The human leukocyte antigens and their relationship to infection

Human leukocyte antigen DR (HLA-DR) expression on peripheral blood monocytes has been found to correlate highly with infection in many clinical scenarios. This is particularly true for the trauma patient, where changes in HLA-DR expression predate and therefore often predict development of infection. Expression of this antigen is limited to immunocompetent cells, such as B lymphocytes, macrophages, and activated T cells. The HLA-DR heterodimer is required for major histocompatibility complex restricted antigen presentation, a key step in the development of a specific immune response. The degree of monocyte HLA-DR expression may reflect the ability eventually to present antigen, since close correlation has been found between the two. There was remarkable reproducibility of monocyte HLA-DR expression among > 100 asymptomatic volunteers without regard to age, gender, race, and sampling time. Immunosuppressive medication had no effect. Incubation of monocytes from severely infected patients with endotoxin distinguished survivors from those who died by enhanced HLA-DR expression in the survivors. Of several agents that enhance HLA-DR expression, interferon-gamma has received the most attention in experimental models as well as humans. Although promising in selected patients, further clinical trials will be needed to define its specific role. Identification of the patient at high risk for infection, particularly following trauma, will be crucial for the efficient evaluation of future therapeutic interventions. Monocyte HLA-DR expression is the first simple assessment of the host immune response to play an important role in this endeavor.