Expanding role of circulating adhesion molecules in assessing prognosis and treatment response in human immunodeficiency virus infection.

To patrol the body effectively and to generate an immune response to infectious organisms, the effector cells of the immune system must be able to congregate in lymphoid organs, to migrate to inflammatory tissues by crossing endothelial and basement membrane barriers, and to adhere to cells bearing foreign antigens. These actions are mediated by a number of surface accessory molecules, the adhesion molecules, which bind to specific counter-receptors expressed on endothelial cells, other cells of the immune system, and/or extracellular matrix components (60, 82). Moreover, adhesion molecules transduce activating signals for T-helper, T-cytotoxic, and B cells (42) and are involved in their differentiation, proliferation, antigen recognition, migration and trafficking, cytokine production, and apoptosis (13, 76, 82). Adhesion molecules are classified into three families: the selectins, the integrins, and the immunoglobulin superfamily (60, 82). Expression of adhesion molecules on the surfaces of immune cells is widely induced by cytokines released during immune activation; therefore, aberrant expression has been described in various diseases characterized by immune activation, including autoimmune, malignant, and infectious diseases (29, 74). Proteolytic cleavage of several membrane-bound adhesion molecules results in the release of soluble isoforms into circulation. Although there is some evidence that circulating adhesion molecules (CAMs) interfere with various cell-cell interactions and may act as signal transducers, their possible biological role still remains unclear. Circulating adhesion molecules have been found in the sera of healthy individuals, and increased levels have been described in various immune-mediated diseases (29). Numerous studies, summarized in Table 1, have shown that human immunodeficiency virus (HIV) infection is associated with abnormalities in the synthesis and expression of various adhesion molecules. Consequently, abnormal levels of circulating isoforms have been reported in HIV-infected patients (29, 52). Although numerical and functional decline of CD4 T cells is a major feature, the immunodeficiency associated with HIV infection is a much more complex process involving several pathogenic mechanisms mediated by adhesion molecules, such as altered function, distribution, and migration of lymphocytes and dysfunction of neutrophils (58). The aim of this review is to summarize the available data on the aberrations of the levels of certain CAMs in HIV-infected patients, as well as on their biological significance, their prognostic value regarding the course of the disease, and their potential role in assessing the efficacy of highly active antiretroviral treatment (HAART).