title: Loss of gastric interstitial cells of Cajal in patients with hereditary transthyretin amyloidosis.
abstract: BACKGROUND
  Hereditary transthyretin (TTR) amyloidosis is a systemic neuropathic disorder caused by TTR gene mutations. Gastrointestinal complications are common and the underlying mechanisms remain unclear. The interstitial cells of Cajal (ICC) function as pacemaker cells in the gastrointestinal tract and are important for gastrointestinal motility. The aim of this study was to investigate the densities of gastric ICC and nerves in patients with TTR amyloidosis compared to non-amyloidosis controls.
  
  
  METHODS
  Antral wall autopsy specimens from 11 Japanese ATTR V30M patients and 10 controls were analyzed with immunohistochemistry and computerized analysis. Antibodies to c-Kit and TMEM16A were used to assess ICC and an antibody to PGP 9.5 was used to assess nervous tissue. The study was approved by a Japanese ethical committee.
  
  
  RESULTS
  The densities of c-Kit-immunoreactive (IR) ICC were significantly lower in the circular and longitudinal muscle layers of patients compared to controls (p = 0.004 for both). Equivalent results were found for TMEM16A-IR ICC. There were no significant differences in PGP 9.5-IR cells in the circular or longitudinal muscle layers between patients and controls (p = 0.173 and 0.099, respectively).
  
  
  CONCLUSIONS
  A loss of gastrointestinal ICC may be an important factor for the digestive disturbances in hereditary TTR amyloidosis.
authors: Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden. jonas.wixner@medicin.umu.se
authors: Jonas
authors: J
authors: Wixner
authors: Konen
authors: K
authors: Obayashi
authors: Yukio
authors: Y
authors: Ando
authors: Pontus
authors: P
authors: Karling
authors: Intissar
authors: I
authors: Anan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000682:Amyloid / Q000378:metabolism*; D028227:Amyloid Neuropathies, Familial / Q000378:metabolism / Q000473:pathology*; D000075369:Anoctamin-1; D016022:Case-Control Studies; D018118:Chloride Channels / Q000378:metabolism; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007124:Immunoenzyme Techniques; D056885:Interstitial Cells of Cajal / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009130:Muscle, Smooth / Q000378:metabolism / Q000473:pathology; D009363:Neoplasm Proteins / Q000378:metabolism; D009420:Nervous System / Q000378:metabolism / Q000473:pathology; D011228:Prealbumin / Q000378:metabolism*; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D012737:Sex Factors; D013270:Stomach / Q000473:pathology*
chemical_list: C476213:ANO1 protein, human; D000682:Amyloid; D000075369:Anoctamin-1; D018118:Chloride Channels; D009363:Neoplasm Proteins; D011228:Prealbumin; D019009:Proto-Oncogene Proteins c-kit
references: FEBS Lett. 2001 Jun 8;498(2-3):201-3
references: 11412857
references: Gut. 2010 Dec;59(12):1716-26
references: 20871131
references: Neurogastroenterol Motil. 2008 Jan;20(1):8-18
references: 18173559
references: J Intern Med. 1994 May;235(5):479-85
references: 8182405
references: Biochem Biophys Res Commun. 1997 Mar 17;232(2):497-502
references: 9125209
references: Neurogastroenterol Motil. 2012 Dec;24(12):1111-e568
references: 22897426
references: J Gastroenterol. 2006 Nov;41(11):1076-87
references: 17160518
references: J Support Oncol. 2007 Sep;5(8):355-63
references: 17944143
references: Histochem J. 1997 Mar;29(3):249-56
references: 9472387
references: Scand J Clin Lab Invest. 2001 Feb;61(1):11-8
references: 11300606
references: Eur J Intern Med. 2012 Sep;23(6):499-505
references: 22863425
references: Neurogastroenterol Motil. 2008 May;20 Suppl 1:54-63
references: 18402642
references: J Intern Med. 1999 May;245(5):469-73
references: 10363747
references: Gastroenterology. 2010 Jun;138(7):2399-409, 2409.e1
references: 20178793
references: Am J Physiol Gastrointest Liver Physiol. 2010 Jun;298(6):G1013-9
references: 20378827
references: J Cell Biol. 1969 Jul;42(1):68-91
references: 4891915
references: Clin Pharmacol Ther. 2010 Feb;87(2):187-90
references: 19956091
references: Acta Med Scand Suppl. 1976;590:1-64
references: 1064291
references: J Gastroenterol Hepatol. 2002 Jun;17(6):666-70
references: 12100611
references: Histochem J. 1997 Feb;29(2):177-81
references: 9147074
references: Prog Neurobiol. 2003 Dec;71(5):385-400
references: 14757117
references: Dig Dis Sci. 1996 Oct;41(10):1909-14
references: 8888700
references: J Intern Med. 2003 Sep;254(3):225-35
references: 12930231
references: Clin Genet. 2009 Feb;75(2):163-8
references: 19018796
references: Gut. 1994 Oct;35(10):1413-8
references: 7959197
references: Amyloid. 1999 Jun;6(2):124-9
references: 10439119
references: J Intern Med. 2002 Feb;251(2):136-41
references: 11905589
references: J Neurol Sci. 1987 Jun;79(1-2):129-39
references: 3039063
references: FEBS J. 2007 Apr;274(7):1637-50
references: 17381508
references: Amyloid. 2003 Jun;10(2):121-6
references: 12964420
references: World J Gastroenterol. 2010 Jul 14;16(26):3239-48
references: 20614479
references: Acta Neuropathol. 2001 Sep;102(3):227-32
references: 11585246
references: Amyloid. 1999 Sep;6(3):192-8
references: 10524284
references: Scand J Gastroenterol. 2000 Sep;35(9):985-9
references: 11063162
references: J Intern Med. 1998 Jan;243(1):65-72
references: 9487333
references: Acta Neuropathol. 2002 Nov;104(5):441-7
references: 12410391
references: J Auton Nerv Syst. 1991 Jul;35(1):63-70
references: 1940028
references: J Intern Med. 1991 Jan;229(1):55-9
references: 1899879
references: Acta Neuropathol. 1999 Jul;98(1):48-54
references: 10412800
references: Neurogastroenterol Motil. 2011 Jan;23(1):36-44
references: 20723073
references: Transplantation. 2000 Sep 15;70(5):794-9
references: 11003360