Patients with systemic lupus erythematosus have reduced numbers of circulating natural interferon-alpha- producing cells

J Autoimmun. 1998 Oct;11(5):465-70. doi: 10.1006/jaut.1998.0215.

Abstract

Systemic lupus erythematosus (SLE) patients often have continuous production of interferon-alpha (IFN-alpha), but production of in vitro IFN-alpha by peripheral blood mononuclear cells (PBMC) may be varyingly reduced. We here report that IFN-alpha production induced by Herpes simplex virus (HSV) in PBMC resembling immature dendritic cells and designated natural IFN-alpha producing cells (NIPC), was much more affected than that induced by sendai virus (SV) in monocytes. At the cell level, the frequency of HSV-activated NIPC was reduced 70-fold, but residual NIPC produced normal amounts of IFN-alpha (1-2 U/cell). The NIPC frequency increased 10-fold in SLE-PBMC, but not in control PBMC, when co-stimulated by the combination IFN-alpha-gamma and GM- CSF. No spontaneous IFN-alpha production by PBMCs was detected in SLE patients. While no SLE serum factor inhibiting IFN-alpha production was seen, sera of four out of 11 SLE patients induced IFN-alpha production in healthy control PBMC. We propose that the number of NIPC in SLE are reduced in blood because of recruitment to tissues and activation by an endogenous IFN-alpha inducer, as well as because of lack of co-stimulatory cytokines. IFN-alpha produced in SLE could be of pathogenic significance, because autoimmune diseases develop in patients with infections or tumours during IFN-alpha therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Autoantibodies / blood
  • Case-Control Studies
  • Dendritic Cells / immunology
  • Female
  • Humans
  • In Vitro Techniques
  • Interferon-alpha / biosynthesis*
  • Interferon-alpha / blood
  • Leukocytes, Mononuclear / immunology*
  • Lupus Erythematosus, Systemic / blood
  • Lupus Erythematosus, Systemic / etiology
  • Lupus Erythematosus, Systemic / immunology*
  • Male
  • Middle Aged
  • Organ Specificity
  • Respirovirus / immunology
  • Simplexvirus / immunology

Substances

  • Autoantibodies
  • Interferon-alpha