Objective: Myeloid related proteins (MRP) 8 and 14 and the heterodimer MRP8/14 are myeloid differentiation markers present on infiltrating tissue macrophages in inflammation but not on resident tissue macrophages. We determined the pattern of expression of MRP8, MRP14, and the MRP8/14 heterodimer (27E10 antigen) in rheumatoid arthritis (RA) synovial membrane (SM).
Methods: SM samples were obtained from patients with RA at joint replacement surgery or at arthroscopy and patients without joint disease (healthy subjects) and immunostained for MRP8, MRP14, 27E10 antigen (MRP8/14 heterodimer), and CD68. Positive cell staining was measured by quantitative analysis.
Results: SM from 8 patients with RA, including 7 who had paired samples from both adjacent to the cartilage-pannus junction (CPJ) and an area remote from the CPJ, and 2 healthy controls were analyzed. In RA, CD68+ cells accumulated in greater numbers adjacent to the CPJ than remote from the CPJ [mean +/- standard error of the mean (SEM) 488+/-103 and 286+/-76 cells/mm2, respectively; p = 0.01]. SM lining layer (LL) MRP8, MRP14, and 27E10 staining was observed predominantly adjacent to the CPJ and only in patients with active disease. Minimal or absent LL MRP staining was observed in non-CPJ sections. Synovial sublining layer (SL) MRP8, MRP14, and 27E10 staining was also observed only in patients with active disease, but in contrast to the LL, SL staining was observed predominantly in sections remote from the CPJ.
Conclusion: MRP antigens, representing activation markers on SM macrophages, were observed predominantly in the LL of sections adjacent to the CPJ samples. These original observations suggest altered activation and differentiation of lining layer macrophages at the site of maximal cartilage destruction in RA.