Blood groups and diseases associated with inherited abnormalities of the red blood cell membrane

Abstract

HE UNIQUE design of the red blood cell (RBC), and of the RBC membrane that encapsulates hemoglobin within it, ensures that the RBC is able to accomplish the major function of transporting respiratory gases throughout the body. The RBC membrane is thus a flexible, deformable, semifluid slructure that allows the cell passage through small capillaries. Because there are no internal Olganelles to repair damage in the mature RBC, the membrane must be resilient. These unique mechanical properties are attributable to a meshwork of membrane skeleton proteins that interacts with the lipid bilayer through the integral membrane proteins, some of which carry blood group antigens (Fig 1). The blood group antigens are inherited, polymorphlc, structural characteristics, defined by specific amino acid sequences on proteins or by carbohydrates attached to either proteins or lipids. More than 250 blood group antigens have been described and placed into 25 blood group systems. 1 The study of individuals who have a null phenotype for a certain blood group system and thus have RBCs that lack or have altered membrane protein(s) has provided a key to the function of that protein. For example, RBCs with the rare Rhnull phenotype were found to lack several proteins. That these proteins have a role in maintaining RBC morphology and integrity is indicated by the finding that Rhnull RBCs have stomatocytic morphology and reduced in vivo survival. In recent years, the characterization of the molecular genetics of most of the 25 blood group systems, combined with the study of null phenotypes, has expanded our understanding of the structure and function of the membrane components carrying blood group antigens. The functions attributed to, or proposed for, these membrane components are diverse and include