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Transcriptome analysis shows activation of circulating CD8+ T-cells in severe asthma
Eleni Tsitsiou PhD 1*, Andrew Euan Williams PhD 2*, Sterghios A. Moschos PhD 3, Ketan Patel PhD 3, Christos Rossios PhD 2, Xiaoying Jiang PhD 1, Oona-Delpuech Adams PhD 3, Patricia Macedo MD 2, Richard Booton PhD 1, David Gideon MD 2, Kian Fan Chung PhD 2 and Mark A. Lindsay PhD 1,2,4
1 Respiratory Research Group, Faculty of Medical and Human Sciences, UniversityofManchester; NIHR Translational Research Facility in Respiratory Medicine, University Hospital of South Manchester, United Kingdom
2 Airways Disease, National Heart and Lung Institute, Imperial College, London & Royal Brompton NIHR Biomedical Research Unit, United Kingdom
3 Pfizer Global Research and Development, Sandwich, Kent, United Kingdom
4 Department of Pharmacy and Pharmacology, University of Bath, Claverton Down, Bath, United Kingdom
* These authors contributed equally to this publication
Correspondence and requests for reprints should be addressed to Mark A. Lindsay, Ph.D. Department of Pharmacy and Pharmacology, University of Bath, Claverton Down, Bath, BA2 7AY United Kingdom Fax: +44 1225 1225 386114,: Tel: +44 1225 386783; E.mail:
Supplemental Table E1 Up-regulated mRNAs in CD4+ T-cells in severe asthmatics. Circulating CD4+ T-cells were isolated from 8 non-asthmatics control and 8 severe asthmatics and the profile of mRNAs expression was determine using U133 Affymetric microarrays. This table lists those mRNAs whose expression was increased in the CD4+ obtained from severe asthmatics compared with non-asthmatics controls and is expressed as fold change. The mechanism of statistical analysis is described in the methods section.
Probeset / P Value / FDR / Fold change / Direction / Symbol / Name204446_s_at / 0.0000 / 0.0205 / 2.24 / UP / ALOX5 / Arachidonate 5-lipoxygenase
201302_at / 0.0002 / 0.0413 / 1.90 / UP / ANXA4 / annexin A4
222761_at / 0.0001 / 0.0260 / 1.55 / UP / BIVM / basic, immunoglobulin-like variable motif containing
205557_at / 0.0001 / 0.0248 / 2.57 / UP / BPI / bactericidal/permeability-increasing protein
238545_at / 0.0001 / 0.0255 / 1.55 / UP / BRD7 / bromodomain containing 7
210244_at / 0.0004 / 0.0458 / 3.30 / UP / CAMP / cathelicidin antimicrobial peptide
227156_at / 0.0002 / 0.0349 / 1.71 / UP / CASK / Peripheral plasma membrane protein CASK
200663_at / 0.0005 / 0.0492 / 1.70 / UP / CD63 / CD63 molecule
211657_at / 0.0000 / 0.0213 / 2.41 / UP / CEACAM6 / carcinoembryonic antigen-related cell adhesion molecule 6 (non-specific cross reacting antigen)
206676_at / 0.0000 / 0.0100 / 5.65 / UP / CEACAM8 / carcinoembryonic antigen-related cell adhesion molecule 8
211862_x_at / 0.0004 / 0.0459 / 1.60 / UP / CFLAR / FLAME-1
207269_at / 0.0002 / 0.0397 / 4.29 / UP / DEFA4 / defensin, alpha 4, corticostatin
