Investigation of the caspase-dependent mitochondrial apoptotic pathway in mononuclear cells of patients with systemic Lupus erythematosus

J Transl Med. 2014 Nov 6:12:303. doi: 10.1186/s12967-014-0303-1.

Abstract

Background: This study aimed to explore the role of apoptosis initiators, caspase-9, caspase-10, mitochondrial anti-viral signaling protein (MAVS), and interferon regulatory factor 7 (pIRF7), in patients with systemic lupus erythematosus (SLE).

Methods: Leukocyte apoptosis was determined by flow cytometry, including annexin V, APO2.7, and 7-amino-actinomycin D (7-AAD) on each subtype of leukocyte in 35 patients with SLE, 15 disease controls, and 17 volunteer normal controls. Levels of caspase-9, caspase-10, MAVS, and pIRF7 in mononuclear cells and the disease activity index (SLEDAI) in the SLE patients were determined. Correlation among intracellular adaptor proteins and caspase levels were calculated.

Results: The SLE patients had higher APO2.7 in total leukocyte, lymphocyte, and monocytes, and higher late apoptosis markers in total leukocytes and neutrophils than normal controls (all p < 0.05). Disease activity was positively associated with the APO2.7 of CD19+ cells in SLE, but negatively associated with MAVS and caspase-9 levels (all p < 0.05). Markers of viral infection and anti-virus transcription factors like MDA5, MAVS, and pIRF7 were significantly higher in SLE patients than in disease controls (p < 0.05). Caspase-9 and caspase-10 levels positively correlated with MAVS and pIRF7 in SLE patients (p < 0.05).

Conclusions: The disease activity of SLE is positively associated with APO2.7 level of CD19+ cells but negatively associated with MAVS and caspase-9 levels, which all point to a mitochondrial pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism
  • Adult
  • Apoptosis*
  • Biomarkers / metabolism
  • Case-Control Studies
  • Caspase 10 / metabolism*
  • Caspase 9 / metabolism*
  • Demography
  • Female
  • Humans
  • Leukocytes, Mononuclear / enzymology
  • Leukocytes, Mononuclear / metabolism*
  • Leukocytes, Mononuclear / pathology
  • Lupus Erythematosus, Systemic / enzymology
  • Lupus Erythematosus, Systemic / metabolism*
  • Lupus Erythematosus, Systemic / pathology*
  • Lymphocytes / metabolism
  • Lymphocytes / pathology
  • Male
  • Middle Aged
  • Mitochondria / metabolism*
  • Monocytes / metabolism
  • Monocytes / pathology

Substances

  • Adaptor Proteins, Signal Transducing
  • Biomarkers
  • MAVS protein, human
  • Caspase 10
  • Caspase 9
  • CASP10 protein, human