Unsolved mystery of Fas: mononuclear cells may have trouble dying in patients with Sjögren's syndrome

BMC Immunol. 2023 Jun 23;24(1):12. doi: 10.1186/s12865-023-00544-5.

Abstract

Background: Patients with Sjögren's syndrome, like other patients with autoimmune disorders, display dysregulation in the function of their immune system. Fas and Fas Ligand (FasL) are among the dysregulated proteins.

Methods: We studied Fas and FasL on IL-2Rα+ cells and in serum of patients with Sjögren's syndrome (n = 16) and healthy individuals (n = 16); both from same ethnic and geographical background. We used flow cytometry and enzyme-linked immunosorbent for this purpose. We also measured the expression of Bcl-2 and Bax by reverse transcription quantitative real-time PCR (RT-qPCR) and percentage of apoptotic and dead cells using Annexin V and 7-AAD staining in lymphocytes.

Results: FasL was increased in patients' T and B cells while Fas was increased in patients' monocytes, T and B cells. No signs of increased apoptosis were found. sFas and sFasL in patients' serum were increased, although the increase in sFasL was not significant. We suspect an effect of non-steroidal anti-inflammatory therapy on B cells, explaining the decrease of the percentage Fas+ B cells found within our samples. In healthy individuals, there was a noticeable pattern in the expression of FasL which mutually correlated to populations of mononuclear cells; this correlation was absent in the patients with Sjögren's syndrome.

Conclusions: Mononuclear cells expressing IL-2Rα+ had upregulated Fas in Sjögren's syndrome. However, the rate of apoptosis based on Annexin V staining and the Bcl-2/Bax expression was not observed in mononuclear cells. We suspect a functional role of abnormal levels of Fas and FasL which has not been cleared yet.

Keywords: Autoimmune disorders; B cells; CD95; CD95L; Fas; Fas Ligand; Monocytes; NSAIDs; Sjögren’s syndrome; T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Annexin A5
  • Apoptosis
  • Autoimmune Diseases*
  • Humans
  • Interleukin-2 Receptor alpha Subunit / metabolism
  • Sjogren's Syndrome*
  • bcl-2-Associated X Protein / metabolism
  • fas Receptor / metabolism

Substances

  • Annexin A5
  • Interleukin-2 Receptor alpha Subunit
  • bcl-2-Associated X Protein
  • fas Receptor