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Apoptosis and expression of soluble Fas mRNA in systemic lupus erythematosus

T Papo1, C Parizot, M Ortova

  • 1Internal Medicine department, La Pitié-Salpêtrière Hospital, Paris, France. thomas.papo@psl.ap-hop-paris.fr

Lupus
|October 31, 1998
PubMed

Insights

Systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) show skewed Fas alternative splicing toward soluble Fas mRNA in peripheral blood mononuclear cells (PBMCs). This indicates altered apoptosis regulation in these autoimmune diseases.

Area of Science:

  • Immunology
  • Molecular Biology
  • Autoimmune Diseases

Background:

  • Fas receptor plays a crucial role in apoptosis, a key process in immune system regulation.
  • Dysregulation of apoptosis is implicated in the pathogenesis of autoimmune diseases like SLE and RA.
  • Alternative splicing of Fas mRNA can lead to soluble and membrane-bound forms, potentially affecting immune cell function.

Purpose of the Study:

  • To compare the soluble/membrane Fas mRNA ratio in peripheral blood mononuclear cells (PBMCs) between patients with SLE, rheumatoid arthritis (RA), and healthy controls.
  • To investigate the relationship between Fas splicing, Fas ratio, and lymphocyte apoptosis in SLE.
  • To assess in vitro lymphocyte apoptosis following T cell activation in SLE patients.

Main Methods:

  • Quantitative reverse transcription polymerase chain reaction (RT-PCR) to determine soluble/membrane Fas mRNA ratios in PBMCs.
  • Nick-end labeling and flow cytometry to measure lymphocyte apoptosis in vitro.
  • Analysis of patients with active vs. inactive SLE, and those with vs. without nephritis.

Main Results:

  • The soluble/membrane Fas mRNA ratio was significantly higher in SLE patients compared to healthy subjects (P = 0.0001).
  • Patients with lupus nephritis had a higher Fas ratio than those without nephritis (P=0.039).
  • RA patients also exhibited a higher Fas ratio than healthy subjects (P = 0.0003).
  • In vitro lymphocyte apoptosis after T cell activation was significantly increased in active SLE patients compared to controls.
  • Fas alternative splicing was skewed toward the soluble form in both SLE and RA patients compared to healthy individuals.

Conclusions:

  • Fas alternative splicing is altered in SLE and RA, favoring the soluble form.
  • This altered splicing correlates with increased apoptosis in active SLE patients.
  • The findings suggest a role for aberrant Fas signaling in the pathogenesis of SLE and RA.

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