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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Arthritis+Res+Ther
2015 ; 17
(ä): 337
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gab.com Text
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Peripheral blood natural killer cell percentages in granulomatosis with
polyangiitis correlate with disease inactivity and stage
#MMPMID26589807
Merkt W
; Sturm P
; Lasitschka F
; Tretter T
; Watzl C
; Saure D
; Hundemer M
; Schwenger V
; Blank N
; Lorenz HM
; Cerwenka A
Arthritis Res Ther
2015[Nov]; 17
(ä): 337
PMID26589807
show ga
INTRODUCTION: The role of CD3-CD56+ natural killer (NK) cells in granulomatosis
with polyangiitis (GPA) is poorly understood. Recently, it has been shown that
peripheral blood NK cells can kill renal microvascular endothelial cells,
suggesting a pathogenic role of NK cells in this disease. So far, subset
distribution, phenotype, and function of peripheral blood NK cells in relation to
GPA disease activity have not been elucidated. Moreover, it is not known whether
NK cells infiltrate GPA tissue lesions. METHODS: Paraffin sections of GPA
granulomas and controls were stained with anti-CD56 and anti-CD3 antibodies.
Peripheral blood lymphocyte subsets were analyzed by flow cytometry. NK cell
degranulation was analyzed using cocultures of patient PBMCs with target cells
and surface expression of CD107a. Clinical data were extracted from medical
records. Statistical analysis was performed in an exploratory way. RESULTS: CD56+
cells were not detectable in active granulomatous GPA lesions but were found
frequently in granulomas from tuberculosis and sarcoidosis patients. In GPA, the
proportion of NK cells among peripheral blood lymphocytes correlated negatively
with the Birmingham Vasculitis Activity Score (BVAS) (n?=?28). Accordingly, NK
cell percentages correlated positively with the duration of remission (n?=?28)
and were significantly higher in inactive GPA (BVAS?=?0, n?=?17) than in active
GPA, healthy controls (n?=?29), and inactive control diseases (n?=?12). The
highest NK cell percentages were found in patients with long-term remission and
tapered immunosuppressive therapy. NK cell percentages >18.5% of peripheral blood
lymphocytes (n?=?12/28) determined GPA inactivity with a specificity of 100%. The
differentiation into CD56(dim) and CD56(bright) NK cell subsets was unchanged in
GPA (n?=?28), irrespective of disease activity. Similar surface expression of the
activating NK cell-receptors (NKp30, NKp46, and NKG2D) was determined. Like in
healthy controls, GPA NK cells degranulated in the presence of NK cell receptor
ligand bearing epithelial and lymphatic target cells. CONCLUSIONS: NK cells were
not detectable in GPA granulomas. Peripheral blood NK cell percentages positively
correlate with the suppression of GPA activity and could serve as a biomarker for
GPA activity. Peripheral blood NK cells in GPA patients are mature NK cells with
preserved immune recognition.
|Adult
[MESH]
|Aged
[MESH]
|Aged, 80 and over
[MESH]
|Cells, Cultured
[MESH]
|Disease Progression
[MESH]
|Female
[MESH]
|Granulomatosis with Polyangiitis/*metabolism/*pathology
[MESH]