Differential expression of interferon-induced genes and other tissue-based biomarkers in acute graft-versus-host disease vs. lupus erythematosus in skin.
Acute Disease
Adult
Aged
Aged, 80 and over
Cytokines
/ metabolism
Female
Gene Expression
/ genetics
Graft vs Host Disease
/ metabolism
Humans
Interferons
/ genetics
Lupus Erythematosus, Systemic
/ metabolism
Male
Middle Aged
Reverse Transcriptase Polymerase Chain Reaction
/ methods
Skin Diseases
/ pathology
Journal
Clinical and experimental dermatology
ISSN: 1365-2230
Titre abrégé: Clin Exp Dermatol
Pays: England
ID NLM: 7606847
Informations de publication
Date de publication:
Jun 2019
Jun 2019
Historique:
accepted:
21
04
2018
pubmed:
4
10
2018
medline:
7
1
2020
entrez:
4
10
2018
Statut:
ppublish
Résumé
In both acute graft-versus-host disease (GVHD) and lupus erythematosus (LE), the patient's own tissues are subjected to immunological assault via complex mechanisms influenced by interferon (IFN) and other cytokines. Although not typically confused clinically, these entities have overlapping histopathological findings in the skin. To assess whether GVHD can be differentiated from LE using molecular methods on skin specimens. We developed a quantitative reverse transcription PCR assay based on previously identified tissue-based biomarkers of cutaneous GVHD, and compared gene expression in GVHD with that in LE. Both entities showed robust expression of IFN-induced genes and of genes encoding proteins involved in antigen presentation, cell signalling and tissue repair. Levels of gene expression differed significantly in GVHD compared with LE, particularly those of IFN-induced genes such as MX1, OAS3, TAP1 and STAT3 (P < 0.01). Three logistic regression models could differentiate the two entities with a high degree of certainty (receiver operating characteristic area under the curve of 1.0). The study demonstrates the feasibility of distinguishing between microscopically similar inflammatory dermatoses using tissue-based molecular techniques.
Sections du résumé
BACKGROUND
BACKGROUND
In both acute graft-versus-host disease (GVHD) and lupus erythematosus (LE), the patient's own tissues are subjected to immunological assault via complex mechanisms influenced by interferon (IFN) and other cytokines. Although not typically confused clinically, these entities have overlapping histopathological findings in the skin.
AIM
OBJECTIVE
To assess whether GVHD can be differentiated from LE using molecular methods on skin specimens.
METHODS
METHODS
We developed a quantitative reverse transcription PCR assay based on previously identified tissue-based biomarkers of cutaneous GVHD, and compared gene expression in GVHD with that in LE.
RESULTS
RESULTS
Both entities showed robust expression of IFN-induced genes and of genes encoding proteins involved in antigen presentation, cell signalling and tissue repair. Levels of gene expression differed significantly in GVHD compared with LE, particularly those of IFN-induced genes such as MX1, OAS3, TAP1 and STAT3 (P < 0.01). Three logistic regression models could differentiate the two entities with a high degree of certainty (receiver operating characteristic area under the curve of 1.0).
CONCLUSION
CONCLUSIONS
The study demonstrates the feasibility of distinguishing between microscopically similar inflammatory dermatoses using tissue-based molecular techniques.
Identifiants
pubmed: 30280423
doi: 10.1111/ced.13759
pmc: PMC6445793
mid: NIHMS988500
doi:
Substances chimiques
Cytokines
0
Interferons
9008-11-1
Types de publication
Comparative Study
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e81-e88Subventions
Organisme : NCATS NIH HHS
ID : KL2 TR002379
Pays : United States
Organisme : Department of Dermatology at Mayo Clinic
Organisme : NCI NIH HHS
ID : K08 CA215105
Pays : United States
Organisme : NCI NIH HHS
ID : K08 CA215105
Pays : United States
Organisme : Dermatology Foundation Dermatopathology Career Development Award
Informations de copyright
© 2018 British Association of Dermatologists.
Références
Am J Pathol. 2001 Jul;159(1):237-43
pubmed: 11438470
Proc Natl Acad Sci U S A. 2003 Mar 4;100(5):2610-5
pubmed: 12604793
Blood. 2003 Jul 15;102(2):763-71
pubmed: 12663442
Int J Hematol. 2003 Oct;78(3):181-7
pubmed: 14604275
Br J Dermatol. 2004 Mar;150(3):504-10
pubmed: 15030334
Proc Natl Acad Sci U S A. 2004 May 25;101(21):8120-5
pubmed: 15148407
J Invest Dermatol. 2008 Oct;128(10):2392-402
pubmed: 18418411
Lupus. 2008 Jun;17(6):591-5
pubmed: 18539715
Lupus. 2009 Aug;18(9):858
pubmed: 19578114
Blood. 2011 Sep 22;118(12):3399-409
pubmed: 21719602
Br J Dermatol. 2012 May;166(5):971-5
pubmed: 22242767
Autoimmune Dis. 2012;2012:728605
pubmed: 23091704
Immunol Rev. 2014 Mar;258(1):30-44
pubmed: 24517424
J Cutan Pathol. 2015 Jan;42(1):39-45
pubmed: 25393781
Cytokine. 2015 Jun;73(2):326-34
pubmed: 25767072
J Clin Oncol. 2015 Aug 10;33(23):2509-15
pubmed: 26150443
Oncogene. 2016 Jun 2;35(22):2842-51
pubmed: 26364610
Inflammation. 2016 Jun;39(3):1268-73
pubmed: 27032396
Curr Opin Rheumatol. 2017 Mar;29(2):178-186
pubmed: 28118202
Arthritis Res Ther. 2017 Jun 15;19(1):139
pubmed: 28619037
J Cutan Pathol. 2017 Dec;44(12):1087-1091
pubmed: 28906023
Transplant Proc. 1974 Dec;6(4):367-71
pubmed: 4155153
J Dermatol. 1996 May;23(5):305-9
pubmed: 8675818