Evidence map›Paper›PMID 27208972›Full record

Trial reportArthritis research & therapy2016

B cell depletion therapy upregulates Dkk-1 skin expression in patients with systemic sclerosis: association with enhanced resolution of skin fibrosis.

Dimitrios Daoussis, Athanassios Tsamandas, Ioannis Antonopoulos, Alexandra Filippopoulou, Dionysios J Papachristou, Nicholaos I Papachristou, Andrew P Andonopoulos, Stamatis-Nick Liossis

Open access · goldAbstract readRandomized Controlled Trial
In one paragraph

Trial report in Arthritis research & therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed, 1 pooled it
2.2field-weighted citation impact, top 13% 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

24 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Review
  5. Review
  6. Fibrosis-the tale of H3K27 histone methyltransferases and demethylases.Frontiers in cell and developmental biology · 2023
    Review
  7. Review
  8. Review
  9. Review
  10. Review
  11. Review
  12. Article
  13. Article
  14. Rehabilitation of the face and temporomandibular joint in systemic sclerosis.Therapeutic advances in musculoskeletal disease · 2021
    Article
  15. The Roles of Immune Cells in the Pathogenesis of Fibrosis.International journal of molecular sciences · 2020
    Review
  16. Review
  17. Review
  18. Article
  19. Article
  20. 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

8 authors at 1 institution in 1 country.

Dimitrios DaoussisDivision of Rheumatology, Department of Internal Medicine, Patras University Hospital, University of Patras Medical School, Rion, Patras, 26504, Greece. jimdaoussis@hotmail.com.
Athanassios TsamandasDepartment of Patholology, Patras University Hospital, University of Patras Medical School, Patras, Greece.
Ioannis AntonopoulosDivision of Rheumatology, Department of Internal Medicine, Patras University Hospital, University of Patras Medical School, Rion, Patras, 26504, Greece.
Alexandra FilippopoulouDivision of Rheumatology, Department of Internal Medicine, Patras University Hospital, University of Patras Medical School, Rion, Patras, 26504, Greece.
Dionysios J PapachristouDepartment of Anatomy-Histology-Embryology, Laboratory of Bone and Soft Tissue Studies, University of Patras Medical School, Patras, Greece.
Nicholaos I PapachristouDepartment of Anatomy-Histology-Embryology, Laboratory of Bone and Soft Tissue Studies, University of Patras Medical School, Patras, Greece.
Andrew P AndonopoulosDivision of Rheumatology, Department of Internal Medicine, Patras University Hospital, University of Patras Medical School, Rion, Patras, 26504, Greece.
Stamatis-Nick LiossisDivision of Rheumatology, Department of Internal Medicine, Patras University Hospital, University of Patras Medical School, Rion, Patras, 26504, Greece.
University of Patras · GR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundRituximab (RTX) may favorably affect skin and lung fibrosis in patients with systemic sclerosis (SSc); however, the underlying molecular mechanisms remain unknown. We aimed to explore the hypothesis that RTX may mediate its antifibrotic effects by regulating the expression of Dickkopf-1 (Dkk-1), an inhibitor of the Wnt pathway.

methodsFourteen patients with SSc and five healthy subjects were recruited. Dkk-1 expression was immunohistochemically assessed in skin biopsies obtained from 11 patients with SSc (8 treated with RTX and 3 with standard treatment), whereas DKK1 gene expression was assessed in 3 patients prior to and following RTX administration.

resultsIn baseline biopsies obtained from all patients with SSc but not in healthy subjects, Dkk-1 was undetectable in skin fibroblasts. Following RTX treatment, four out of eight patients had obvious upregulation of Dkk-1 skin expression. Similarly, RTX treatment correlated with a significant 4.8-fold upregulation of DKK1 gene expression (p = 0.030). In contrast, TGFβ expression in the upper dermis was significantly attenuated following treatment. Moreover, this decreased expression of TGFβ in the skin was significantly more pronounced in the subgroup of patients with Dkk-1 upregulation. In this subgroup TGFβ was downregulated by 50.88 % in contrast to only 15.98 % in patients who did not have Dkk-1 upregulation (p = 0.022).

conclusionsThis is the first study demonstrating a link between B cell depletion and skin Dkk-1 upregulation in patients with SSc. RTX-mediated B cell depletion may mechanistically function via the recently established TGFβ-Dkk-1 axis in improving skin fibrosis.

Indexed as

AdultFemaleFibroblastsFibrosisHumansImmunoassayImmunohistochemistryImmunologic FactorsIntercellular Signaling Peptides and ProteinsLymphocyte DepletionMaleMiddle AgedRituximabScleroderma, SystemicSkinTransforming Growth Factor betaDKK1 protein, humanImmunologic FactorsIntercellular Signaling Peptides and ProteinsRituximabTransforming Growth Factor betaB cell depletionDickkopf-1Dkk-1FibrosisRituximabSclerodermaSkinSystemic sclerosisTGFβ

Identifiers

PMID27208972
PMCPMC4875588
OpenAlexW2397597082

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.