Double-stranded RNA antibodies in systemic lupus erythematosus.

Abstract

Davis, P., Cunnington, P., and Hughes, G. R. V. (1975). Annals ofthe Rheumatic Diseases, 34,239-243. Double-stranded RNA antibodies in systemic lupus erythematosus. Antibodies to viral double-stranded RNA (ds RNA) have been found in 40% ofpatients with systemic lupus erythematosus (SLE) and 14-5 % of patients with rheumatoid arthritis. These antibodies were diagnostically more specific for SLE than those directed against artificial polynucleotides, poly I: C and poly A: U. Although not disease specific, high titres of antibody to ds viral RNA were found almost exclusively in SLE. Serial studies failed to show that RNA antibody levels correlated with disease activity.Although of considerable interest in experimental studies on the pathogenesis of SLE, ds viral RNA antibodies are of little clinical significance in the management of SLE.Systemic lupus erythematosus (SLE) is characterized by a wide variety of circulating antibodies. In particular, antibodies against double-stranded DNA (ds DNA) have been shown to have clinical significance in their diagnostic specificity and sensitivity in SLE (Hughes, 1971;Hughes, Cohen, and Christian, 1971). Ofinterest has been the demonstration in SLE of antibodies directed against double-stranded RNA (ds RNA) (Schur and Monroe, 1969;. This finding, together with the fact that most human RNA is single stranded, has led to the suggestion that these antibodies may be directed against viral antigens (Schur, Stollar, Steinberg, and Talal, 1971).A variety ofmethods has been used in the detection of RNA antibodies, including the sensitive Farr technique (Wold, Young, Tan, and Farr, 1968) and the filter radioimmunoassay technique (Attias, Sylvester, and Talal, 1973). The antigen most widely used in these techniques has been the synthetic polynucleotide poly inosinic:poly cytidylic acid (poly I: C), which has structural and chemical similarities to ds RNA. Using this technique, Schur and his colleagues (1971) detected antibodies against poly I: C in 51 % of SLE sera, but these were not specific, also being found in 9% of patients with rheumatoid arthritis (RA) and in 6 % of normals. In the present study we have substituted the synthetic polynucleotide poly I:C for a highly purified preparation of doublestranded viral RNA obtained from Penicillium cultures, and assessed the frequency and specificity of

Macrophage fumarate hydratase restrains mtRNA-mediated interferon production

“…4o). Autoantibodies to dsRNA, as well as dsDNA, have been detected in patients with SLE 61,62 . However, it is unclear whether FH suppression is a cause or consequence of increased IFN signalling, as Fh1 can also be inhibited by IFNβ stimulation in BMDMs (Extended Data Fig.…”

ZBP1 is a significant pyroptosis regulator for systemic lupus erythematosus

“…Suzuki et al found that phospholipid scramblase (phospholipid scramblase 1) induces fibrin turnover and increases cell-surface phosphatidylserine exposure, promoting the risk of thrombus (25). Doublestranded RNA antibodies have also been investigated in SLE, and RNA antibody levels have been found to be associated with disease activity (28). Interferon has been shown to act as an important regulator of SLE, and interferon lambda affects the immune system and inflammation dysregulation (29).…”

Targeting mitochondrial metabolites and nucleic acids as an anti-inflammatory strategy

“…Reduced FH activity has been shown in several diseases. In Systemic lupus erythematosus (SLE) patients, autoantibodies to double stranded RNA (dsRNA) are observed (Davis et al, 1975). Reduced ADAR1 RNA-editing activity results in dsRNA-mediated interferon response.…”