[논문]A Little CFTR Goes a Long Way: CFTR-Dependent Sweat Secretion from G551D and R117H-5T Cystic Fibrosis Subjects Taking Ivacaftor

Char, Jessica E.; Wolfe, Marlene H.; Cho, Hyung-ju; Park, Il-Ho; Jeong, Jin Hyeok; Frisbee, Eric; Dunn, Colleen; Davies, Zoe; Milla, Carlos; Moss, Richard B.; Thomas, Ewart A. C.; Wine, Jeffrey J.

doi:10.1371/journal.pone.0088564

[해외논문] A Little CFTR Goes a Long Way: CFTR-Dependent Sweat Secretion from G551D and R117H-5T Cystic Fibrosis Subjects Taking Ivacaftor 원문보기

PloS one, v.9 no.2, 2014년, pp.e88564 -

Char, Jessica E. (Cystic Fibrosis Research Laboratory, Stanford University, Stanford, California, United States of America) , Wolfe, Marlene H. (Cystic Fibrosis Research Laboratory, Stanford University, Stanford, California, United States of America) , Cho, Hyung-ju (Cystic Fibrosis Research Laboratory, Stanford University, Stanford, California, United States of America) , Park, Il-Ho (Cystic Fibrosis Research Laboratory, Stanford University, Stanford, California, United States of America) , Jeong, Jin Hyeok (Cystic Fibrosis Research Laboratory, Stanford University, Stanford, California, United States of America) , Frisbee, Eric (Cystic Fibrosis Research Laboratory, Stanford University, Stanford, California, United States of America) , Dunn, Colleen (Department of Pediatrics, Stanford University School of Medicine, Stanford, California, United States of America) , Davies, Zoe (Department of Pediatrics, Stanford University School of Medicine, Stanford, California, United States of America) , Milla, Carlos (Department of Pediatrics, Stanford University School of Medicine, Stanford, California, United States of America) , Moss, Richard B. (Department of) , Thomas, Ewart A. C. , Wine, Jeffrey J.

Abstract ▼ AI-Helper

To determine if oral dosing with the CFTR-potentiator ivacaftor (VX-770, Kalydeco) improves CFTR-dependent sweating in CF subjects carrying G551D or R117H-5T mutations, we optically measured sweat secretion from 32–143 individually identified glands in each of 8 CF subjects; 6 F508del/G551D, one G551D/R117H-5T, and one I507del/R117H-5T. Two subjects were tested only (−) ivacaftor, 3 only (+) ivacaftor and 3 (+/−) ivacaftor (1–5 tests per condition). The total number of gland measurements was 852 (−) ivacaftor and 906 (+) ivacaftor. A healthy control was tested 4 times (51 glands). For each gland we measured both CFTR-independent (M-sweat) and CFTR-dependent (C-sweat); C-sweat was stimulated with a β-adrenergic cocktail that elevated [cAMP]i while blocking muscarinic receptors. Absent ivacaftor, almost all CF glands produced M-sweat on all tests, but only 1/593 glands produced C-sweat (10 tests, 5 subjects). By contrast, 6/6 subjects (113/342 glands) produced C-sweat in the (+) ivacaftor condition, but with large inter-subject differences; 3–74% of glands responded with C/M sweat ratios 0.04%–2.57% of the average WT ratio of 0.265. Sweat volume losses cause proportionally larger underestimates of CFTR function at lower sweat rates. The losses were reduced by measuring C/M ratios in 12 glands from each subject that had the highest M-sweat rates. Remaining losses were estimated from single channel data and used to correct the C/M ratios, giving estimates of CFTR function (+) ivacaftor = 1.6%–7.7% of the WT average. These estimates are in accord with single channel data and transcript analysis, and suggest that significant clinical benefit can be produced by low levels of CFTR function.

참고문헌 (38)

1 Sosnay PR, Siklosi KR, Van Goor F, Kaniecki K, Yu H, et al .. (2013) Defining the disease liability of variants in the cystic fibrosis transmembrane conductance regulator gene. Nat Genet.
2 Yu H , Burton B , Huang CJ , Worley J , Cao D , et al ( 2012 ) Ivacaftor potentiation of multiple CFTR channels with gating mutations . Journal of cystic fibrosis: official journal of the European Cystic Fibrosis Society 11 : 237 – 245 . 22293084

상세보기
3 Van Goor F , Hadida S , Grootenhuis PD , Burton B , Cao D , et al ( 2009 ) Rescue of CF airway epithelial cell function in vitro by a CFTR potentiator, VX-770 . Proc Natl Acad Sci U S A 106 : 18825 – 18830 . 19846789

