Abstract
Anti-double strand DNA antibodies (anti-dsDNA) involve in lupus nephritis. However, their role in tissue damage mechanism remains unclear. In this study, a 45-kDa cognate antigen of anti-dsDNA monoclonal antibodies 9D7 was identified by two-dimensional gel electrophoresis and determined to be human phosphoglycerate kinase 1 (PGK-1) by MALDI-TOF analysis. The binding of 9D7 to PGK-1 was not affected by DNase I but was inhibited by thymus dsDNA. Human SLE sera with high anti-dsDNA titers had a high affinity with PGK. In activated Jurkat T cells, 9D7 decreased the PGK-1 mRNA production and IL-2 promoter activity. Reduction in IL-2 gene expression and protein production were observed in the 9D7-treated cells. Because PGK-1 deficiency may cause mental tardy and hemolytic anemia, interaction between anti-dsDNA and PGK-1 may be important in lupus pathogenesis. Moreover, reduction in IL-2 production by anti-dsDNA suggests their role in increasing infection rate and decreasing proper generation of activation-induced cell death.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Alkaline Phosphatase / metabolism
-
Animals
-
Antibodies, Antinuclear / immunology
-
Antibodies, Monoclonal / immunology
-
Antibodies, Monoclonal / pharmacology*
-
Cross Reactions
-
Cytokines / genetics
-
DNA / immunology*
-
Enzyme-Linked Immunosorbent Assay
-
Humans
-
Interleukin-2 / antagonists & inhibitors*
-
Interleukin-2 / biosynthesis
-
Interleukin-2 / genetics
-
Interleukin-2 / immunology
-
Jurkat Cells
-
Lupus Erythematosus, Systemic / blood
-
Lupus Erythematosus, Systemic / genetics
-
Lupus Erythematosus, Systemic / immunology*
-
Lupus Erythematosus, Systemic / metabolism
-
Mice
-
Phosphoglycerate Kinase / genetics
-
Phosphoglycerate Kinase / immunology
-
Phosphoglycerate Kinase / metabolism*
-
Promoter Regions, Genetic
-
RNA, Messenger / biosynthesis
-
RNA, Messenger / genetics
-
Reverse Transcriptase Polymerase Chain Reaction
-
T-Lymphocytes / drug effects
-
T-Lymphocytes / enzymology
-
T-Lymphocytes / immunology*
-
Transcription, Genetic
Substances
-
Antibodies, Antinuclear
-
Antibodies, Monoclonal
-
Cytokines
-
Interleukin-2
-
RNA, Messenger
-
DNA
-
Phosphoglycerate Kinase
-
Alkaline Phosphatase