Likewise, many pathogens can utilize or interact with several different blood group antigens. Some systems, such as ABO, have multiple associations with infectious disease. Other blood groups are associated with membrane microdomains (for example, P k, P, Cromer, GIL, Colton, and Raph) and play a role in endocytosis, cell signaling, and the immune response. Interestingly, many of these same proteins are receptors for intraerythrocytic pathogens (malaria, Bartonella species, and Babesia species), with a loss of red cell deformability upon infection ( 5). Several blood group proteins are clustered at the red cell band 3-ankyrin metabolon (Diego, MNSs, Duffy, Colton, and LW) and junctional complexes (Diego, Gerbich, and MNSs), which anchor the membrane to the underlying cytoskeleton ( 3, 4). Many blood groups reside on proteins critical for red cell maturation and function. As noted in Table 1, blood group antigens may reflect polymorphisms on red cell glycoproteins or are carbohydrate epitopes (ABO and Lewis) on glycoproteins and glycolipids ( 1, 2).

ABO antibodies can be considered part of the innate immune system against some bacterial pathogens and enveloped viruses that carry ABO-active antigens.Īt present, there are 34 blood group systems recognized by the International Society for Blood Transfusion (ISBT) ( 1, 2). Finally, bacteria can stimulate antibodies against blood group antigens, including ABO. Blood groups can also serve as false receptors, preventing binding to target tissue. Many blood groups are receptors for toxins, parasites, and bacteria, where they can facilitate colonization or invasion or evade host clearance mechanisms. Blood groups are frequent targets in epidemiological investigations since they are genetically determined traits with known polymorphic expression among individuals and populations. Since the discovery of the ABO blood group, there has been an ongoing interest in the potential role of blood groups in infectious disease. Finally, there is a symbiotic relationship between blood group expression and maturation of the gastrointestinal microbiome. Microorganisms can also stimulate antibodies against blood group antigens, including ABO, T, and Kell. Several distinct phenotypes associated with increased host resistance to malaria are overrepresented in populations living in areas where malaria is endemic, as a result of evolutionary pressures. Several blood groups can modify the innate immune response to infection. In addition, many blood group antigens facilitate intracellular uptake, signal transduction, or adhesion through the organization of membrane microdomains. Blood groups can play a direct role in infection by serving as receptors and/or coreceptors for microorganisms, parasites, and viruses. Differences in blood group antigen expression can increase or decrease host susceptibility to many infections. At present, there are 34 recognized human blood groups and hundreds of individual blood group antigens and alleles.

Blood group antigens represent polymorphic traits inherited among individuals and populations.

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