Multiple sclerosis treatment effects on plasma cytokine receptor levels

被引：6

作者：

Bedri, Sahl Khalid

Fink, Katharina

Manouchehrinia, Ali

Lundstrom, Wangko

Kockum, Ingrid

Olsson, Tomas

Hillert, Jan

Glaser, Anna ^{[1
]}

机构：

[1] Karolinska Inst, Dept Clin Neurosci, Widerstromska Huset Tomtebodavagen 18A,Floor 5, S-17177 Stockholm, Sweden

来源：

CLINICAL IMMUNOLOGY | 2018年 / 187卷

基金：

瑞典研究理事会;

关键词：

Multiple sclerosis; Biomarkers; Natalizumab; Fingolimod; Soluble cytokine receptor; pharmacogenomics; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; PLACEBO-CONTROLLED TRIAL; T-CELLS; HISTONE DEACETYLASE; TRICHOSTATIN-A; INTERLEUKIN-7; RECEPTOR; NATALIZUMAB TREATMENT; SOLUBLE IL-6R; FINGOLIMOD; INHIBITOR;

D O I：

10.1016/j.clim.2017.08.023

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Genetic variants within some cytokine receptor genes have been associated with MS susceptibility, including IL7RA and IL2RA. As these genes are expressed by cells targeted by immune-modulatory drugs, we explored the potential role of their gene products as biomarkers in monitoring MS treatment. We assessed the impact of natalizumab followed by fingolimod on the intra-individual changes of plasma protein levels of sIL-7R alpha, sIL-2R alpha and also sIL-6R and sgp130 in MS patients. During natalizumab treatment we observed a decline in sgp130 and sIL-7R alpha levels, while subsequent fingolimod treatment lead to increased sgp130 and sIL-7R alpha and decreased sIL-2R alpha levels. In addition, during fingolimod treatment sIL-7R alpha levels were increasing significantly more in patients homozygous for the MS risk genotype of rs6897932. We also observed an effect of the MS associated rs71624119 on sgp130 levels. These results may elucidate the pharmacodynamics of treatments and help identify biomarkers for MS outcomes. (C) 2017 Elsevier Inc. All rights reserved.

引用

页码：15 / 25

页数：11

共 60 条

[1] Interleukins 1β and 6 but not transforming growth factor-β are essential for the differentiation of interleukin 17-producing human T helper cells [J].

Acosta-Rodriguez, Eva V. ;

Napolitani, Giorgio ;

Lanzavecchia, Antonio ;

Sallusto, Federica .

NATURE IMMUNOLOGY, 2007, 8 (09) :942-949

[2] Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis [J].

Beecham, Ashley H. ;

Patsopoulos, Nikolaos A. ;

Xifara, Dionysia K. ;

Davis, Mary F. ;

Kemppinen, Anu ;

Cotsapas, Chris ;

Shah, Tejas S. ;

Spencer, Chris ;

Booth, David ;

Goris, An ;

Oturai, Annette ;

Saarela, Janna ;

Fontaine, Bertrand ;

Hemmer, Bernhard ;

Martin, Claes ;

Zipp, Frauke ;

D'Alfonso, Sandra ;

Martinelli-Boneschi, Filippo ;

Taylor, Bruce ;

Harbo, Hanne F. ;

Kockum, Ingrid ;

Hillert, Jan ;

Olsson, Tomas ;

Ban, Maria ;

Oksenberg, Jorge R. ;

Hintzen, Rogier ;

Barcellos, Lisa F. ;

Agliardi, Cristina ;

Alfredsson, Lars ;

Alizadeh, Mehdi ;

Anderson, Carl ;

Andrews, Robert ;

Sondergaard, Helle Bach ;

Baker, Amie ;

Band, Gavin ;

Baranzini, Sergio E. ;

Barizzone, Nadia ;

Barrett, Jeffrey ;

Bellenguez, Celine ;

Bergamaschi, Laura ;

Bernardinelli, Luisa ;

Berthele, Achim ;

Biberacher, Viola ;

Binder, Thomas M. C. ;

Blackburn, Hannah ;

Bomfim, Izaura L. ;

Brambilla, Paola ;

Broadley, Simon ;

Brochet, Bruno ;

Brundin, Lou .

NATURE GENETICS, 2013, 45 (11) :1353-+

[3] Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells [J].

Bettelli, E ;

Carrier, YJ ;

Gao, WD ;

Korn, T ;

Strom, TB ;

Oukka, M ;

Weiner, HL ;

Kuchroo, VK .

