Observations on Blood Factors RhA, Rhα, RhB, and Rhc

Unger, Lester J.; Wiener, Alexander S.; Katz, Lillian; Delayo, R.; Derose, M.; Stever, M.

doi:10.1093/ajcp/31.2.95

Cited by 26 publications

(7 citation statements)

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“…Numerous similar cases were recorded with different mutual reactivities of their anti‐Ds and their RBCs. Different descriptions were used to classify these cases: Wiener and Unger used ‘components Rh A–D , Tippet and Race ‘categories I‐VII’ . A revolution in differentiation of these phenotypes came with the introduction of monoclonal anti‐Ds into serological diagnostics.…”

Section: Challenges With Dna Rescuementioning

confidence: 99%

After 70 years, serological RhD determination remains a challenge: DNA to the rescue

Pı́sačka

2018

ISBT Science Series

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After ABO system antigens, RhD is the most clinically significant blood group antigen. This is reflected in its high immunogenicity and potential to cause haemolytic transfusion reactions (HTR) and severe haemolytic disease of the newborn (HDN). Thus, correct determination of the RhD antigen is essential for a safe transfusion strategy and adequate indications of anti‐D immunoglobulin prophylactic administration. The RhD determination challenge started in 1939 with a case history of fatal HDN and HTR in a mother who was transfused with her husband′s blood. Subsequent findings of an antibody reacting with 80% ABO compatible red blood cells (RBCs) in the serum of the afflicted woman lead to the hypothesis that the mother was lacking an antigen present on the father's and fetal RBCs and that her production of a corresponding antibody was responsible for both HDN and HTR. This hypothesis was proven to be correct. The following year, the effort to determine the origin of a causal antigen coincided with an animal immunization experiment where a similarly reacting antibody developed by injecting Rhesus monkey RBCs into rabbits and guinea‐pigs, as well as with another publication of HTRs after ABO compatible blood transfusions in patients with antibodies of apparently identical specificity. This first challenge in the ‘pre‐DNA’ era was slightly erroneously named in humans as the anti‐Rhesus antibody, and 20 years later, the animal antibody was designated anti‐LW. Meanwhile, the complexity of Rh group of antigens increased and several genetic models were suggested to explain it: Rh‐Hr single gene, three genes C, D and E and finally a two locus model (which a few years later was shown by molecular analysis to be the accurate one). At the beginning, serological determination of RhD was performed using human anti‐D, first by direct agglutination (IgM), later also using the Coombs’ test (IgG). Weak D antigens were a challenge at the time: the term ‘DU’ (now obsolete) was used for those antigens negative in direct agglutination and positive in the Coombs’ test. Weakening of the D antigen could be caused indirectly by the ‘position effect C in Trans’ or directly (mutations in the RHD gene, usually point mutations coding for amino acids in transmembranous and intracellular parts of the polypeptide). Extremely weakened D antigens are called Del, and these are serologically detected only by adsorption/elution tests (multiple genetic mechanisms). The next challenge came in the 1960s, with the observation of qualitative D variants – partial D antigens. The first cases were detected after the development of allo‐anti‐D in D‐positive individuals – immunized against that part of the D protein missing in their D epitope mosaic. Mutual reactivity of anti‐D from these individuals with different partial D antigens established the basis for their classification. The increase in partial D types accelerated dramatically after the development of the mouse hybridoma technique and the production of numerous different monoclonal anti‐Ds. Accordin...

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Section: Challenges With Dna Rescuementioning

confidence: 99%

After 70 years, serological RhD determination remains a challenge: DNA to the rescue

Pı́sačka

2018

ISBT Science Series

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“…The subject was investigated by Unger and Wiener [2] who, in 1959, named the component parts recog nized at that time as RhA, RhB, Rhc and RhD. An alterna tive approach has been the classification of D-positive indi viduals who have made anti-D into seven categories, name ly, I-VII [3,4]; the original category I has now been abandoned and categories III, IV and V have been sub divided [3].…”

Section: Introductionmentioning

confidence: 99%

Demonstration of Seven Epitopes on the Rh Antigen D Using Human Monoclonal Anti-D Antibodies and Red Cells from D Categories

Lomas¹,

Tippett²,

Thompson³

et al. 1989

Vox Sanguinis

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The agglutination patterns have been established for the reaction between 29 monoclonal antibodies with specificity for the Rh antigen D and red cells of D categories IIIa, IIIc, IVa, IVb, Va, Vc, VI and VII, which are known to lack certain epitopes on the D polypeptide. Six different agglutination patterns were recognized and interpreted to indicate the recognition of seven different epitopes. These epitopes are termed epD1 through to epD7. The separate existence of epD6 and epD7 is deduced from previous observations in inhibition studies using purified 125 I-labelled antibodies; they cannot yet be distinguished in agglutination tests. The number of epitopes lacking from cells of each category varied between two and five. As all the antibodies agglutinated cells of categories IIIa, IIIc and VII and cells of categories II, IIIb and Vb were not available, it is probable that there are epitopes other than the seven presently recognized. Eighteen out of the 29 antibodies which were examined recognized epitopes epD6/7 and it is suggested either that antibodies recognizing these epitopes predominate in polyclonal anti-D sera, or that the lymphocytes producing these antibodies are preferentially selected during establishment of cell lines.

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“…

Since 1953, when Argall, Ball and Trentelman [l] reported an example, it has been realized that rare people exist who have the antigen D on their red cells and anti-D in their serum. It was assumed that these people lack some part of the normal D and that they have made antibody t o the missing part.The subject has been studied and reviewed b y Unger and Wiener [8,9,10,11, 121 who name component parts of what we call the D antigen A, B, C and D and indicate missing components by small letters, for example Rhlc, Rh,cd, Rh,b, etc.

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mentioning

confidence: 99%

“…The subject has been studied and reviewed b y Unger and Wiener [8,9,10,11, 121 who name component parts of what we call the D antigen A, B, C and D and indicate missing components by small letters, for example Rhlc, Rh,cd, Rh,b, etc.…”

mentioning

confidence: 99%