Patients with systemic lupus erythematosus (SLE) have a circulating inducer of interferon-alpha (IFN-alpha) production acting on leucocytes resembling immature dendritic cells - PubMed (original) (raw)

Patients with systemic lupus erythematosus (SLE) have a circulating inducer of interferon-alpha (IFN-alpha) production acting on leucocytes resembling immature dendritic cells

H Vallin et al. Clin Exp Immunol. 1999 Jan.

Abstract

Patients with active SLE often have an ongoing production of IFN-alpha. We therefore searched for an endogenous IFN-alpha-inducing factor (IIF) in SLE patients and found that their sera frequently induced production of IFN-alpha in cultures of peripheral blood mononuclear cells (PBMC) from healthy blood donors, especially when the PBMC were costimulated with the cytokines IFN-alpha2b and granulocyte-macrophage colony-stimulating factor (GM-CSF). The phenotype of the IFN-alpha-producing cells (IPC) as determined by flow cytometry corresponded to that of the natural IPC, resembling immature dendritic cells. The IIF activity in SLE sera was sometimes as high as that of a virus and was present especially in patients with active disease and with measurable IFN-alpha levels in serum. The IIF had an apparent molecular weight of 300-1000 kD and appeared to consist of both immunoglobulin and DNA, possibly being immune complexes. This endogenous IFN-alpha inducer may be of pathogenic significance, since a reported occasional adverse effect of IFN-alpha therapy in patients with non-autoimmune disorders is development of anti-dsDNA antibodies and SLE.

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Figures

Fig. 1

Fig. 1

IFN-α production of normal peripheral blood mononuclear cells (PBMC) (previously frozen) in response to stimulation by sera (20%) from SLE patients (SLE; n = 34), or healthy controls (ctrl; n = 18). The PBMC cultures were either supplemented (+) or not (–) with 500 U/ml of IFN-α2b and 1 ng/ml granulocyte-macrophage colony-stimulating factor (GM-CSF). Levels of produced IFN-α were determined by a specific immunoassay, not detecting the added IFN-α2b. The median IFN-α production occurring in cytokine-supplemented cultures without serum was 1 U/ml (range < 1–4 U/ml) and < 1 U/ml in unsupplemented cultures. Results from one of four representative PBMC donors with similar results. See Patients, Materials and Methods for further details.

Fig. 2

Fig. 2

Infrequent but strongly IFN-α mRNA-positive peripheral blood mononuclear cells (PBMC) detected by in situ hybridization. The PBMC were stimulated by 20% of an SLE serum (donor C and serum 3 in Table 3) for 5 h, fixed and processed for in situ hybridization as described in Patients, Materials and Methods. (Mag. × 400.)

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