Chronic antigen-specific immune-system activation may potentially be involved in the loosening of cemented acetabular components

Previous studies have attempted to determine whether aseptic loosening and osteolysis are caused by a T cell-mediated type IV hypersensitivity reactio n or a nonspecific foreign body reaction involving phagocytic macrophages. The purpose of this study was to examine the role of the B7-CD28 costimulat ory pathway (which is indicative of an activated immune response) in loosen ing and osteolysis of total joint replacements (TJRs). We harvested peripro sthetic tissues from 24 loose, cemented, all polyethylene, acetabular compo nents in patients undergoing revision total hip replacement surgery for ase ptic loosening. Prostheses were classified radiographically as to whether b allooning, scalloping osteolysis was present or not. Monoclonal antibodies were used to identify macrophages, antigen presenting cells (APCs) expressi ng B7-1 or B7-2, total T lymphocytes, and T cells expressing CD28 or CTLA-4 . The large numbers of positive cells, including macrophages, T cells, and APCs in both groups are substantially higher than previously reported. Macr ophages constituted the predominant cell type, the majority of which were A PCs. B7-1 was expressed by 18.3% of all cells, and B7-2 was expressed by 61 .0% of cells. Despite the fact that there were no statistically significant differences in expression of proteins in the B7-CD28 pathway between the o steolytic and nonosteolytic groups, the magnitude of positive staining sugg ests that the process of aseptic loosening (not osteolysis) may involve pro teins of the B7-CD28 pathway, particularly B7-2. One possible antigenic sti mulus is protein-coated particulate wear debris from prosthetic materials. (C) 2001 John Wiley & Sons, Inc.