A myelopoiesis gene signature during remission in anti-neutrophil cytoplasm antibody-associated vasculitis does not predict relapses but seems to reflect ongoing prednisolone therapy.

作者: T. Kurz , M. Weiner , C. Skoglund , S. Basnet , P. Eriksson

DOI: 10.1111/CEI.12236

关键词: BiologyImmunologyPrednisoloneMyeloperoxidaseProteinase 3OncogeneEnhancer bindingPeripheral blood mononuclear cellMyelopoiesisGene signature

摘要: A myelopoiesis gene signature in circulating leucocytes, exemplified by increased myeloperoxidase (MPO) and proteinase 3 (PR3) mRNA levels, has been reported patients with active anti-neutrophil cytoplasm antibody-associated vasculitis (AAV), to a lesser extent during remission. We hypothesized that this could predict disease relapse. levels of PR3, MPO, selected transcription factors [CCAAT/enhancer binding protein α (CEBP-α), CCAAT/enhancer β (CEBP-β), SPI1/PU.1-related factor (SPIB), spleen focus forming virus proviral integration oncogene, PU.1 homologue (SPI1)] microRNAs (miRNAs) from patient control peripheral blood mononuclear cells (PBMC) polymorphonuclear (PMN) were analysed associated clinical data. Patients stable remission had higher for PR3 (PBMC, PMN) MPO (PBMC). SPIB correlated positively controls but negatively PBMC. Statistically significant correlations existed between several miRNAs controls, not patients. PR3/MPO previous or future relapses, steroid treatment. Prednisolone doses linked miR-155-5p, miR-339-5p miR-221, miR-361 miR-505 (PMN). PBMC time since last flare, leucocyte count estimated glomerular filtration rate. Our results show elevated AAV do The origin seems multi-factorial, an important explainable prednisolone action. Gene signatures undergoing treatment should therefore be interpreted accordingly.

参考文章(100)
Trevor E. Davis, Katalin Kis-Toth, Attila Szanto, George C. Tsokos, Glucocorticoids suppress T cell function by up-regulating microRNA-98. Arthritis & Rheumatism. ,vol. 65, pp. 1882- 1890 ,(2013) , 10.1002/ART.37966
Michael F. Denny, Srilakshmi Yalavarthi, Wenpu Zhao, Seth G. Thacker, Marc Anderson, Ashley R. Sandy, W. Joseph McCune, Mariana J. Kaplan, A Distinct Subset of Proinflammatory Neutrophils Isolated from Patients with Systemic Lupus Erythematosus Induces Vascular Damage and Synthesizes Type I IFNs The Journal of Immunology. ,vol. 184, pp. 3284- 3297 ,(2010) , 10.4049/JIMMUNOL.0902199
Antonio Curti, Elisa Ferri, Simona Pandolfi, Alessandro Isidori, Roberto M. Lemoli, Dendritic Cell Differentiation The Journal of Immunology. ,vol. 172, pp. 3- 4 ,(2004) , 10.4049/JIMMUNOL.172.1.3
U. Specks, E. L. Matteson, CD Pusey, Cgm Kallenburg, P. Bacon, RA Luqmani, N Basu, Richard Watts, J Stone, G. Hoffman, Dgi Scott, K Takahashi, L. Guillevin, F Ferrario, N Rasmussen, MC Cid, A Rees, P Lamprecht, E. C. Hagen, J. C. Jennette, Jayne, LF Flores-Suarez, CA Langford, R. J. Falk, W. L. Gross, S Ozen, A. D. Mahr, P. A. Merkel, Revised international Chapel Hill consensus conference nomenclature of vasculitides ,(2013)
M. Abdgawad, L. Gunnarsson, A. A. Bengtsson, P. Geborek, L. Nilsson, M. Segelmark, T. Hellmark, Elevated neutrophil membrane expression of proteinase 3 is dependent upon CD177 expression Clinical and Experimental Immunology. ,vol. 161, pp. 89- 97 ,(2010) , 10.1111/J.1365-2249.2010.04154.X
S. M. Ohlsson, Å. Pettersson, S. Ohlsson, D. Selga, A. A. Bengtsson, M. Segelmark, T. Hellmark, Phagocytosis of apoptotic cells by macrophages in anti-neutrophil cytoplasmic antibody-associated systemic vasculitis. Clinical and Experimental Immunology. ,vol. 170, pp. 47- 56 ,(2012) , 10.1111/J.1365-2249.2012.04633.X
Y. Shoenfeld, Y. Gurewich, L.A. Gallant, J. Pinkhas, Prednisone-induced leukocytosis The American Journal of Medicine. ,vol. 71, pp. 773- 778 ,(1981) , 10.1016/0002-9343(81)90363-6
Elena Vigorito, Kerry L. Perks, Cei Abreu-Goodger, Sam Bunting, Zou Xiang, Susan Kohlhaas, Partha P. Das, Eric A. Miska, Antony Rodriguez, Allan Bradley, Kenneth G.C. Smith, Cristina Rada, Anton J. Enright, Kai-Michael Toellner, Ian C.M. MacLennan, Martin Turner, microRNA-155 Regulates the Generation of Immunoglobulin Class-Switched Plasma Cells Immunity. ,vol. 27, pp. 847- 859 ,(2007) , 10.1016/J.IMMUNI.2007.10.009
Dominic J. Ciavatta, JiaJin Yang, Gloria A. Preston, Anshul K. Badhwar, Hong Xiao, Peter Hewins, Carla M. Nester, William F. Pendergraft, Terry R. Magnuson, J. Charles Jennette, Ronald J. Falk, Epigenetic basis for aberrant upregulation of autoantigen genes in humans with ANCA vasculitis Journal of Clinical Investigation. ,vol. 120, pp. 3209- 3219 ,(2010) , 10.1172/JCI40034
Y. Dai, Y.-S. Huang, M. Tang, T.-Y. Lv, C.-X. Hu, Y.-H. Tan, Z.-M. Xu, Y.-B. Yin, Microarray analysis of microRNA expression in peripheral blood cells of systemic lupus erythematosus patients. Lupus. ,vol. 16, pp. 939- 946 ,(2007) , 10.1177/0961203307084158