Reduced perforin expression in systemic juvenile idiopathic arthritis is restored by autologous stem-cell transplantation

Objectives. Familial haemophagocytic lymphohistiocytosis (FHL) is a disorder characterized by deficient cytotoxic T-cell function and activated macrophages, owing to a defect in the perforin gene and absent perforin expression. Because symptoms of patients with systemic juvenile idiopathic arthritis (sJIA) are sometimes clinically very similar to those with FHL, we studied whether perforin expression in sJIA patients would be reduced also. Methods. We determined the perforin expression levels on two subsets of CD8(+) cells (CD8(+)CD28(-)CD45RA(-) and CD8(+)CD28(-)CD45RA(+)) and natural killer (NK) cells from patients with sJIA under conventional treatment as well as before and after autologous stem-cell transplantation (ASCT). Results. CD45RA(-) cytotoxic effector cells of sJIA patients (n=13) express significantly lower levels of perforin than polyarticular juvenile idiopathic arthritis (pJIA, n = 9) patients [sJIA mean fluorescence intensity (MFI) 34.6; pJIA MFI 98.0] or control donors (MFI 124.6, n = 5). A similar pattern was seen in the CD45RA(+) subset. Also NK cells from sJIA patients expressed significantly less intracellular perforin (sJIA MFI 398.4; controls MFI 972.4). In four patients with sJIA who were treated with ASCT, A clear increase in perforin expression was found at 12 months after ASCT in both cytotoxic effector cell subsets (CD45RA(-) subset before ASCT MFI 13.2; 12 months after ASCT MFI 172.3). Conclusion. We conclude that perforin expression can be severely reduced in sJIA. This finding may implicate defective cytotoxicity and haemophagocytosis and could thus explain why sJIA may be complicated by macrophage activation syndrome. ASCT leads to a reconstitution of the (T cell) immune system with a normal expression of perforin.