203765_at / 0.0004 / 0.0470 / 2.57 / UP / GCA / grancalcin, EF-hand calcium binding protein
212531_at / 0.0000 / 0.0232 / 4.74 / UP / LCN2 / lipocalin 2
215123_at / 0.0002 / 0.0398 / 2.38 / UP / LOC23117 / KIAA0220-like protein
205033_s_at / 0.0000 / 0.0209 / 6.16 / UP / LOC728358 / defensin, alpha 1
202018_s_at / 0.0000 / 0.0219 / 5.05 / UP / LTF / lactotransferrin
227379_at / 0.0002 / 0.0377 / 1.52 / UP / MBOAT1 / membrane bound O-acyltransferase domain containing 1
231688_at / 0.0001 / 0.0247 / 3.61 / UP / MMP8 / MMP-8 (collagenase 2)
204959_at / 0.0003 / 0.0442 / 2.74 / UP / MNDA / myeloid cell nuclear differentiation antigen
228962_at / 0.0001 / 0.0257 / 1.55 / UP / PDE4D / PDE4D (cAMP-specific phosphodiesterase 4D/ HSPDE4D)
1552622_s_at / 0.0002 / 0.0398 / 1.88 / UP / POLR2J2 / DNA directed RNA polymerase II polypeptide J-related
233813_at / 0.0000 / 0.0233 / 1.60 / UP / PPP1R16B / protein phosphatase 1, regulatory (inhibitor) subunit 16B
207957_s_at / 0.0006 / 0.0497 / 1.80 / UP / PRKCB1 / Protein kinase C beta-I type(PKC-beta-1)
220570_at / 0.0006 / 0.0495 / 1.69 / UP / RETN / resistin
206851_at / 0.0002 / 0.0364 / 1.97 / UP / RNASE3 / ribonuclease, RNase A family, 3 (eosinophil cationic protein)
232231_at / 0.0005 / 0.0481 / 2.01 / UP / RUNX2 / runt-related transcription factor 2
205863_at / 0.0000 / 0.0231 / 4.71 / UP / S100A12 / S100 calcium binding protein A12
202917_s_at / 0.0001 / 0.0249 / 4.81 / UP / S100A8 / S100 calcium binding protein A8
203535_at / 0.0001 / 0.0254 / 5.02 / UP / S100A9 / S100 calcium binding protein A9
204351_at / 0.0001 / 0.0238 / 3.35 / UP / S100P / S100 calcium binding protein P
220924_s_at / 0.0005 / 0.0485 / 1.62 / UP / SLC38A2 / Amino acid transporter system A2 (ATA2)
1556601_a_at / 0.0006 / 0.0499 / 1.67 / UP / SPATA13 / spermatogenesis associated 13
201859_at / 0.0004 / 0.0458 / 1.88 / UP / SRGN / serglycin
201858_s_at / 0.0004 / 0.0465 / 1.97 / UP / SRGN / serglycin
201061_s_at / 0.0000 / 0.0100 / 2.35 / UP / STOM / stomatin
243423_at / 0.0003 / 0.0423 / 1.63 / UP / TNIP1 / TNFAIP3 interacting protein 1
223741_s_at / 0.0003 / 0.0420 / 1.83 / UP / TTYH2 / tweety homolog 2 (Drosophila)
224967_at / 0.0001 / 0.0342 / 2.04 / UP / UGCG / UDP-glucose ceramide glucosyltransferase(UGCG)
206111_at / 0.0000 / 0.0100 / 2.52 / UP / ZNF749 / zinc finger protein 749
Supplemental Table E2 Up-regulated mRNAs in CD8+ T-cells in severe asthmatics. Circulating CD8+ T-cells were isolated from 8 non-asthmatics control and 8 severe asthmatics and the profile of mRNAs expression was determine using U133 Affymetric microarrays. This table lists those mRNAs whose expression was increased in the CD8+ obtained from severe asthmatics compared with non-asthmatics controls and is expressed as fold change. The mechanism of statistical analysis is described in the methods section.
