NK cells dysfunction in systemic lupus erythematosus: relation to disease activity

Ana Henriques, Luís Teixeira, Luís Inês, Tiago Carvalheiro, Ana Gonçalves, António Martinho, Maria Luísa Pais, José António Pereira da Silva, Artur Paiva

Research output: Contribution to journalArticlepeer-review

Abstract

Through their cytotoxic capacities and cytokine production, natural killer (NK) cells modulate autoimmune diseases. However, their role in the pathogenesis of systemic lupus erythematosus (SLE) has not been extensively studied. The aim of this study was to analyse the immunophenotypic and functional characteristics of the two major NK cell subsets in SLE and relate them with disease activity. Peripheral blood samples from 44 patients with active (n = 18) and inactive SLE (n = 26) and 30 controls were analysed by flow cytometry to evaluate NK cell subsets, according to: the differential expression of CXCR3 and CD57; expression of granzyme B and perforin; and production of interferon gamma (IFN-γ) and tumor necrosis alpha (TNF-α), after PMA/ionomycin activation. A clear decrease in absolute and relative numbers of circulating NK cells was found in SLE, particularly in active disease, while the proportions of the major NK cell subsets were unaffected. Active SLE was associated with a reduced CXCR3 expression on both NK cell subsets and a lower frequency of CD56(dim) NK cells expressing CXCR3. Furthermore, granzyme B expression was decreased in both SLE groups, but the percentage of NK cells expressing granzyme B and perforin was higher, particularly in active disease. We found a significant decrease in the percentage of CD56(bright) and CD56(dim) NK cells producing TNF-α and of its expression on CD56(dim) NK cells in active disease, while IFN-γ expression on CD56(bright) NK cells was increased in both SLE groups. Our findings suggest that NK cell subsets exhibit unique phenotypic and functional changes that are particularly evident in active SLE, and they may have the potential to affect the disease outcome.

Original languageEnglish
Pages (from-to)805-13
Number of pages9
JournalClinical rheumatology
Volume32
Issue number6
DOIs
Publication statusPublished - Jun 2013
Externally publishedYes

Keywords

  • Adult
  • CD56 Antigen/metabolism
  • CD57 Antigens/metabolism
  • Case-Control Studies
  • Cytokines/metabolism
  • Female
  • Flow Cytometry
  • Granzymes/metabolism
  • Humans
  • Interferon-gamma/metabolism
  • Ionomycin/chemistry
  • Killer Cells, Natural/metabolism
  • Lupus Erythematosus, Systemic/blood
  • Male
  • Middle Aged
  • Perforin/metabolism
  • Receptors, CXCR3/metabolism
  • Tumor Necrosis Factor-alpha/metabolism
  • Young Adult

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