems that are covered are those amino acid changes in the Band 3 protein (Leu854Pro). that most workers believe to have some degree of To date, the Di(a–b–) phenotype has not been clinical importance or interesting features: Diego (DI), described. The Di a and Di b antigens are resistant to Yt (YT), Xg (XG), Scianna (SC), Dombrock (DO), Colton treatment with the following enzymes/chemicals: (CO), Landsteiner-Wiener (LW), and Indian (IN). ficin/papain, trypsin, α-chymotrypsin, DTT (0.2 M), and Readers will find a brief digest of each blood group chloroquine. 4 The only other pair of antithetical system, which includes some historical, statistical, antigens in the system are Wr a and Wr b, the result of genetic, biochemical, and serologic data. It was the another nucleotide substitution (1972A>G) that authors’ intention to compile data that could be produces another change in Band 3 (Lys658Glu). 4 The entitled: “Other Blood Groups: What you need to know extremely rare Wr(a–b–) phenotype has been found in for the SBB exam.” 1 persons with rare glycophorin variants, where Readers will note that there are only a few expression of the Wr b antigen is dependent upon the references used in this review. Most of the information presence of functional glycophorin A. 5 The Wr a and given here has been dissected from the books listed in Wr b antigens are resistant to treatment with the the fourth and fifth references. Between them, they following enzymes/chemicals: ficin/papain, trypsin, α- contain a much more detailed, extensive, and chymotrypsin, DTT (0.2 M), and chloroquine. 4 comprehensive review of the vast volume of material The other antigens in this system are of extremely available on these blood group systems. For additional low frequency and are usually the result of single information or clarification, readers are strongly nucleotide substitutions. Interestingly, many of the encouraged to consult the aforementioned antibodies directed against these low-frequency publications. The additional references contain antigens show some degree of crossreactivity or other pertinent newer information that has been reported serologic associations with each other, and this is often since the publication of the main sources of data. the reason why their inclusion in this blood group 50 IMMUNOHEMATOLOGY, VOLUME 20, NUMBER 1, 2004 Review: less well-known blood group systems Table 1. Diego blood group antigens and/or cause in vitro hemolysis. a First Incidence (%) 5 Anti-Di has often been implicated in ISBT Conventional Historical reported 5 (Caucasians) Notes 4,5 HDN, but reports of immediate DI1 Di a Diego 1955 <0.1 S. Amer. Ind.: 36% Chinese: 5% hemolytic transfusion reactions are Japanese: 12% confused by other issues. 5 Anti-Di b Chippewa: 11% usually only cause mild HDN but DI2 Di b Luebano 1967 >99.9 there have been a few reports of DI3 Wr a Wright 1953 <0.1 delayed transfusion reactions. 4,5 DI4 Wr b Fritz 1971 >99.9 Anti-Wr a is probably one of the DI5 Wd a Waldner 1981 <0.1 Found in two most commonly seen antibodies to a Hutterite families low-frequency antigen (and is a a DI6 Rb Redelberger 1978 <0.1 particular bane to one of the authors DI7 WARR Warrior 1991 <0.1 May be unique to Native Americans during the manufacture of blood grouping reagents). It is often found DI8 ELO 1993 <0.1 in the sera of individuals who have DI9 Wu Wulfsberg 1976 <0.1 produced antibodies to other RBC DI10 Bp a Bishop 1966 <0.1 antigens. Given the extremely low DI11 Mo a Moen 1972 <0.1 frequency of the Wr a antigen it seems a DI12 Hg Hughes 1983 <0.1 unlikely that those individuals have a DI13 Vg Van Vugt 1981 <0.1 been actually exposed to Wr(a+) a DI14 Sw Swann 1959 <0.1 RBCs. DI15 BOW 1988 <0.1 Thus, many examples of anti-Wr a DI16 NFLD Newfoundland 1984 <0.1 appear to be “naturally occurring” or DI17 Jn a 1967 <0.1 stimulated by some-thing other than DI18 KREP 1997 <0.1 RBCs and, in particular, in sera from DI19 Tr a Traversu 1975 <0.1 (Provisional)* individuals who have made multiple