Deoxyribonuclease-inhibitory antibodies in systemic lupus erythematosus.
Deoxyribonucleases (DNases) are key enzymes for digesting DNA. Abnormalities in the function of these enzymes may contribute to the development of anti-DNA antibodies in systemic lupus erythematosus (SLE). In this study, we used bovine DNase 1-coated ELISA plates to screen anti-DNase antibodies in SLE patients. About 62% of the sera of SLE patients (63/101) were positive for anti-DNase antibodies compared to only 8% of normal controls (8/98). A positive correlation was also found between the concentrations of anti-DNase and anti-DNA antibodies in sera of SLE patients. Affinity-purified anti-DNase immunoglobulin G (IgG) from pooled sera of SLE patients bound to bovine DNase as well as DNA. A synthetic peptide, corresponding to the catalytic site of DNase, was able to completely inhibit the binding of anti-DNase IgG to DNase. In addition to bovine DNase, the anti-DNase IgG also bound to and inhibited the enzymatic activities of DNase present in streptococcal supernatants and human urine. Immunization of lupus-prone NZB/NZW mice with bovine DNase enhanced the production of anti-DNase and DNA antibodies, and accelerated the occurrence of proteinuria. Taken together, these results suggest that DNase-inhibitory antibodies which recognize a conserved epitope near the catalytic site of DNase may act in the pathogenesis of SLE.
Yeh
Trai-Ming
TM
Department of Medical Technology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC. today@mail.ncku.edu.tw
Chang
Hung-Chuan
HC
Liang
Chun-Ching
CC
Wu
Jiunn-Jong
JJ
Liu
Ming-Fei
MF
D000818:Animals; D000974:Antibodies, Antinuclear / Q000494:pharmacology*; D002417:Cattle; D003850:Deoxyribonuclease I / Q000037:antagonists & inhibitors; D003851:Deoxyribonucleases / Q000037:antagonists & inhibitors* / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007700:Kinetics; D008180:Lupus Erythematosus, Systemic / Q000201:enzymology / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D011507:Proteinuria / Q000276:immunology; D012016:Reference Values; D013297:Streptococcus pyogenes / Q000302:isolation & purification; D014556:Urine / Q000382:microbiology
D000974:Antibodies, Antinuclear; D003851:Deoxyribonucleases; D003850:Deoxyribonuclease I