Multicenter Intestinal Current Measurements in Rectal Biopsies from CF and Non-CF Subjects to Monitor CFTR Function

被引:40
作者
Clancy, John P. [1 ,2 ]
Szczesniak, Rhonda D. [1 ,2 ]
Ashlock, Melissa A. [3 ]
Ernst, Sarah E. [4 ]
Fan, Lijuan [5 ]
Hornick, Douglas B. [4 ]
Karp, Philip H. [4 ]
Khan, Umer [6 ]
Lymp, James [7 ]
Ostmann, Alicia J. [1 ,2 ]
Rezayat, Amir [1 ,2 ]
Starner, Timothy D. [8 ]
Sugandha, Shajan P. [9 ]
Sun, Hongtao [1 ,2 ]
Quinney, Nancy [10 ]
Donaldson, Scott H. [10 ]
Rowe, Steven M. [9 ]
Gabriel, Sherif E. [11 ]
机构
[1] Cincinnati Childrens Hosp Med Ctr, Dept Pediat, Cincinnati, OH 45229 USA
[2] Univ Cincinnati, Cincinnati, OH USA
[3] Cyst Fibrosis Fdn, Bethesda, MD USA
[4] Univ Iowa, Dept Internal Med, Iowa City, IA 52242 USA
[5] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA
[6] Seattle Childrens Hosp, Dept Biostat, Seattle, WA USA
[7] Genentech Inc, San Francisco, CA 94080 USA
[8] Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA
[9] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA
[10] Univ N Carolina, Dept Med, Chapel Hill, NC USA
[11] N30 Pharmaceut, Aurora, CO USA
来源
PLOS ONE | 2013年 / 8卷 / 09期
基金
美国国家卫生研究院;
关键词
NASAL POTENTIAL DIFFERENCE; CYSTIC-FIBROSIS GENE; DELTA-F508 HOMOZYGOUS TWINS; BIOAVAILABLE COMPOUND; STOP MUTATION; CONDUCTANCE; IDENTIFICATION; PATHOGENESIS; SUPPRESSION; EXPRESSION;
D O I
10.1371/journal.pone.0073905
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Intestinal current measurements (ICM) from rectal biopsies are a sensitive means to detect cystic fibrosis transmembrane conductance regulator (CFTR) function, but have not been optimized for multicenter use. We piloted multicenter standard operating procedures (SOPs) to detect CFTR activity by ICM and examined key questions for use in clinical trials. SOPs for ICM using human rectal biopsies were developed across three centers and used to characterize ion transport from non-CF and CF subjects (two severe CFTR mutations). All data were centrally evaluated by a blinded interpreter. SOPs were then used across four centers to examine the effect of cold storage on CFTR currents and compare CFTR currents in biopsies from one subject studied simultaneously either at two sites (24 hours post-biopsy) or when biopsies were obtained by either forceps or suction. Rectal biopsies from 44 non-CF and 17 CF subjects were analyzed. Mean differences (mu A/cm(2); 95% confidence intervals) between CF and non-CF were forskolin/IBMX=102.6(128.0 to 81.1), carbachol=96.3(118.7 to 73.9), forskolin/IBMX+carbachol=200.9(243.1 to 158.6), and bumetanide=-44.6 (-33.7 to -55.6) (P<0.005, CF vs non-CF for all parameters). Receiver Operating Characteristic curves indicated that each parameter discriminated CF from non-CF subjects (area under the curve of 0.94-0.98). CFTR dependent currents following 18-24 hours of cold storage for forskolin/IBMX, carbachol, and forskolin/IBMX+carbachol stimulation (n=17 non-CF subjects) were 44%, 47.5%, and 47.3%, respectively of those in fresh biopsies. CFTR-dependent currents from biopsies studied after cold storage at two sites simultaneously demonstrated moderate correlation (n=14 non-CF subjects, Pearson correlation coefficients 0.389, 0.484, and 0.533). Similar CFTR dependent currents were detected from fresh biopsies obtained by either forceps or suction (within-subject comparisons, n=22 biopsies from three non-CF subjects). Multicenter ICM is a feasible CFTR outcome measure that discriminates CF from non-CF ion transport, offers unique advantages over other CFTR bioassays, and warrants further development as a potential CFTR biomarker.
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页数:13
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共 56 条
  • [1] Effect of VX-770 in Persons with Cystic Fibrosis and the G551D-CFTR Mutation
    Accurso, Frank J.
    Rowe, Steven M.
    Clancy, J. P.
    Boyle, Michael P.
    Dunitz, Jordan M.
    Durie, Peter R.
    Sagel, Scott D.
    Hornick, Douglas B.
    Konstan, Michael W.
    Donaldson, Scott H.
    Moss, Richard B.
    Pilewski, Joseph M.
    Rubenstein, Ronald C.
    Uluer, Ahmet Z.
    Aitken, Moira L.
    Freedman, Steven D.
    Rose, Lynn M.
    Mayer-Hamblett, Nicole
    Dong, Qunming
    Zha, Jiuhong
    Stone, Anne J.
    Olson, Eric R.
    Ordonez, Claudia L.
    Campbell, Preston W.
    Ashlock, Melissa A.
    Ramsey, Bonnie W.
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 2010, 363 (21) : 1991 - 2003
  • [2] Use of nasal potential difference and sweat chloride as outcome measures in multicenter clinical trials in subjects with cystic fibrosis
    Ahrens, RC
    Standaert, TA
    Launspach, J
    Han, SH
    Teresi, ME
    Aitken, ML
    Kelley, TJ
    Hilliard, KA
    Milgram, LJH
    Konstan, MW
    Weatherly, MR
    McCarty, NA
    [J]. PEDIATRIC PULMONOLOGY, 2002, 33 (02) : 142 - 150
  • [3] Assessment of CFTR function in native epithelia for the diagnosis of cystic fibrosis
    Barreto, C
    Mall, M
    Amaral, MD
    [J]. PEDIATRIC PULMONOLOGY, 2004, : 243 - 243
  • [4] INTRACLASS CORRELATION COEFFICIENT AS A MEASURE OF RELIABILITY
    BARTKO, JJ
    [J]. PSYCHOLOGICAL REPORTS, 1966, 19 (01) : 3 - &
  • [5] Improved oxygenation promotes CFTR maturation and trafficking in MDCK monolayers
    Bebök, Z
    Tousson, A
    Schwiebert, LM
    Venglarik, CJ
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, 2001, 280 (01): : C135 - C145
  • [6] STATISTICAL METHODS FOR ASSESSING AGREEMENT BETWEEN TWO METHODS OF CLINICAL MEASUREMENT
    BLAND, JM
    ALTMAN, DG
    [J]. LANCET, 1986, 1 (8476) : 307 - 310
  • [7] New concepts of the pathogenesis of cystic fibrosis lung disease
    Boucher, RC
    [J]. EUROPEAN RESPIRATORY JOURNAL, 2004, 23 (01) : 146 - 158
  • [8] An overview of the pathogenesis of cystic fibrosis lung disease
    Boucher, RC
    [J]. ADVANCED DRUG DELIVERY REVIEWS, 2002, 54 (11) : 1359 - 1371
  • [9] Airway surface dehydration in cystic fibrosis: Pathogenesis and therapy
    Boucher, Richard C.
    [J]. ANNUAL REVIEW OF MEDICINE, 2007, 58 : 157 - 170
  • [10] Bronsveld I, 2001, J CLIN INVEST, V108, P1705