Apoptosis in patients with primary antiphospholipid antibody syndrome

Int J Rheum Dis. 2019 Apr;22(4):677-685. doi: 10.1111/1756-185X.13468. Epub 2019 Feb 6.

Abstract

Aim: Dysregulated apoptosis has been implicated in autoimmune diseases. In the present study, we investigated the apoptosis-related cytokines and apoptosis in patients with primary antiphospholipid syndrome (pAPS).

Method: We prospectively recruited 12 pAPS patients, 17 antiphospholipid antibody (APA)-positive systemic lupus erythematosus (SLE) patients without APS manifestations (APA+ SLE), 13 SLE patients with secondary APS (APS+ SLE) and 10 healthy controls (HCs). Plasma levels of soluble apoptosis-inducing ligands and cytokines, and the expression levels of apoptosis-inducing ligands in peripheral blood mononuclear cells, were determined. In addition, blood lymphocytes/monocytes apoptosis were determined in six pAPS patients and six HCs, using flow cytometric analysis of caspase 3, 8 and 9 activities.

Results: There was a trend toward higher plasma levels of soluble tumor necrosis factor (TNF)-related apoptosis-inducing ligand (sTRAIL), interleukin-10 (IL-10) and TNF-α in pAPS patients when compared with HCs. We also observed higher plasma levels of IL-10 and TNF α in APA+ SLE and APS+ SLE patients when compared with HCs. However, there was no significant difference in blood lymphocytes/monocytes apoptosis between pAPS patients and HCs.

Conclusion: There was a trend toward elevated plasma levels of sTRAIL, IL-10 and TNF-α, but no evidence for dysregulated apoptosis in pAPS patients.

Keywords: Fas ligand; antiphospholipid antibody syndrome; apoptosis; caspase; systemic lupus erythematosus; tumor necrosis factor-like weak inducer of apoptosis; tumor necrosis factor-related apoptosis-inducing ligand.

MeSH terms

  • Adult
  • Antiphospholipid Syndrome / blood
  • Antiphospholipid Syndrome / genetics
  • Antiphospholipid Syndrome / immunology
  • Antiphospholipid Syndrome / pathology*
  • Apoptosis Regulatory Proteins / blood*
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis*
  • Biomarkers / blood
  • Case-Control Studies
  • Cytokines / blood*
  • Female
  • Humans
  • Interleukin-10 / blood
  • Lymphocytes / immunology
  • Lymphocytes / metabolism
  • Lymphocytes / pathology*
  • Male
  • Middle Aged
  • Monocytes / immunology
  • Monocytes / metabolism
  • Monocytes / pathology*
  • Prospective Studies
  • TNF-Related Apoptosis-Inducing Ligand / blood
  • Tumor Necrosis Factor-alpha / blood

Substances

  • Apoptosis Regulatory Proteins
  • Biomarkers
  • Cytokines
  • IL10 protein, human
  • TNF-Related Apoptosis-Inducing Ligand
  • TNFSF10 protein, human
  • Tumor Necrosis Factor-alpha
  • Interleukin-10