DI20 Fr a Froese 1978 <0.1 antibodies to low-frequency DI21 SW1 1987 <0.1 antigens. Behavior of the antibodies * ISBT assignment to DI varies greatly, perhaps dependent upon the method of immunization. system was initially postulated. Most of these low- Many examples of anti-Wr a are IgM, saline-reactive; frequency Diego system antigens have only been found others are IgG, reactive by antiglobulin techniques. Still in small kindreds or isolated ethnic groups. While other examples contain both IgG and IgM these antigens and their corresponding antibodies may components. Most do not bind complement or cause have clinical significance, they have little or no impact in vitro hemolysis. Anti-Wr a has often been implicated upon everyday transfusion medicine. 4 in HDN and transfusion reactions. 5 An altered form of Band 3 protein has been associated with a hereditary form of red cell ovalocytosis known as South East Asian ovalocytosis, Yt Blood Group System and may confer a degree of resistance to invasion by The Yt blood group system (ISBT: YT/011), often the malarial parasite Plasmodium falciparum. A incorrectly referred to as the Cartwright system, complete absence of Band 3, and, therefore, the consists of two antigens: Yt a and Yt b.6 The antigens are Di(a–b–) phenotype, was thought to be incompatible carried by a GPI-linked glycoprotein named acetyl- with life. However, a severely hydropic, anemic baby cholinesterase (AChE), which is the product of the who lacked Band 3 and protein 4.2 was resuscitated ACHE gene located on chromosome 7 at position q22. after birth and kept alive by blood transfusions. 4 The function of this enzyme in RBCs is not known, Antibodies to Di a and Di b are generally IgG1 and however AChE is a major component of nerve impulse IgG3, although some IgM examples have been transmission. 4 reported. 5 They are usually produced in response to The genetic polymorphisms that give rise to the RBC exposure and are reactive by antiglobulin antithetical Yt a and Yt b antigens are the result of a techniques. Rare examples may bind complement nucleotide substitution in ACHE (1057C>A), which IMMUNOHEMATOLOGY, VOLUME 20, NUMBER 1, 2004 51 K.M. B YRNE AND P.C. B YRNE produces an amino acid change in the AChE example of anti-Yt a was reported to bind complement, glycoprotein (His353Asn). 4 As seen in Table 2, Yt a is of but neither in vitro hemolysis nor HDN has been high frequency in Caucasians and Yt b is of moderately attributed to Yt antibodies. 4,5 low frequency. This pattern has been seen in most The clinical significance of Yt antibodies in the populations studied, although the rarity of anti-Yt b has transfusion arena has attracted a great deal of attention limited the volume of screening possible. 4,5 Studies in and has caused an even greater amount of conster- Japan indicate thatYt a may be of higher frequency, since nation. Most work has been done on examples of no Yt(a–) individuals were detected in tests on 5000 anti-Yt a, since examples of anti-Yt b are so rare. Over a donors, and no Yt(b+) samples were found among the dozen studies have been performed on a varying 70 tested with anti-Yt b.5 On the other hand, Yt b appears number of examples of antibody, using a variety of to be more prevalent in Israel, where it was found in 24 clinical significance indicators: 51 Cr survival studies, to 26 percent of individuals tested. This finding was monocyte-monolayer assay (MMA), transfusion of accompanied by a relative lowering of the incidence of antigen-positive cells, and/or combinations of the Yt a. The incidence of the rare Yt(a–b+) phenotype in above. The conclusion: Many examples are benign, i.e., Israel was estimated to be 1 in 65, compared to an not clinically significant. However, other examples estimated 1 in 500 in the United States. 5 have caused shortened RBC survival of transfused antigen-positive cells and Table 2. Yt blood group antigens at least one has caused a delayed 5 First Incidence (%) hemolytic transfusion reaction.