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Clin Rheumatol (2013) 32:805813
DOI 10.1007/s10067-013-2176-8
ORIGINAL ARTICLE
NK cells dysfunction in systemic lupus erythematosus: relation to disease activity
Ana Henriques & Lus Teixeira & Lus Ins &
Tiago Carvalheiro & Ana Gonalves & Antnio Martinho &
Maria Lusa Pais & Jos Antnio Pereira da Silva &
Artur Paiva
Received: 4 May 2012 /Revised: 14 December 2012 /Accepted: 14 January 2013 /Published online: 2 February 2013 # Clinical Rheumatology 2013
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-) and tumor necrosis alpha (TNF-), 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 CD56dim 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 CD56bright and CD56dim NK cells
producing TNF- and of its expression on CD56dim NK cells
in active disease, while IFN- expression on CD56bright 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.
Keywords CXCR3 . Cytokines . Granzyme B . NK cell subsets . Systemic lupus erythematosus
Introduction
Systemic lupus erythematosus (SLE) is a multifactorial auto-immune disease characterized by a wide array of clinical manifestations, from skin and mucosal lesions...