Inflammatory profiling of patients with familial amyloid polyneuropathy.
Amyloid
Biomarkers
Cytokines
Familial amyloid polyneuropathy
Transthyretin
Journal
BMC neurology
ISSN: 1471-2377
Titre abrégé: BMC Neurol
Pays: England
ID NLM: 100968555
Informations de publication
Date de publication:
28 Jun 2019
28 Jun 2019
Historique:
received:
03
12
2018
accepted:
18
06
2019
entrez:
30
6
2019
pubmed:
30
6
2019
medline:
23
8
2019
Statut:
epublish
Résumé
Familial amyloid polyneuropathy (FAP) or ATTRv (amyloid TTR variant) amyloidosis is a fatal hereditary disease characterized by the deposition of amyloid fibrils composed of transthyretin (TTR). The current diagnosis of ATTRv relies on genetic identification of TTR mutations and on Congo Red-positive amyloid deposits, which are absent in most ATTRv patients that are asymptomatic or early symptomatic, supporting the need for novel biomarkers to identify patients in earlier disease phases allowing disease control. In an effort to search for new markers for ATTRv, our group searched for nine inflammation markers in ATTRv serum from a cohort of 28 Brazilian ATTRv patients. We found that the levels of six markers were increased (TNF-α, IL-1β, IL-8, IL-33, IFN-β and IL-10), one had decreased levels (IL-12) and two of them were unchanged (IL-6 and cortisol). Interestingly, asymptomatic patients already presented high levels of IL-33, IL-1β and IL-10, suggesting that inflammation may take place before fibril deposition. Our findings shed light on a new, previously unidentified aspect of ATTRv, which might help define new criteria for disease management, as well as provide additional understanding of ATTRv aggressiveness.
Sections du résumé
BACKGROUND
BACKGROUND
Familial amyloid polyneuropathy (FAP) or ATTRv (amyloid TTR variant) amyloidosis is a fatal hereditary disease characterized by the deposition of amyloid fibrils composed of transthyretin (TTR). The current diagnosis of ATTRv relies on genetic identification of TTR mutations and on Congo Red-positive amyloid deposits, which are absent in most ATTRv patients that are asymptomatic or early symptomatic, supporting the need for novel biomarkers to identify patients in earlier disease phases allowing disease control.
METHODS
METHODS
In an effort to search for new markers for ATTRv, our group searched for nine inflammation markers in ATTRv serum from a cohort of 28 Brazilian ATTRv patients.
RESULTS
RESULTS
We found that the levels of six markers were increased (TNF-α, IL-1β, IL-8, IL-33, IFN-β and IL-10), one had decreased levels (IL-12) and two of them were unchanged (IL-6 and cortisol). Interestingly, asymptomatic patients already presented high levels of IL-33, IL-1β and IL-10, suggesting that inflammation may take place before fibril deposition.
CONCLUSIONS
CONCLUSIONS
Our findings shed light on a new, previously unidentified aspect of ATTRv, which might help define new criteria for disease management, as well as provide additional understanding of ATTRv aggressiveness.
Identifiants
pubmed: 31253122
doi: 10.1186/s12883-019-1369-4
pii: 10.1186/s12883-019-1369-4
pmc: PMC6599258
doi:
Substances chimiques
Biomarkers
0
Types de publication
Journal Article
Langues
eng
Pagination
146Références
J Neurol Sci. 1999 Feb 1;163(1):47-52
pubmed: 10223410
Science. 2000 Jan 28;287(5453):664-6
pubmed: 10650002
J Leukoc Biol. 2001 Sep;70(3):439-46
pubmed: 11527994
J Neurosci. 2001 Oct 1;21(19):7576-86
pubmed: 11567048
Biol Res Nurs. 2002 Oct;4(2):92-103
pubmed: 12408215
Arch Neurol. 2002 Nov;59(11):1771-6
pubmed: 12433265
Proc Natl Acad Sci U S A. 2004 Mar 2;101(9):2817-22
pubmed: 14981241
J Immunol. 2004 Sep 15;173(6):4197-206
pubmed: 15356171
FASEB J. 2005 Jan;19(1):124-6
pubmed: 15536164
Cell. 2005 Apr 8;121(1):73-85
pubmed: 15820680
Infect Immun. 2008 May;76(5):2080-9
pubmed: 18332211
J Neurol Neurosurg Psychiatry. 2008 Oct;79(10):1171-9
pubmed: 18356256
Eur J Neurol. 2009 Mar;16(3):337-41
pubmed: 19364362
Proc Natl Acad Sci U S A. 2010 May 25;107(21):9813-8
pubmed: 20439745
Ann Rheum Dis. 2010 Sep;69(9):1697-703
pubmed: 20472598
Liver Transpl. 2010 Dec;16(12):1386-92
pubmed: 21117248
Annu Rev Immunol. 2011;29:71-109
pubmed: 21166540
Biochim Biophys Acta. 2011 May;1813(5):878-88
pubmed: 21296109
Biochemistry. 2011 Dec 27;50(51):11070-83
pubmed: 22091638
Lancet Neurol. 2011 Dec;10(12):1086-97
pubmed: 22094129
J Neurol Neurosurg Psychiatry. 2012 Feb;83(2):152-8
pubmed: 22228785
FASEB J. 2012 Jun;26(6):2283-93
pubmed: 22362898
Ann N Y Acad Sci. 2011 Dec;1243:E1-39
pubmed: 22417140
J Biol Chem. 2012 Oct 26;287(44):37206-18
pubmed: 22918834
Mediators Inflamm. 2012;2012:949157
pubmed: 22933833
Muscle Nerve. 2013 Feb;47(2):157-62
pubmed: 23169427
PLoS Pathog. 2013 Jan;9(1):e1003096
pubmed: 23300453
Appl Clin Genet. 2012 Jun 18;5:37-41
pubmed: 23776379
J Neurol. 2013 Nov;260(11):2802-14
pubmed: 23974642
J Endocrinol. 2013 Oct 28;219(3):195-204
pubmed: 24029730
J Neurol. 2013 Dec;260(12):3093-108
pubmed: 24101130
Front Cell Infect Microbiol. 2013 Nov 12;3:77
pubmed: 24273750
World J Gastroenterol. 2014 Feb 21;20(7):1768-76
pubmed: 24587654
Amyloid. 2014 Sep;21(3):175-84
pubmed: 24918964
J Am Coll Cardiol. 2015 Dec 1;66(21):2451-2466
pubmed: 26610878
Theranostics. 2016 Jul 18;6(11):1792-809
pubmed: 27570551
Cell Metab. 2017 Feb 7;25(2):412-427
pubmed: 28041958
J Community Genet. 2018 Jan;9(1):93-99
pubmed: 29052096