STAT-5 is activated constitutively in T cells, B cells and monocytes from patients with primary Sjögren's syndrome

Clin Exp Immunol. 2015 Jul;181(1):29-38. doi: 10.1111/cei.12614. Epub 2015 Apr 23.

Abstract

The expression and phosphorylation of signal transducer and activator of transcription-1 (STAT-1) have been shown to be markedly increased in the salivary gland epithelial cells of patients with primary Sjögren's syndrome (pSS). The present aim was to investigate the activation status of different STAT proteins in peripheral blood (PB) lymphocytes and monocytes, and their correlations with clinical parameters in patients with pSS. To this end, PB samples were drawn from 16 patients with active pSS and 16 healthy blood donors, and the phosphorylation of STAT-1, -3, -4, -5 and -6 proteins was studied in T cells, B cells and monocytes using multi-colour flow cytometry. In addition, mRNA expression of STAT molecules in PB mononuclear cells (PBMC) was studied with quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). Basal phosphorylation of STAT-5 was found to be significantly higher in PB T cells, B cells and monocytes in patients with pSS than in healthy controls. The expression of STAT-5 mRNA was not increased in PBMC. pSTAT-5 levels in B cells and monocytes showed a significant correlation with serum immunoglobulin (Ig)G levels and anti-SSB antibody titres. Constitutive STAT-5 activation in monocytes and CD4(+) T cells was associated with purpura. There were no major differences in the activation of other STATs between pSS patients and healthy controls. In conclusion, STAT-5 is activated constitutively in PB leucocytes in patients with pSS, and basal STAT-5 phosphorylation seems to associate with hypergammaglobulinaemia, anti-SSB antibody production and purpura.

Keywords: ESSDAI; ESSPRI; PBMC; STAT; Sjögren's syndrome; phosphorylation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Autoantigens / immunology*
  • B-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / immunology*
  • Enzyme Activation
  • Female
  • Humans
  • Immunoglobulin G / blood*
  • Leukocytes, Mononuclear / immunology
  • Male
  • Middle Aged
  • Phosphorylation
  • RNA, Messenger / biosynthesis
  • Ribonucleoproteins / immunology*
  • SS-B Antigen
  • STAT1 Transcription Factor / genetics
  • STAT1 Transcription Factor / metabolism
  • STAT3 Transcription Factor / genetics
  • STAT3 Transcription Factor / metabolism
  • STAT4 Transcription Factor / genetics
  • STAT4 Transcription Factor / metabolism
  • STAT5 Transcription Factor / genetics
  • STAT5 Transcription Factor / metabolism*
  • STAT6 Transcription Factor / genetics
  • STAT6 Transcription Factor / metabolism
  • Sjogren's Syndrome / immunology*

Substances

  • Autoantigens
  • Immunoglobulin G
  • RNA, Messenger
  • Ribonucleoproteins
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • STAT4 Transcription Factor
  • STAT4 protein, human
  • STAT5 Transcription Factor
  • STAT6 Transcription Factor
  • STAT6 protein, human