Lymphocyte apoptosis and macrophage function: correlation with disease activity in systemic lupus erythematosus

Abstract

Increased lymphocyte apoptosis and defects in macrophage removal of apoptotic cells have been suggested to contribute to the development of systemic lupus erythematosus (SLE). The aim of this study was to investigate the relationship between peripheral lymphocyte apoptosis, macrophage function as determined by the serum levels of neopterin and interferon-gamma (IFN-gamma), and SLE disease activity. Peripheral apoptotic lymphocytes (AL) were detected by annexin V-fluorescein isothiocyanate (FITC) staining and flow cytometry. Serum levels of neopterin and IFN-gamma were measured by enzyme-linked immunosorbent assay (ELISA). SLE disease activity was determined using the systemic lupus activity measure (SLAM) and the serum titer of anti-dsDNA antibodies. The percentage of AL in the peripheral blood of active SLE patients was significantly higher (13.07+/-7.39%, n=30) than that of the inactive SLE patients (4.08+/-3.55%, n=8, p<0.01) and normal controls (5.13+/-3.37%, n=11, p<0.01). Serum levels of neopterin in active SLE patients were significantly higher (1.39+/-1.10 microg/dl, n=22) than in controls (0.26+/-0.19 microg/dl, n=20, p<0.01). Serum levels of IFN-gamma in active SLE patients were elevated (58.97+/-34.52 ng/l, n=15) when compared with controls (28.06+/-2.35 ng/l, n=16, p<0.05). The percentage of AL correlated significantly with serum levels of neopterin (r=0.446, p<0.05, n=22) and SLAM score (r=0.533, p<0.001, n=38), but not with the serum levels of IFN-gamma. The SLAM score also correlated with the serum levels of neopterin (r=0.485, p<0.05, n=22), but not with those of IFN-gamma. Our study supported the hypothesis that increased lymphocyte apoptosis has a pathogenic role in SLE. The increased levels of serum neopterin may suggest an attempt of the patients' macrophage system to remove the apoptotic cell excess. Since serum levels of neopterin correlated with the overall lupus disease activity, they may be regarded as an index of SLE disease activity.