Probeset / P Value / FDR / Fold change / Direction / Symbol / Name235435_at / 0.0018 / 0.0051 / 1.53 / UP / AASDH / aminoadipate-semialdehyde dehydrogenase
202805_s_at / 0.0252 / 0.0247 / 1.59 / UP / ABCC1 / Multidrug resistance-associated protein 1(MRP1) (ABCC1)
204567_s_at / 0.0000 / 0.0000 / 1.85 / UP / ABCG1 / White homolog (ABCG1)
235432_at / 0.0033 / 0.0073 / 1.88 / UP / ACAD11 / acyl-Coenzyme A dehydrogenase family, member 11
221669_s_at / 0.0024 / 0.0061 / 1.90 / UP / ACAD8 / acyl-Coenzyme A dehydrogenase family, member 8
238825_at / 0.0050 / 0.0093 / 1.53 / UP / ACRC / acidic repeat containing
201662_s_at / 0.0228 / 0.0231 / 1.53 / UP / ACSL3 / acyl-CoA synthetase long-chain family member 3
229725_at / 0.0060 / 0.0104 / 1.81 / UP / ACSL6 / acyl-CoA synthetase long-chain family member 6
202666_s_at / 0.0045 / 0.0087 / 1.59 / UP / ACTL6A / actin-like 6A
1558015_s_at / 0.0262 / 0.0253 / 1.58 / UP / ACTR2 / ARP2 actin-related protein 2 homolog (yeast)
200728_at / 0.0691 / 0.0466 / 2.01 / UP / ACTR2 / ARP2 actin-related protein 2 homolog (yeast)
203935_at / 0.0004 / 0.0020 / 1.72 / UP / ACVR1 / Activin receptor type I (ACTR-I / ALK-2)
1552519_at / 0.0005 / 0.0023 / 1.55 / UP / ACVR1C / Activin receptor-like kinase 7 (ALK-7)(geneseqp)
203865_s_at / 0.0008 / 0.0031 / 1.52 / UP / ADARB1 / adenosine deaminase, RNA-specific, B1 (RED1 homolog rat)
219384_s_at / 0.0126 / 0.0161 / 1.61 / UP / ADAT1 / adenosine deaminase, tRNA-specific 1
221893_s_at / 0.0021 / 0.0056 / 1.53 / UP / ADCK2 / aarF domain containing kinase 2
205882_x_at / 0.0225 / 0.0230 / 1.64 / UP / ADD3 / adducin 3 (gamma)
201752_s_at / 0.0451 / 0.0354 / 1.55 / UP / ADD3 / adducin 3 (gamma)
208848_at / 0.0499 / 0.0378 / 1.61 / UP / ADH5 / alcohol dehydrogenase 5 (class III), chi polypeptide
204119_s_at / 0.0522 / 0.0389 / 1.53 / UP / ADK / Adenosine kinase
224455_s_at / 0.0701 / 0.0470 / 1.64 / UP / ADPGK / ADP-dependent glucokinase
204333_s_at / 0.0027 / 0.0064 / 1.98 / UP / AGA / Aspartylglucosaminidase
225114_at / 0.0000 / 0.0002 / 2.18 / UP / AGPS / alkylglycerone phosphate synthase
226783_at / 0.0002 / 0.0012 / 1.56 / UP / AGXT2L2 / Aminotransferase homologue MGC:15875
214766_s_at / 0.0004 / 0.0021 / 1.52 / UP / AHCTF1 / AT hook containing transcription factor 1
200848_at / 0.0252 / 0.0247 / 1.72 / UP / AHCYL1 / S-adenosylhomocysteine hydrolase-like 1
220199_s_at / 0.0351 / 0.0303 / 2.24 / UP / AIDA / axin interactor, dorsalization associated
224151_s_at / 0.0127 / 0.0161 / 1.52 / UP / AK3 / Adenylate kinase 3 (AK3)
210625_s_at / 0.0421 / 0.0339 / 1.55 / UP / AKAP1 / A kinase (PRKA) anchor protein 1
236006_s_at / 0.0000 / 0.0001 / 1.92 / UP / AKAP10 / A kinase (PRKA) anchor protein 10
