Leflunomide-induced peripheral neuropathy: rapid resolution with cholestyramine wash-out

Abstract

To analyse the expression of receptor activator of NF-kappaB (RANK) and RANK ligand (RANKL) in the joints of children with juvenile idiopathic arthritis (JIA), to characterize the phenotype of RANK(+) cells and to test the hypothesis that some RANK(+) cells are of the dendritic type. Paired samples of peripheral blood mononuclear cells (PBMC) and synovial fluid mononuclear cells (SFMC) from children with oligoarticular (n=14) or polyarticular (n=4) JIA and PBMC from 10 control subjects were studied for expression of RANK, RANKL and dendritic cell-specific ICAM (intercellular adhesion molecule)-grabbing non-integrin (DC-SIGN) by the reverse transcriptase-polymerase chain reaction and three-colour flow cytometry. Expression of DC-SIGN and RANK was followed after 1 week of culture with granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin 4 (IL-4). mRNA for RANK was detected in both adherent cells and T cells from PBMC and SFMC of patients with JIA and in control PBMC, while mRNA for RANKL was detectable in the T-cell fraction from JIA patients but not in that from controls. By flow cytometry, a large number of RANK(+) cells were detected in the joint; these cells had the phenotype HLA-DR(hi)CD86(hi) CD11c(+) and expressed low levels of DC-SIGN. There is increased expression of RANKL and RANK in the juvenile arthritic joint. RANK is expressed on a population of cells with features of dendritic cells. RANK/RANKL interactions may contribute to the survival of inflammatory cells within the joint, as well as to erosions and osteoporosis in juvenile arthritis.