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Monocytes are resistant to apoptosis in systemic juvenile idiopathic arthritis

Shivani Srivastava1, Claudia Macaubas, Chetan Deshpande

  • 1Department of Biology, Stanford University, Stanford, CA, USA.

Clinical Immunology (Orlando, Fla.)
|May 14, 2010
PubMed

Insights

Monocytes from patients with systemic juvenile idiopathic arthritis (SJIA) resist apoptosis through both extrinsic and intrinsic pathways. Circulating factors in active SJIA may contribute to this resistance, impacting immune cell function.

Area of Science:

  • Immunology
  • Cell Biology
  • Pediatric Rheumatology

Background:

  • Systemic juvenile idiopathic arthritis (SJIA) is a severe form of childhood arthritis.
  • Aberrant immune cell function, including apoptosis resistance, is implicated in autoimmune diseases.
  • The role of monocyte apoptosis in SJIA pathogenesis is not fully understood.

Purpose of the Study:

  • To investigate apoptosis resistance in circulating monocytes from SJIA patients.
  • To identify the specific apoptotic pathways involved in SJIA monocyte resistance.
  • To determine if plasma factors in SJIA contribute to monocyte apoptosis resistance.

Main Methods:

  • Microarray analysis of peripheral blood mononuclear cells (PBMC) from SJIA patients and controls.
  • RT-PCR analysis of isolated monocytes.
  • Assessment of monocyte apoptosis using annexin binding assays and caspase activity.
  • Stimulation of extrinsic (anti-Fas) and intrinsic (staurosporine) apoptotic pathways.
  • Incubation of normal monocytes with SJIA plasma.

Main Results:

  • Monocytes from active SJIA patients express transcripts associated with apoptosis resistance.
  • SJIA monocytes exhibit reduced annexin binding and FasL up-regulation in low serum.
  • SJIA monocytes show decreased susceptibility to anti-Fas-induced apoptosis.
  • Activation of the mitochondrial pathway in SJIA monocytes reveals diminished Bid cleavage and Bcl-w down-regulation.
  • Plasma from SJIA patients reduces the apoptotic response of normal monocytes.

Conclusions:

  • Monocytes from SJIA patients are resistant to apoptosis.
  • This resistance involves alterations in both the extrinsic and intrinsic apoptotic pathways.
  • Circulating factors in active SJIA plasma contribute to monocyte apoptosis resistance, suggesting a broader impact on immune cell homeostasis.

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