Rh Blood Group System

  • The second major blood grouping system is the Rhesus (Rh) system.
  • Philip Levine, in 1939, discovered that the sera of most women who gave birth to infants with hemolytic disease contained an antibody that reacted with the red cells of the infant and with the red cells of 85% of Caucasians.
  • In 1940, Landsteiner and Wiener injected blood from the monkey Macacus rhesus into rabbits and guinea pigs, and discovered the resulting antibody agglutinated rhesus (Rh) red cells, which appeared to have the same specificity as the neonatal antibody.
  • The donors whose cells were agglutinated by the antibody to Rh red cells were termed Rh positive; those whose cells were not agglutinated were termed Rh negative.
  • It is now known that the antibody obtained by Landsteiner and Wiener reacts with an antigen (LW) is different but is closely related to the one that is recognized in human hemolytic disease, but nevertheless the Rh nomenclature is still retained.
  • Like the ABO blood types, the Rh factor is an inherited blood protein, or antigen, on red blood cells.

Rh Blood Group System

Rh Blood Group Antigens

  • The term Rh blood group system refers to the five main Rh antigens (C, c, D, E, and e) as well as many other less frequent Rh antigens.
  • The terms Rh factor and Rh antigen are similar, and both refer to the RhD antigen only.
  • Of all the Rh antigens, antigen D (RhD) is most important.

Rhesus D hemolytic disease

D-antigen

  • Individuals either have or do not have the RhD antigen on the surface of their red blood cells.
  • This is usually indicated by “RhD positive” (does have the RhD antigen) or “RhD negative” (does not have the antigen) suffix to the ABO blood type.
  • This suffix is often shortened to “D pos”/“D neg,” “RhD pos”/“RhD neg,” or +/-.
  • The latter symbol is generally not preferred in research or medical situations, because it can be altered or obscured accidentally.
  • There are several alloantigenic determinants within the Rh system.
    • Clinically, the D antigen has a lot of medical importance. This is because RhD negative individuals who receive RhD positive erythrocytes by transfusion can develop alloantibodies that may lead to severe reactions with further transfusions of RhD-positive blood.
    • The D antigen also poses a problem in RhD-negative mothers who bear a child with RhD-positive red cells inherited from the father. The entry of fetal erythrocytes into the maternal circulation at parturition or trauma during the pregnancy (such as in amniocentesis) can lead to alloimmunization against the RhD antigen. This may cause hemolytic disease of the newborn in subsequent pregnancies. This can now be prevented by the administration of Rh (D) immunoglobulin to these women within 72 hours of parturition.
  • Unlike the ABO system, there are no natural antibodies against Rh antigens.
  • Antibodies against Rh antigens develop only in certain situations, such as in Rh incompatible pregnancy or transfusion.
  • Most of these antibodies are IgG antibodies and few IgM antibodies.
  • These are incomplete antibodies and can be detected in newborn blood by direct Coombs’ test and in mother blood by indirect Coombs’ test.

Rh Blood Group System

About Author

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Sagar Aryal, PhD

Dr. Sagar Aryal is a microbiologist, researcher, and science communicator from Nepal. He is also co-founder and Research Head of the Department of Natural Products at the Kathmandu Research Institute for Biological Sciences (KRIBS), where he leads research on natural product discovery and microbial biodiversity. Dr. Aryal earned his Ph.D. in Microbiology from Tribhuvan University, Kathmandu, Nepal, in 2025, supported by a DAAD Research Grant and a University Grants Commission (UGC) Nepal Ph.D. Fellowship. His research interests include Actinomycetes, Myxobacteria, microbial taxonomy, and natural products, particularly the discovery of bioactive compounds with potential pharmaceutical applications. He isolated and identified Nocardia nepalensis, a novel bacterial species from Nepal, contributing to understanding microbial diversity in the region. Dr. Aryal has published more than 16 research articles in international journals and contributed three book chapters to established academic publications. He has presented scientific research findings and developed international research collaborations through visits to more than 18 countries across Asia, Europe, North America, and Oceania. From 2023 to 2025, he served as the American Society for Microbiology (ASM) Young Ambassador to Nepal. Since December 2025, he has served as an Editorial Board Member of Scientific Reports, a Nature Portfolio journal. In recognition of his scientific contributions, Dr. Aryal received the NAST Science and Technology Youth Award 2025 from the Nepal Academy of Science and Technology. He previously received the Frs. Locke and Stiller Research Award (LSRA) for the 2017-2018 cycle from St. Xavier's College, Kathmandu, and a Nepal Academy of Science and Technology (NAST) Research Grant for 2017-2018. Alongside his scientific career, Dr. Aryal has more than 15 years of experience in blogging, content writing, and search engine optimization (SEO).