상세보기
4 Accurso FJ , Rowe SM , Clancy JP , Boyle MP , Dunitz JM , et al ( 2010 ) Effect of VX-770 in persons with cystic fibrosis and the G551D-CFTR mutation . N Engl J Med 363 : 1991 – 2003 . 21083385

상세보기
5 Ramsey BW , Davies J , McElvaney NG , Tullis E , Bell SC , et al ( 2011 ) A CFTR potentiator in patients with cystic fibrosis and the G551D mutation . The New England journal of medicine 365 : 1663 – 1672 . 22047557

상세보기
6 Van Goor F , Yu H , Burton B , Huang C , Hoffman B ( 2012 ) Ivacaftor potentiates multiple mutant cystic fibrosis transconductance regulator (CFTR) forms . Pediatr Pulmonol 47 : 233 . 21905268
7 Drumm ML , Konstan MW , Schluchter MD , Handler A , Pace R , et al ( 2005 ) Genetic modifiers of lung disease in cystic fibrosis . N Engl J Med 353 : 1443 – 1453 . 16207846

상세보기
8 Guo X , Pace RG , Stonebraker JR , Commander CW , Dang AT , et al ( 2011 ) Mucin variable number tandem repeat polymorphisms and severity of cystic fibrosis lung disease: significant association with MUC5AC . PLoS One 6 : e25452 . 21998660

상세보기
9 Veeze HJ , Halley DJ , Bijman J , de Jongste JC , de Jonge HR , et al ( 1994 ) Determinants of mild clinical symptoms in cystic fibrosis patients. Residual chloride secretion measured in rectal biopsies in relation to the genotype . The Journal of clinical investigation 93 : 461 – 466 . 8113384

상세보기
10 Wine JJ , Char JE , Chen J , Cho HJ , Dunn C , et al ( 2013 ) In Vivo Readout of CFTR Function: Ratiometric Measurement of CFTR-Dependent Secretion by Individual, Identifiable Human Sweat Glands . PLoS One 8 : e77114 . 24204751

상세보기
11 Farber S ( 1945 ) Some organic digestive disturbances in early life . J Mich Med Soc 44 : 587 .
12 Sheppard DN , Rich DP , Ostedgaard LS , Gregory RJ , Smith AE , et al ( 1993 ) Mutations in CFTR associated with mild-disease-form Cl- channels with altered pore properties . Nature 362 : 160 – 164 . 7680769

상세보기
13 Chu CS , Trapnell BC , Curristin S , Cutting GR , Crystal RG ( 1993 ) Genetic basis of variable exon 9 skipping in cystic fibrosis transmembrane conductance regulator mRNA . Nat Genet 3 : 151 – 156 . 7684646

상세보기
14 Jih KY , Hwang TC ( 2013 ) Vx-770 potentiates CFTR function by promoting decoupling between the gating cycle and ATP hydrolysis cycle . Proc Natl Acad Sci U S A 110 : 4404 – 4409 . 23440202

상세보기
15 Bompadre SG , Sohma Y , Li M , Hwang TC ( 2007 ) G551D and G1349D, two CF-associated mutations in the signature sequences of CFTR, exhibit distinct gating defects . J Gen Physiol 129 : 285 – 298 . 17353351

상세보기
16 Cooke RE , Gochberg SH ( 1956 ) Physiology of the sweat gland in cystic fibrosis of the pancreas . Pediatrics 18 : 701 – 715 . 13370235

상세보기
17 Bijman J , Quinton PM ( 1984 ) Influence of abnormal Cl- impermeability on sweating in cystic fibrosis . Am J Physiol 247 : C3 – 9 . 6331184
18 Cheng SH , Gregory RJ , Marshall J , Paul S , Souza DW , et al ( 1990 ) Defective intracellular transport and processing of CFTR is the molecular basis of most cystic fibrosis . Cell 63 : 827 – 834 . 1699669

상세보기
19 Champigny G , Imler JL , Puchelle E , Dalemans W , Gribkoff V , et al ( 1995 ) A change in gating mode leading to increased intrinsic Cl- channel activity compensates for defective processing in a cystic fibrosis mutant corresponding to a mild form of the disease . EMBO J 14 : 2417 – 2423 . 7540133

