Presence of interferon and anti-interferon in patients with systemic lupus erythematosus

Abstract

Sera from 61 patients with systemic lupus erythematosus (SLE) were serially screened over a period of at least 2 years for IFN and anti-IFN antibodies. IFN concentrations were measured both with a cytopathic effect assay and a more sensitive radioimmunoassay. Of the patients 15% (9/61) had IFN in their serum at one or more occasions as measured in the bioassay (greater than or equal to 6 IU/ml); employing a RIA (greater than or equal to 1 IU/ml) 28% (17/61) of the patients studied were positive for IFN-alpha. Fifteen patients had a measurable interferonemia over 2-16 months; only two patients had detectable IFN in their serum at only one occasion. In five patients, hourly and daily variations of the IFN titer as measured by RIA were found to amount to less than 80%. The IFN activity found in these sera was characterized as IFN-alpha by means of acid stability, cross-reactivity on heterologous cells, trypsin sensitivity, and neutralization by homologous and heterologous antisera. IFN antibodies were quantified with a neutralization bioassay, an ELISA, and a radioimmunoassay. Of the 61 patients 5% (3) possessed high titers of anti-IFN antibodies which persisted over 2 years. The IFN-alpha antibody positive patients had an inactive form of the disease over years without visceral involvement but decreased serum complement levels (C4, C3, CH50) and repeated episodes of Quincke-like edema.

Analysis of gene expression profiles in human systemic lupus erythematosus using oligonucleotide microarray

“…Therefore, we suspect that such false-negative results were due to the relatively low sensitivity of the oligonucleotide microarray method, resulting in a bias of the array data toward abundant transcripts. 18 Of the many differentially expressed genes found in our study, changes in protein expression levels have been previously reported including IFN-o, 19 OAS series enzymes, 20,21 ADPRT, 22 and TCR a. 23 A noteworthy finding in our study, is the interferon pathway.…”

“…25 Later, IFN-o was found in the sera of SLE, and it may also be a major IFN species produced by peripheral blood cells in SLE patients. 19,20,[26][27][28] In naturally occurring SLE, both circulating IFN-a and increased levels of IFN-a-inducible proteins, such as OAS1, OAS2, and OASL, have been reported. [19][20][21] Because long-term IFN-a therapy of patients with nonautoimmune disorders can induce antinuclear antibodies, antibodies to native DNA and also Fold-change Figure 2 Verification of microarray quantification.…”

“…19,20,[26][27][28] In naturally occurring SLE, both circulating IFN-a and increased levels of IFN-a-inducible proteins, such as OAS1, OAS2, and OASL, have been reported. [19][20][21] Because long-term IFN-a therapy of patients with nonautoimmune disorders can induce antinuclear antibodies, antibodies to native DNA and also Fold-change Figure 2 Verification of microarray quantification. Relative mRNA levels (Fold-change y-axis) of the indicated genes Ly6E, OAS2, and CEBPD were measured using the TaqMan 5'nuclease fluorigenic quantitative PCR assay (left column) in same samples (x-axis) as those used to prepare probes for the microarray hybridizations (right column).…”

Elevated levels of endogenous apoptotic DNA and IFN‐α in complement C4‐deficient mice: Implications for induction of systemic lupus erythematosus

“…IFN-a is another important factor in the development of SLE, and elevated levels of this antiviral cytokine or IFN-a-induced genes are frequently observed in patients with SLE [12][13][14][15]. Activation of the class I IFN system has been confirmed by recent studies using microarray approaches [16][17][18][19].…”

“…Current explanations for the loss of tolerance in states of complement deficiency include impaired elimination of apoptotic bodies [4,5] or dying cells [6] as a source of autoantigens [7,8], and inadequate regulation of follicular B cells via the complement receptor CD21/35 [3], although the absence of CD21, or its most important ligand (C3d), does not seem to be associated with SLE [9,10]. As such, neither model alone can adequately account for the association of complement deficiency and SLE [11].IFN-a is another important factor in the development of SLE, and elevated levels of this antiviral cytokine or IFN-a-induced genes are frequently observed in patients with SLE [12][13][14][15]. Activation of the class I IFN system has been confirmed by recent studies using microarray approaches [16][17][18][19].…”