The Concept of Compatibility: Towards a Functional Understanding of Immunohematology

A variety of strategies has been developed to assure safety of hemotherapy. Such strategies aim in particular at avoiding transfusion-transmitted infections. Safety of hemotherapy requires – in addition to safety of transfusion from infections – tolerance of the recipient towards the blood component to be transfused and tolerance of the blood component to be transfused towards the recipient, i.e. compatibility of recipient and blood component. Diagnostic strategies in immunohematology contribute significantly to safety strategies in the field of hemotherapy. However, immunohematology contributes to transfusion safety much more than diagnostic strategies. It contributes a conceptual understanding of compatibility, underlying diagnostic strategies. Immunohematology defines compatibility at the basis of structure, i.e. compatibility is dependent on structural components of single cells, single antibodies, and their interaction. Currently available techniques derived from the spectrum of biochemistry, biophysics and molecular biology allow structural components of cells, antibodies, cell-cell interactions and cell-antibody interactions to be determined at a much higher degree of resolution than ever before. Typing of alleles underlying the expression of different HLA antigens and typing of alleles underlying the expression of different forms of the Rhesus protein D (Rh(D)) exemplarily demonstrate the potential of high-resolution techniques in immunohematology to determine specificity – and thereby also compatibility, according to the understanding of compatibility in today’s immunohematology – at the basis of structure. In contrast to immunohematology, transfusion medicine provides a different understanding of compatibility. Transfusion medicine defines compatibility not primarily at the basis of structure, but at the basis of function, i.e. at the basis of the outcome of an immune response in the setting of hemotherapy, cell therapy, or organ transplantation. Immune interactions relevant to the outcome of immune responses in transfusion and transplantation medicine occur in the context of a highly complex and dynamic biological system that is characterized by plasticity under functional aspects. Under these conditions, structure does not necessarily predict function. Thus, albumin attenuates the activation of neutrophil granulocytes induced by antibodies against neutrophil-specific antigens [1]; challenge of healthy individuals negative for the antigen Rh(D) with red blood cells expressing the highly immunogenic protein Rh(D) results in about 20% of individuals that do not respond to the allogeneic stimulus [2, 3]; and antibodies passively administered together with their specific antigen may enhance or suppress antibody responses, depending on antibody isotype, antigen size and solubility, and the repertoire of Fcγ receptors expressed by the recipient [4]. The concept of compatibility in today’s immunohematology does not sufficiently consider that specificity – and thereby compatibility – may be defined by functional aspects of the immune system in its respective condition as much as by structural components of immune cells and immune receptors. A concept of compatibility in immunohematology that takes into account functional aspects of the immune response requires the understanding of regulatory mechanisms that determine the proper recognition of ‘self ’and ‘non-self’ blood cell antigens in the context of complex dynamic interactions at the cellular and humoral level of the immune system. The reviews compiled in the present issue of TRANSFUSION MEDICINE AND HEMOTHERAPY, completing a series of reviews initiated in the preceding issue, focus on the understanding of immune interactions contributing to the outcome of immune responses and may be of relevance to a definition of compatibility that considers both structural and functional aspects of the immune response to blood cells. In the first review, Fredrick G. Karnell and John G. Monroe, USA, summarize the role of membrane lipids for the regulation of immune cell activity: Lipid rafts are plasma membrane