218064_s_at / 0.0080 / 0.0123 / 1.64 / UP / AKAP8L / A kinase (PRKA) anchor protein 8-like
215483_at / 0.0002 / 0.0013 / 1.96 / UP / AKAP9 / A kinase (PRKA) anchor protein (yotiao) 9
217893_s_at / 0.0039 / 0.0080 / 2.56 / UP / AKIRIN1 / akirin 1
223894_s_at / 0.0590 / 0.0421 / 1.78 / UP / AKTIP / AKT interacting protein
203608_at / 0.0302 / 0.0277 / 1.64 / UP / ALDH5A1 / NAD+-dependent succinic semialdehydedehydrogenase
221589_s_at / 0.0001 / 0.0011 / 1.51 / UP / ALDH6A1 / aldehyde dehydrogenase 6 family, member A1
1553101_a_at / 0.0237 / 0.0237 / 2.06 / UP / ALKBH5 / alkB, alkylation repair homolog 5 (E. coli)
1553220_at / 0.0021 / 0.0056 / 1.51 / UP / ALS2CR13 / amyotrophic lateral sclerosis 2 (juvenile) chromosome region, candidate 13
226421_at / 0.0002 / 0.0013 / 1.51 / UP / AMMECR1 / Alport syndrome, mental retardation, midface hypoplasia and elliptocytosis chromosomal region, gene
226258_at / 0.0002 / 0.0012 / 1.76 / UP / AMN1 / antagonist of mitotic exit network 1 homolog (S. cerevisiae)
208722_s_at / 0.0042 / 0.0084 / 2.08 / UP / ANAPC5 / anaphase promoting complex subunit 5
221826_at / 0.0009 / 0.0034 / 1.68 / UP / ANGEL2 / angel homolog 2 (Drosophila)
223093_at / 0.0090 / 0.0132 / 1.51 / UP / ANKH / ankylosis, progressive homolog (mouse)
229457_at / 0.0010 / 0.0035 / 1.54 / UP / ANKHD1 / ankyrin repeat and KH domain containing 1
212200_at / 0.0009 / 0.0034 / 1.74 / UP / ANKLE2 / ankyrin repeat and LEM domain containing 2
226663_at / 0.0091 / 0.0133 / 1.99 / UP / ANKRD10 / ankyrin repeat domain 10
218093_s_at / 0.0192 / 0.0207 / 1.80 / UP / ANKRD10 / ankyrin repeat domain 10
234701_at / 0.0001 / 0.0010 / 1.58 / UP / ANKRD11 / ankyrin repeat domain 11
219437_s_at / 0.0070 / 0.0113 / 1.60 / UP / ANKRD11 / ankyrin repeat domain 11
216563_at / 0.0000 / 0.0002 / 2.30 / UP / ANKRD12 / ankyrin repeat domain 12
212289_at / 0.0065 / 0.0109 / 1.65 / UP / ANKRD12 / ankyrin repeat domain 12
212286_at / 0.0084 / 0.0127 / 1.53 / UP / ANKRD12 / ankyrin repeat domain 12
223418_x_at / 0.0023 / 0.0059 / 1.63 / UP / ANKRD13C / ankyrin repeat domain 13C
212211_at / 0.0055 / 0.0099 / 2.06 / UP / ANKRD17 / ankyrin repeat domain 17
220940_at / 0.0003 / 0.0018 / 1.87 / UP / ANKRD36B / ankyrin repeat domain 36B
208103_s_at / 0.0168 / 0.0192 / 1.51 / UP / ANP32E / acidic (leucine-rich) nuclear phosphoprotein 32 family, member E
209369_at / 0.0012 / 0.0041 / 3.23 / UP / ANXA3 / annexin A3
1553165_at / 0.0032 / 0.0071 / 1.73 / UP / AP1GBP1 / AP1 gamma subunit binding protein 1
232387_at / 0.0200 / 0.0213 / 1.51 / UP / AP1GBP1 / AP1 gamma subunit binding protein 1
