Evidence map›Paper›PMID 36912952›Full record

ArticleArchives of dermatological research2023

Unravelling morphoea aetiopathogenesis by next-generation sequencing of paired skin biopsies.

Amanda M Saracino, Daniel Kelberman, Georg W Otto, Andrey Gagunashvili, David J Abraham, Christopher P Denton

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Archives of dermatological research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed, 1 pooled it
1.0field-weighted citation impact, top 24% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 1 synthesis or guideline pooled it, 4 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 3 countries.

Amanda M SaracinoDivision of Medicine, Centre for Rheumatology and Connective Tissues Diseases, University College London, London, UK. amanda@dramandasaracino.com.au.
Daniel KelbermanGOSgene, Genetics and Genomic Medicine, Great Ormand Street Institute of Child Health, University College London, London, UK.
Georg W OttoGOSgene, Genetics and Genomic Medicine, Great Ormand Street Institute of Child Health, University College London, London, UK.
Andrey GagunashviliGOSgene, Genetics and Genomic Medicine, Great Ormand Street Institute of Child Health, University College London, London, UK.
David J AbrahamDivision of Medicine, Centre for Rheumatology and Connective Tissues Diseases, University College London, London, UK.
Christopher P DentonDivision of Medicine, Centre for Rheumatology and Connective Tissues Diseases, University College London, London, UK.
University College London · GBRoyal Free London NHS Foundation Trust · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMorphoea can have a significant disease burden. Aetiopathogenesis remains poorly understood, with very limited existing genetic studies. Linear morphoea (LM) may follow Blascho's lines of epidermal development, providing potential pathogenic clues.

objectiveThe first objective of this study was to identify the presence of primary somatic epidermal mosaicism in LM. The second objective was tTo explore differential gene expression in morphoea epidermis and dermis to identify potential pathogenic molecular pathways and tissue layer cross-talk. METHODOLOGY: Skin biopsies from paired affected and contralateral unaffected skin were taken from 16 patients with LM. Epidermis and dermis were isolated using a 2-step chemical-physical separation protocol. Whole Genome Sequencing (WGS; n = 4 epidermal) and RNA-seq (n = 5-epidermal, n = 5-dermal) with gene expression analysis via GSEA-MSigDBv6.3 and PANTHER-v14.1 pathway analyses, were performed. RTqPCR and immunohistochemistry were used to replicate key results.

resultsSixteen participants (93.8% female, mean age 27.7 yrs disease-onset) were included. Epidermal WGS identified no single affected gene or SNV. However, many potential disease-relevant pathogenic variants were present, including ADAMTSL1 and ADAMTS16. A highly proliferative, inflammatory and profibrotic epidermis was seen, with significantly-overexpressed TNFα-via-NFkB, TGFβ, IL6/JAKSTAT and IFN-signaling, apoptosis, p53 and KRAS-responses. Upregulated IFI27 and downregulated LAMA4 potentially represent initiating epidermal 'damage' signals and enhanced epidermal-dermal communication. Morphoea dermis exhibited significant profibrotic, B-cell and IFN-signatures, and upregulated morphogenic patterning pathways such as Wnt.

conclusionThis study supports the absence of somatic epidermal mosaicism in LM, and identifies potential disease-driving epidermal mechanisms, epidermal-dermal interactions and disease-specific dermal differential-gene-expression in morphoea. We propose a potential molecular narrative for morphoea aetiopathogenesis which could help guide future targeted studies and therapies.

Indexed as

Scleroderma, LocalizedAdultBiopsyEpidermisFemaleHumansMaleRNA-SeqSkinAetiopathogenesisGene expressionGenomicsLinear morphoeaLocalised sclerodermaMorphoeaNext-generation sequencingTranscriptomics

Identifiers

PMID36912952
PMCPMC10366313
OpenAlexW4324020195

What OpenQuestion holds

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LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.