余家利2006-07-262018-07-092006-07-262018-07-092005-05-27http://ntur.lib.ntu.edu.tw//handle/246246/23785Objective. Immune hyporesponsiveness of mononuclear cell (MNC) and polymorphonuclear neutrophils (PMN) predisposes patients with active systemic lupus erythematosus (SLE) susceptible to infections. This study aimed to explore the pathogenetic factors for it. Methods. Sixty-three patients in total fulfilling the 1982 revised ACR classification criteria for SLE and the same number of sex- and age-matched normal individuals were studied. Reduction-oxidation (redox) capacity [glutathione (GSH) level, GSH peroxidase (GSH-Px) and GSH reductase (GSSG-R) activities], mitochondrial (mt) functions (mitochondrial potential, mitochondrial mass, ATP production and mtDNA 4977bp deletion), and activation-related parameters (membrane potential changes and expression of Na+ and K+-associated molecules) of MNC and PMN were compared in normal and SLE groups. In addition, the effects of anti-dsDNA autoantibodies (100IU/ml) purified from active SLE sera on GSH-Px activity and apoptosis was determined. Results: The GSH level and GSH-Px activity in SLE-MNC and GSH level in SLE-PMN are lower than the normal counterparts. The reduced redox capacity in SLE immune cells seems not relevant to the anti-SLE medications because the same tendency was also observed in 8 untreated Active SLE patients. The reciprocal expression of GSH-Px isomers in MNC and PMN was the same in normal and SLE patients in that dimer (50kDa) and tetramer (100kDa) are prominent in MNC whereas monomer (25kDa) and trimer (75kDa) are prominent in PMN. The defective redox capacity in SLE immune cells leads to 3 impaired mitochondrial functions with defective ATP production, decreased mitochondrial mass, reduced mitochondrial potentials, and increased mtDNA 4977bp deletion (18.2% in SLE vs. 4.3% in normal). The membrane potential of SLE-MNC and PMN was also diminished due to decreased expression of Na+-K+-ATPase, epithelial Na+ channel and renal outer medullary K+ channel. Anti-dsDNA antibodies (25-100IU/ml) purified from SLE sera suppressed GSH-Px activity and increasing normal cells apoptosis. Conclusion. Reduced redox capacity, and defective Na+ and K+ transport-related molecule expression are the predisposing factors for immune hyporesponsiveness in patients with active SLE. Anti-dsDNA autoantibodies play a role on reducing redox capacity in these patients.application/pdf147883 bytesapplication/pdfzh-TW國立臺灣大學醫學院分子醫學研究所systemic lupus erythematosusimmune hyporesponsivenessredox capacitymitochondrial functionNa+ and K+ transportersjournal articlehttp://ntur.lib.ntu.edu.tw/bitstream/246246/23785/1/932314B002085.pdf