Analysis of Cytokine Expression Pattern in Systemic Sclerosis (SCLEROKINE)

Analysis of Cytokine Expression Pattern in Systemic Sclerosis: Study of the Role of Interleukine-34

By contrast to other proinflammatory cytokines which are found up-regulated in the skin of patients with psoriasis, atopic dermatitis or systemic sclerosis, IL-34 is the only cytokine that undergoes down-regulation. This finding is interesting regarding the description of IL-34 as an immunosuppressive cytokine. In this study, the expression and the role of interleukin-34 (IL-34) will be investigated in the physiopathology of systemic sclerosis.

Study Overview

• Status: Completed
• Conditions: Systemic Sclerosis
• Intervention / Treatment: Procedure: Skin biopsies

Detailed Description

The mechanisms involved in the physiopathology of systemic sclerosis (SSc) are not fully understood, particularly the pattern of cytokine expression in the skin of SSc patients. These cytokines are known to play a central role in the regulation of numerous inflammatory diseases and, among them, IL-34 is the only cytokine which has been found to be down-regulated in other skin inflammatory disorders such psoriasis or atopic dermatitis. IL-34 has been described as an immunosuppressive cytokine, and our preliminary results show that IL-34 is active on fibroblasts, a key cell that undergoes dysfunction in SSc. Thus, we are willing to explore its expression profile in the skin of SSc patients and its potential role in the physiopathology of the disease. For this study, we will analyze IL-34 mRNA levels in the skin and the plasma of SSc patients by comparison to healthy patients. Thirty patients will be included in the Internal Medicine Unit of the CHU de Poitiers during a single visit, in the frame of their medical follow-up, to collect two skin biopsies and 5 ml of blood after obtaining their informed consent. The expression of IL-34 will also be investigated at the protein level by immunostaining on skin sections and by ELISA (skin protein lysates and plasma). Moreover, the expression of other proinflammatory cytokines will be investigated both at the mRNA and protein levels.

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Poitiers, France
    • CHU de Poitiers

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age ≥ 18 year-old
• Diagnosis of systemic sclerosis according to ACR/EURAL 2013 criteria.
• Skin sclerosis reaching an area over finger bases of hands and feet
• Free subject, without neither guardianship, wardship nor subordination
• Patient with Social Security
• Informed and signed consent by the patient after clear and loyal information on the study

Exclusion Criteria:

• Age < 18 year-old
• Patients that do not fit the ACR/EURAL 2013 criteria
• Patients under immunosuppressive treatment
• Sclerosis limited to fingers of hands and feets.
• Patient without Social Security
• Pregnant and nursing women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sclerodermic patients; Sclerodermic patients presenting cutaneous fibrosis	Procedure: Skin biopsies; Two skin biopsies (4mm punch) are performed under local anesthesia at the site of cutaneous inflammation/fibrosis.; Other Names: Serum collection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Skin IL-34 mRNA expression levels	Skin IL-34 mRNA expression levels (expressed in % of relative expression of GAPDH) in systemic sclerosis patients by comparison with healthy subjects. Skin biopsies are collected at D0 for SSc patients (inclusion day)	1 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immunostainings against IL-34 and other cytokines on skin sections	Immunostainings against IL-34 and other cytokines on skin sections from systemic sclerosis patients versus healthy skins	1 day
Protein expression levels of IL-34 and other cytokines by ELISA	Protein expression levels of IL-34 and other cytokines by ELISA (quantitative study) in plasma and lysates of skin biopsies from systemic sclerosis patients versus	1 day
Skin IL-34 mRNA expression levels of other cytokines	Skin IL-34 mRNA expression levels of other cytokines in patients with systemic sclerosis compared to healthy patients.	1 day

Collaborators and Investigators

• Sponsor: Poitiers University Hospital
• Collaborators: University of Poitiers
• Investigators: Study Director: Jean-François Jégou, PhD, University of Poitiers

Study record dates

Study Major Dates

• Study Start (Actual): July 12, 2018
• Primary Completion (Actual): September 4, 2019
• Study Completion (Actual): September 4, 2019

Study Registration Dates

• First Submitted: May 15, 2018
• First Submitted That Met QC Criteria: May 15, 2018
• First Posted (Actual): May 25, 2018

Study Record Updates

• Last Update Posted (Actual): April 21, 2020
• Last Update Submitted That Met QC Criteria: April 20, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: cytokine; skin inflammation
• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Connective Tissue Diseases; Sclerosis; Scleroderma, Systemic; Scleroderma, Diffuse
• Other Study ID Numbers: SCLEROKINE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No