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  • DD DD D D DD DD D DD D D D

    DD D

    D DD D D DD DD D DD D D D

    DD D

    D DD D D DD DD D DD D D D

    DD D

    DD DD D D DD DD D DD D D D

    DD

    ImmunohematologyJ O U R N A L O F B L O O D G R O U P S E R O L O G Y A N D E D U C A T I O N

    V O L U M E 2 1 , N U M B E R 4 , 2 0 0 5

    D DD D D DD D DD D DD D D DD D

  • ImmunohematologyJ O U R N A L O F B L O O D G R O U P S E R O L O G Y A N D E D U C A T I O N

    V O L U M E 2 1 , N U M B E R 4 , 2 0 0 5

    C O N T E N T S

    141Review: the Rh blood group system: an historical calendar

    P.D. ISSITT

    146Reactivity of FDA-approved anti-D reagents with partial D red blood cells

    W.J. JUDD, M. MOULDS,AND G. SCHLANSER

    149Case report: immune anti-D stimulated by transfusion of fresh frozen plasma

    M. CONNOLLY,W.N. ERBER,AND D.E. GREY

    152Incidence of weak D in blood donors typed as D positive by the Olympus PK 7200

    C.M. JENKINS, S.T. JOHNSON, D.B. BELLISSIMO,AND J.L. GOTTSCHALL

    155Review: the Rh blood group D antigen . . . dominant, diverse, and difficult

    C.M.WESTHOFF

    164C O M M U N I C A T I O N S

    Letters from the editorsOrtho-Clinical Diagnostics sponsorship

    Thank you to contributors to the 2005 issues

    166 168Letters from the outgoing editor-in-chief Letter from the incoming editorial staff

    Thank you with special thanks to DeloresChanging of the guard

    169I N M E M O R I A M

    John Maxwell Bowman, MD; Professor Sir John V. Davies, MD;Tibor J.Greenwalt, MD;and Professor J.J.Van Loghem

    174 176 177A N N O U N C E M E N T S U P C O M I N G M E E T I N G S A D V E R T I S E M E N T S

    180I N S T R U C T I O N S F O R A U T H O R S

    181I N D E X V O L U M E 2 1 , N O S . 1 , 2 , 3 , 4 , 2 0 0 5

  • EDITOR-IN-CHIEF MANAGING EDITORDelores Mallory, MT(ASCP)SBB Cynthia Flickinger, MT(ASCP)SBB

    Supply, North Carolina Philadelphia, Pennsylvania

    TECHNICAL EDITOR SENIOR MEDICAL EDITORChristine Lomas-Francis, MSc Scott Murphy, MD

    New York, New York Philadelphia, Pennsylvania

    ASSOCIATE MEDICAL EDITORSGeralyn Meny, MD David Moolton, MD Ralph Vassallo, MD

    Philadelphia, Pennsylvania Philadelphia, Pennsylvania Philadelphia, Pennsylvania

    EDITORIAL BOARD

    EDITORIAL ASSISTANT PRODUCTION ASSISTANTJudith Abrams Marge Manigly

    COPY EDITOR ELECTRONIC PUBLISHERLucy Oppenheim Paul Duquette

    Immunohematology is published quarterly (March, June, September, and December) by the American Red Cross, National Headquarters,Washington, DC 20006.

    Immunohematology is indexed and included in Index Medicus and MEDLINE on the MEDLARS system.The contents are also cited in the EBASE/Excerpta Medica and Elsevier BIOBASE/Current Awareness

    in Biological Sciences (CABS) databases.

    The subscription price is $30.00 (U.S.) and $35.00 (foreign) per year.

    Subscriptions, Change of Address, and Extra Copies:Immunohematology, P.O. Box 40325

