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Peripheral blood natural killer cell percentages in granulomatosis with polyangiitis correlate with disease inactivity and stage

Merkt, Wolfgang ; Sturm, Prisca ; Lasitschka, Felix ; Tretter, Theresa ; Watzl, Carsten ; Saure, Daniel ; Hundemer, Michael ; Schwenger, Vedat ; Blank, Norbert ; Lorenz, Hanns-Martin ; Cerwenka, Adelheid

In: Arthritis Research & Therapy, 17 (2015), Nr. 337. pp. 1-11. ISSN 1465-9913

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Download (2MB) | Lizenz: Creative Commons LizenzvertragPeripheral blood natural killer cell percentages in granulomatosis with polyangiitis correlate with disease inactivity and stage by Merkt, Wolfgang ; Sturm, Prisca ; Lasitschka, Felix ; Tretter, Theresa ; Watzl, Carsten ; Saure, Daniel ; Hundemer, Michael ; Schwenger, Vedat ; Blank, Norbert ; Lorenz, Hanns-Martin ; Cerwenka, Adelheid underlies the terms of Creative Commons Attribution 3.0 Germany

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Abstract

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 CD56dim and CD56bright 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.

Item Type: Article
Journal or Publication Title: Arthritis Research & Therapy
Volume: 17
Number: 337
Publisher: BioMed Central
Place of Publication: London
Date Deposited: 08 Feb 2016 13:14
Date: 2015
ISSN: 1465-9913
Page Range: pp. 1-11
Faculties / Institutes: Service facilities > German Cancer Research Center (DKFZ)
Service facilities > Nierenzentrum Heidelberg
Medizinische Fakultät Heidelberg > Medizinische Universitäts-Klinik und Poliklinik
Medizinische Fakultät Heidelberg > Institut für Medizinische Biometrie und Informatik
Medizinische Fakultät Heidelberg > Pathologisches Institut
Subjects: 610 Medical sciences Medicine
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