223025_s_at / 0.0015 / 0.0045 / 1.65 / UP / AP1M1 / adaptor-related protein complex 1, mu 1 subunit
223024_at / 0.0240 / 0.0240 / 1.52 / UP / AP1M1 / adaptor-related protein complex 1, mu 1 subunit
219994_at / 0.0178 / 0.0198 / 1.68 / UP / APBB1IP / amyloid beta (A4) precursor protein-binding, family B, member 1 interacting protein
213289_at / 0.0354 / 0.0304 / 1.59 / UP / APOOL / apolipoprotein O-like
202629_at / 0.0003 / 0.0016 / 1.63 / UP / APPBP2 / amyloid beta precursor protein (cytoplasmic tail) binding protein 2
222538_s_at / 0.0359 / 0.0307 / 2.02 / UP / APPL1 / adaptor protein, phosphotyrosine interaction, PH domain and leucine zipper containing 1
201176_s_at / 0.0330 / 0.0292 / 1.55 / UP / ARCN1 / archain 1
1565651_at / 0.0045 / 0.0087 / 1.63 / UP / ARF1 / ADP-ribosylation factor 1
202955_s_at / 0.0214 / 0.0222 / 1.80 / UP / ARFGEF1 / ADP-ribosylation factor guanine nucleotide-exchange factor 1(brefeldin A-inhibited)
216266_s_at / 0.0255 / 0.0249 / 2.25 / UP / ARFGEF1 / ADP-ribosylation factor guanine nucleotide-exchange factor 1(brefeldin A-inhibited)
222518_at / 0.0003 / 0.0017 / 2.46 / UP / ARFGEF2 / ADP-ribosylation factor guanine nucleotide-exchange factor 2 (brefeldin A-inhibited)
218098_at / 0.0020 / 0.0055 / 1.50 / UP / ARFGEF2 / ADP-ribosylation factor guanine nucleotide-exchange factor 2 (brefeldin A-inhibited)
206177_s_at / 0.0012 / 0.0041 / 3.20 / UP / ARG1 / arginase, liver
222508_s_at / 0.0235 / 0.0236 / 1.58 / UP / ARGLU1 / arginine and glutamate rich 1
207606_s_at / 0.0001 / 0.0008 / 1.76 / UP / ARHGAP12 / Rho GTPase activating protein 12
37577_at / 0.0000 / 0.0003 / 1.54 / UP / ARHGAP19 / Rho GTPase activating protein 19
226576_at / 0.0234 / 0.0236 / 1.65 / UP / ARHGAP26 / Rho GTPase activating protein 26
235635_at / 0.0001 / 0.0010 / 1.63 / UP / ARHGAP5 / Rho GTPase activating protein 5
233849_s_at / 0.0028 / 0.0066 / 1.59 / UP / ARHGAP5 / Rho GTPase activating protein 5
226906_s_at / 0.0282 / 0.0265 / 1.54 / UP / ARHGAP9 / Rho GTPase activating protein 9
210649_s_at / 0.0213 / 0.0221 / 1.74 / UP / ARID1A / AT rich interactive domain 1A (SWI-like)
225181_at / 0.0051 / 0.0094 / 1.61 / UP / ARID1B / AT rich interactive domain 1B (SWI1-like)
1553349_at / 0.0001 / 0.0007 / 1.61 / UP / ARID2 / AT rich interactive domain 2 (ARID, RFX-like)
230141_at / 0.0031 / 0.0069 / 1.75 / UP / ARID4A / AT rich interactive domain 4A (RBP1-like)
223111_x_at / 0.0017 / 0.0049 / 1.62 / UP / ARID4B / AT rich interactive domain 4B (RBP1-like)
212614_at / 0.0001 / 0.0010 / 1.75 / UP / ARID5B / AT rich interactive domain 5B (MRF1-like)
201879_at / 0.0017 / 0.0049 / 2.44 / UP / ARIH1 / ariadne homolog, ubiquitin-conjugating enzyme E2 binding protein, 1 (Drosophila)