상세보기
20 Friedman KJ , Heim RA , Knowles MR , Silverman LM ( 1997 ) Rapid characterization of the variable length polythymidine tract in the cystic fibrosis (CFTR) gene: association of the 5T allele with selected CFTR mutations and its incidence in atypical sinopulmonary disease . Hum Mutat 10 : 108 – 115 . 9259194
21 Cuppens H , Lin W , Jaspers M , Costes B , Teng H , et al ( 1998 ) Polyvariant mutant cystic fibrosis transmembrane conductance regulator genes. The polymorphic (Tg)m locus explains the partial penetrance of the T5 polymorphism as a disease mutation . J Clin Invest 101 : 487 – 496 . 9435322

상세보기
22 Behm JK , Hagiwara G , Lewiston NJ , Quinton PM , Wine JJ ( 1987 ) Hyposecretion of beta-adrenergically induced sweating in cystic fibrosis heterozygotes . Pediatr Res 22 : 271 – 276 . 2889182
23 de Nooijer RA , Nobel JM , Arets HG , Bot AG , van Berkhout FT , et al ( 2011 ) Assessment of CFTR function in homozygous R117H-7T subjects . J Cyst Fibros 10 : 326 – 332 . 21507732
24 Wilschanski M , Zielenski J , Markiewicz D , Tsui LC , Corey M , et al ( 1995 ) Correlation of sweat chloride concentration with classes of the cystic fibrosis transmembrane conductance regulator gene mutations . J Pediatr 127 : 705 – 710 . 7472820

상세보기
25 Taylor CJ , Baxter PS , Hardcastle J , Hardcastle PT ( 1988 ) Failure to induce secretion in jejunal biopsies from children with cystic fibrosis . Gut 29 : 957 – 962 . 2840366

상세보기
26 Berschneider HM , Knowles MR , Azizkhan RG , Boucher RC , Tobey NA , et al ( 1988 ) Altered intestinal chloride transport in cystic fibrosis . Faseb J 2 : 2625 – 2629 . 2838365

상세보기
27 Bijman J , Veeze H , Kansen M , Tilly B , Scholte B , et al ( 1991 ) Chloride transport in the cystic fibrosis enterocyte . Adv Exp Med Biol 290 : 287 – 294 discussion 294–286. 1719765
28 Salinas D , Haggie PM , Thiagarajah JR , Song Y , Rosbe K , et al ( 2005 ) Submucosal gland dysfunction as a primary defect in cystic fibrosis . Faseb J 19 : 431 – 433 . 15596485

상세보기
29 Joo NS , Cho HJ , Khansaheb M , Wine JJ ( 2010 ) Hyposecretion of fluid from tracheal submucosal glands of CFTR-deficient pigs . J Clin Invest 120 : 3161 – 3166 . 20739758

상세보기
30 Cho HJ , Joo NS , Wine JJ ( 2011 ) Defective fluid secretion from submucosal glands of nasal turbinates from CFTR−/− and CFTR (DeltaF508/DeltaF508) pigs . PloS one 6 : e24424 . 21935358
31 Sun X , Sui H , Fisher JT , Yan Z , Liu X , et al ( 2010 ) Disease phenotype of a ferret CFTR-knockout model of cystic fibrosis . J Clin Invest 120 : 3149 – 3160 . 20739752

상세보기
32 Billet A, Luo Y, Balghi H, Hanrahan JW (2013) Role of tyrosine phosphorylation in the muscarinic activation of the Cystic Fibrosis Transmembrane conductance Regulator (CFTR). J Biol Chem.
33 Namkung W , Finkbeiner WE , Verkman AS ( 2010 ) CFTR-adenylyl cyclase I association responsible for UTP activation of CFTR in well-differentiated primary human bronchial cell cultures . Mol Biol Cell 21 : 2639 – 2648 . 20554763
34 Rochon J ( 1990 ) A statistical model for the “N-of-1” study . Journal of clinical epidemiology 43 : 499 – 508 . 2139111

상세보기
35 Spiegelhalter DJ (1988) Statistical issues in studies of individual response. Scandinavian journal of gastroenterology Supplement 147: 40–45.
36 Barlow DH, Hersen M (1984) Single Case Experimental Designs MA, USA: Allyn and Bacon.
37 Kazdin AE (1982) Single-Case Research Designs: Methods for Clinical and Applied Settings. New York, USA: Oxford University Press.
38 Gonska T , Choi P , Stephenson A , Ellis L , Martin S , et al ( 2012 ) Role of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) in patients with chronic sinopulmonary disease . Chest 142 : 996 – 1004 . 22423042

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[해외논문] A Little CFTR Goes a Long Way: CFTR-Dependent Sweat Secretion from G551D and R117H-5T Cystic Fibrosis Subjects Taking Ivacaftor 원문보기

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