Proteome study of cutaneous lupus erythematosus (CLE) and dermatomyositis skin lesions reveals IL-16 is differentially upregulated in CLE.
Complement
Cutaneous lupus erythematosus
Cytokine
Dermatomyositis
Interferon
Systemic lupus erythematosus
Journal
Arthritis research & therapy
ISSN: 1478-6362
Titre abrégé: Arthritis Res Ther
Pays: England
ID NLM: 101154438
Informations de publication
Date de publication:
30 04 2021
30 04 2021
Historique:
received:
10
01
2021
accepted:
12
04
2021
entrez:
1
5
2021
pubmed:
2
5
2021
medline:
22
6
2021
Statut:
epublish
Résumé
The objective of the study was to explore the disease pathways activated in the inflammatory foci of skin lesions in cutaneous lupus erythematosus (CLE) and dermatomyositis (DM). Skin biopsies acquired from active CLE and DM lesions, patient (PC), and also healthy controls (HC) were investigated. Biopsy sections were examined by a pathologist, inflammatory foci were laser micro-dissected and captured, and proteins within captured tissue were detected in an unbiased manner by mass spectrometry. Protein pathway analysis was performed by the string-db.org platform. Findings of interest were confirmed by immunohistochemistry (IHC). Proteome investigation identified abundant expression of interferon-regulated proteins (IRP) as a common feature of CLE and DM. Interleukin (IL)-16 was the only abundant cytokine differentially expressed in CLE compared to DM. Caspase-3, an enzyme that cleaves IL-16 into its active form, was detected in low levels. Significantly higher proportion of IL-16- and caspase-3-positive cells was identified in CLE lesions in comparison with DM, PC, and HC. Proteomic results indicate more abundant complement deposition in CLE skin lesions. Using unbiased mass spectrometry investigation of CLE and DM inflammatory infiltrates, we confirmed that high IRP expression is a common feature of both CLE and DM, while IL-16 is the only differentially expressed cytokine in CLE. IHC confirmed high expression of IL-16 and caspase-3 in CLE. Our novel molecular findings indicate that IL-16 detection could be useful in differential diagnostics between the two conditions that can display similar histopathological appearance. IL-16 could be of interest as a future therapeutic target for CLE.
Sections du résumé
BACKGROUND
The objective of the study was to explore the disease pathways activated in the inflammatory foci of skin lesions in cutaneous lupus erythematosus (CLE) and dermatomyositis (DM).
METHODS
Skin biopsies acquired from active CLE and DM lesions, patient (PC), and also healthy controls (HC) were investigated. Biopsy sections were examined by a pathologist, inflammatory foci were laser micro-dissected and captured, and proteins within captured tissue were detected in an unbiased manner by mass spectrometry. Protein pathway analysis was performed by the string-db.org platform. Findings of interest were confirmed by immunohistochemistry (IHC).
RESULTS
Proteome investigation identified abundant expression of interferon-regulated proteins (IRP) as a common feature of CLE and DM. Interleukin (IL)-16 was the only abundant cytokine differentially expressed in CLE compared to DM. Caspase-3, an enzyme that cleaves IL-16 into its active form, was detected in low levels. Significantly higher proportion of IL-16- and caspase-3-positive cells was identified in CLE lesions in comparison with DM, PC, and HC. Proteomic results indicate more abundant complement deposition in CLE skin lesions.
CONCLUSIONS
Using unbiased mass spectrometry investigation of CLE and DM inflammatory infiltrates, we confirmed that high IRP expression is a common feature of both CLE and DM, while IL-16 is the only differentially expressed cytokine in CLE. IHC confirmed high expression of IL-16 and caspase-3 in CLE. Our novel molecular findings indicate that IL-16 detection could be useful in differential diagnostics between the two conditions that can display similar histopathological appearance. IL-16 could be of interest as a future therapeutic target for CLE.
Identifiants
pubmed: 33931094
doi: 10.1186/s13075-021-02511-0
pii: 10.1186/s13075-021-02511-0
pmc: PMC8086067
doi:
Substances chimiques
Il16 protein, human
0
Interleukin-16
0
Proteome
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
132Subventions
Organisme : NIAMS NIH HHS
ID : R01 AR057781
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR065964
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA015083
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR060861
Pays : United States
Organisme : NCI NIH HHS
ID : K08 CA215105
Pays : United States
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