NATURE, 2006, 441 (7090) :235-238

[4] Pharmacodynamic Effects of Steady-State Fingolimod on Antibody Response in Healthy Volunteers: A 4-Week, Randomized, Placebo-Controlled, Parallel-Group, Multiple-Dose Study [J].

Boulton, Craig ;

Meiser, Karin ;

David, Olivier J. ;

Schmouder, Robert .

JOURNAL OF CLINICAL PHARMACOLOGY, 2012, 52 (12) :1879-1890

[5] The immune modulator FTY720 targets sphingosine 1-phosphate receptors [J].

Brinkmann, V ;

Davis, MD ;

Heise, CE ;

Albert, R ;

Cottens, S ;

Hof, R ;

Bruns, C ;

Prieschl, E ;

Baumruker, T ;

Hiestand, P ;

Foster, CA ;

Zollinger, M ;

Lynch, KR .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (24) :21453-21457

[6] Phenotypical and functional characterization of T helper 17 cells in multiple sclerosis [J].

Brucklacher-Waldert, Verena ;

Sturner, Klarissa ;

Kolster, Manuela ;

Wolthausen, Julia ;

Tolosa, Eva .

BRAIN, 2009, 132 :3329-3341

[7] Influence of Membrane CD25 Stability on T Lymphocyte Activity: Implications for Immunoregulation [J].

Brusko, Todd M. ;

Wasserfall, Clive H. ;

Hulme, Maigan A. ;

Cabrera, Roniel ;

Schatz, Desmond ;

Atkinson, Mark A. .

PLOS ONE, 2009, 4 (11)

[8] Transcriptional therapy with the histone deacetylase inhibitor trichostatin A ameliorates experimental autoimmune encephalomyelitis [J].

Camelo, S ;

Iglesias, AH ;

Hwang, D ;

Due, B ;

Ryu, H ;

Smith, K ;

Gray, SG ;

Imitola, J ;

Duran, G ;

Assaf, B ;

Langley, B ;

Khoury, SJ ;

Stephanopoulos, G ;

De Girolami, U ;

Ratan, RR ;

Ferrante, RJ ;

Dangond, F .

JOURNAL OF NEUROIMMUNOLOGY, 2005, 164 (1-2) :10-21

[9] Genetic Drivers of Epigenetic and Transcriptional Variation in Human Immune Cells [J].

Chen, Lu ;

Ge, Bing ;

Casale, Francesco Paolo ;

Vasquez, Louella ;

Kwan, Tony ;

Garrido-Martin, Diego ;

Watt, Stephen ;

Yan, Ying ;

Kundu, Kousik ;

Ecker, Simone ;

Datta, Avik ;

Richardson, David ;

Burden, Frances ;

Mead, Daniel ;

Mann, Alice L. ;

Maria Fernandez, Jose ;

Rowlston, Sophia ;

Wilder, Steven P. ;

Farrow, Samantha ;

Shao, Xiaojian ;

Lambourne, John J. ;

Redensek, Adriana ;

Albers, Cornelis A. ;

Amstislavskiy, Vyacheslav ;

Ashford, Sofie ;

Berentsen, Kim ;

Bomba, Lorenzo ;

Bourque, Guillaume ;

Bujold, David ;

Busche, Stephan ;

Caron, Maxime ;

Chen, Shu-Huang ;

Cheung, Warren ;

Delaneau, Oliver ;

Dermitzakis, Emmanouil T. ;

Elding, Heather ;

Colgiu, Irina ;

Bagger, Frederik O. ;

Flicek, Paul ;

Habibi, Ehsan ;

Iotchkova, Valentina ;

Janssen-Megens, Eva ;

Kim, Bowon ;

Lehrach, Hans ;

Lowy, Ernesto ;

Mandoli, Amit ;

Matarese, Filomena ;

Maurano, Matthew T. ;

Morris, John A. ;

Pancaldi, Vera .

CELL, 2016, 167 (05) :1398-+

[10] Limited statistical evidence for shared genetic effects of eQTLs and autoimmune-disease-associated loci in three major immune-cell types [J].

Chun, Sung ;

Casparino, Alexandra ;

Patsopoulos, Nikolaos A. ;

Croteau-Chonka, Damien C. ;

Raby, Benjamin A. ;

De Jager, Philip L. ;

Sunyaev, Shamil R. ;

Cotsapas, Chris .

NATURE GENETICS, 2017, 49 (04) :600-+

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