    Philadelphia, PA 19106Or call (215) 451-4902

    Web site: www.redcross.org/pubs/immuno

    Copyright 2005 by The American National Red CrossISSN 0894-203X

    Patricia Arndt, MT(ASCP)SBBPomona, California

    James P.AuBuchon, MDLebanon, New Hampshire

    Geoffrey Daniels, PhDBristol, United Kingdom

    Richard Davey, MDWashington, District of Columbia

    Sandra Ellisor, MS, MT(ASCP)SBBAnaheim, California

    George Garratty, PhD, FRCPathPomona, California

    Brenda J. Grossman, MDSt. Louis, Missouri

    W. John Judd, FIBMS, MIBiolAnn Arbor, Michigan

    Christine Lomas-Francis, MScNew York, New York

    Gary Moroff, PhDRockville, Maryland

    Ruth Mougey, MT(ASCP)SBBCarrollton, Kentucky

    John J. Moulds, MT(ASCP)SBBShreveport, Louisiana

    Marilyn K. Moulds, MT(ASCP)SBBHouston, Texas

    Sandra Nance, MS, MT(ASCP)SBBPhiladelphia, Pennsylvania

    Paul M. Ness, MDBaltimore, Maryland

    Mark Popovsky, MDBraintree, Massachusetts

    Marion E. Reid, PhD, FIBMSNew York, New York

    Susan Rolih, MS, MT(ASCP)SBBCincinnati, Ohio

    S. Gerald Sandler, MDWashington, District of Columbia

    David F. Stroncek, MDBethesda, Maryland

    Marilyn J.Telen, MDDurham, North Carolina

    Connie M.Westhoff, SBB, PhDPhiladelphia, Pennsylvania

  • Early StudiesThe question as to who discovered the Rh blood

    group system has been vigorously debated for manyyears. In 1939, Levine and Stetson correctly describedthe etiology of a case of HDN. They did not give a nameto the causative antibody in the serum of Mary Seno;had they done so Rh might now have a different name.In 1940, Landsteiner and Wiener described antibodiesproduced in guinea pigs and rabbits that had beeninjected with RBCs from rhesus monkeys. Thepredominant antibody was subsequently shownapparently to have the same specificity as the causativeantibody in the case of HDN described by Levine andStetson. For the rest of their lives Levine and Wienereach claimed that he had discovered the Rh systemindependently of the other. Different terminologieswere used to describe the first and later discovered butclosely related antigens and both Levine and Wienerhad supporters of their claims.

    At one time it was suggested that the system hadbeen discovered earlier. In 1933,Buchbinder publishedresults from studies using animal sera. Rosenfieldpointed out that Buchbinder was a graduate studentworking in Landsteiners laboratory and suggested thatsome of the antibodies foreshadowed the specificitiesreported by Landsteiner and Wiener in 1940 and 1941.However, from his reading of the results published byBuchbinder, this author concluded that all the findingscould be explained by the species differences betweenthe animal sera and the human test RBCs.

    Some early findings about Rh were difficult toexplain. Fisk and Foord reported that while humancord RBCs could be divided into positive and negativeusing human anti-Rh, they all reacted with guinea piganti-Rh. Murray and Clark found that human RBCs,divided into positive and negative with human anti-Rh,all adsorbed guinea pig anti-Rh. Similarly it was claimedthat both Rh+ and Rh RBCs stimulated production ofanti-Rh in animals. In 1961, Levine et al. reported thathuman and animal anti-Rh have different specificities.

    The guinea pig anti-Rh was renamed anti-LW,supposedly in honor of Landsteiner and Wiener. Itfollowed, of course, that if the antibodies raised inguinea pigs and rabbits following immunization withrhesus monkey RBCs had anti-LW specificity, thenLevine and Stetson had discovered Rh in tests on theserum of Mary Seno. Wiener, of course, rejected such aclaim and maintained that the sera of the immunizedrabbits and guinea pigs contained both what had beencalled human anti-Rh and animal anti-Rh. Anti-LWclosely resembles human anti-Rh because the LWantigen is more strongly expressed on Rh+ than on RhRBCs from human adults.

    The fact that the initial experiments of Landsteinerand Wiener used RBCs from rhesus monkeys as theimmunizing source led to many workers calling thesubsequently discovered complex polymorphism theRhesus blood group system. This author was as guiltyas any and even published a book using that name in itstitle. In fact the correct name is the Rh system; themistake of calling it the Rhesus system was never madeby Race and Sanger, who did much of the early pioneerwork on the polymorphism, nor by Mollison, who didmuch to establish the clinical significance of thesystem.

    Up to this point the term anti-Rh has been usedand the terms anti-D and anti-Rh0 have beenstudiously avoided. This is because two distinctterminologies for Rh were used early and it is difficultto interpret one group of workers results in the othersterminology. As discussed in a later section, theterminology schism stemmed from different theoriesregarding the genetic control of Rh antigenproduction. Suffice it here to say that the initial studieson Rh were done with an antibody named anti-Rh0 byWiener and his colleagues and anti-D by Fisher andRace. Levine and his colleagues elected to use thename anti-D. For the rest of this review the Fisher-Race(CDE) terminology will be used (initially Wieners Rh-Hr terms will be listed parenthetically) where names

    I M M U N O H E M A T O L O G Y, V O L U M E 2 1 , N U M B E R 4 , 2 0 0 5 141

    Review: the Rh blood groupsystem: an historical calendarP.D. ISSITT

  • exist. For later findings, where no CDE terms havebeen applied, the numerical terminology of Rosenfieldet al., or the local names applied by the reportingauthors, will be used.

    Early Expansion: the First Five AntigensIt was not long after the discovery of anti-D (anti-

    Rh0) that it became apparent that the situation is farmore complex than a one-antigen, one-antibodysystem. In 1941,Wiener et al.described an antigen nowknown as C (rh). It was noticed that most RBCs thatcarry C are D+. In the same year Levine et al.describedc (hr), an antigen found often on D+ RBCs and almostalways on those that are D. In 1943, Race et al. andWiener and Sonn reported the discovery of an antigenE (rh). It was seen that E was often present on D+RBCs, particularly those that were D+, C. E wasseldom found on D RBCs. At this point Fisherpostulated that C and c have an antitheticalrelationship that is independent of D and E and thatantithetical partners to D and E would eventually berecognized. In 1945, Mourant et al. reported discoveryof e (hr), the anticipated antithetical partner to E. Noverifiable discovery of an antigen antithetical to D wasever reported and eventually the term d came to beused simply to indicate the absence of D. It was almosthalf a century later that biochemical and geneticevidence was produced to show that indeed mostoften when the D gene is absent there is no allelic geneto replace it. Indeed d and d truly indicate the

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