Evaluation of Serum Follistatin-Like Protein 1 Levels in Behcet's Disease and Its Association With Disease Activity

Behçet's disease (BD) is a multi-system auto inflammatory disorder with vasculitic features.

The exact etiological of BD is still obscure, although environmental and genetics factors have been found to be involved in disease pathogenesis.FSTL-1 can act as diagnostic and prognostic biomarkers for Some inflammatory autoimmune diseases including BD.

Study Overview

• Status: Recruiting
• Conditions: Behcet Syndrome
• Intervention / Treatment: Diagnostic test: serum Follistatin-like protein 1

Detailed Description

Behçet's disease (BD) is a multi-system auto inflammatory disorder with vasculitic features Clinical manifestation of BD includes recurrent oral and genital ulcerations, uveitis, skin lesions, vascular, neurological, and gastrointestinal manifestations.The exact etiological of BD is still obscure, although environmental and genetics factors have been found to be involved in disease pathogenesis.

Most of BD manifestations have features of systemic perivasculitis. Cell-mediated immunity has a significant role in BD pathogenesis . Activation of Type 1 helper T (Th1) cell will increase levels of circulating T-lymphocytes, with subsequent increase in the levels of proinflammatory cytokines accounting for most of BD symptoms. These proinflammatory cytokines may be used as an indicator of disease severity. Also Increased macrophage activation, neutrophil chemotaxis, and phagocytosis have been described in BD lesion.

Indeed, the need for studying biomarkers that may drive inflammatory pathways involved in BD pathogenesis is crucial.

Follistatin-like proteins (FLP) belong to the family of acidic cysteine-rich secreted glycoproteins (SPARC) that are highly homologous to the activin-binding protein, follistatin (FST)(7). this group of proteins include five types: FSTL1, FSTL2, FSTL3, FSTL4 and FSTL5.

Follistatin-like protein 1 (FSTL-1) is a soluble gly¬coprotein expressed by mesenchymal cells. It has been involved in various signaling pathways and biological processes. FSTL1 has dual effect in inflammatory processes and has been evaluated in some laboratory models and can serve as pro-inflammatory and anti-inflammatory markers.

During the acute inflammation FSL1 may act as an anti-inflammatory factor, while they exert a pro-inflammatory effect in chronic inflammation. This dual effect has been explained by activation of several signaling pathways.

Although, additional exogenous and endogenous factors, may be involved in such regulation. Increased serum levels FSTL1 levels were found in some of autoimmune systemic diseases including rheumatoid arthritis, Sjogren's syndrome and osteoarthritis. Moreover, the In¬creased serum levels of FSTL-1 where found to be positively correlated with disease activity in some autoim¬mune diseases, including, rheumatoid arthritis (RA), juvenile idiopathic arthritis and systemic lupus ery¬thematosus (SLE).

Based on the above mention findings, FSTL-1 can act as diagnostic and prognostic biomarkers for Some inflammatory autoimmune diseases including BD.

• Study Type: Observational
• Enrollment (Estimated): 76

Contacts and Locations

• Study Contact: Name: Sara Farrag, Lecturer; Phone Number: +201097767735; Email: Sara_farrag@aun.edu.eg
• Study Contact Backup: Name: Eman Mohamed, Lecturer; Phone Number: 01063489998; Email: eman202@aun.edu.eg

Study Locations

• Egypt
  • Assiut, Egypt, 71111
    • Recruiting
    • Assiut University Hospitals
    • Contact: Sara Farrag, Lecturer; Phone Number: +201097767735; Email: Sara_farrag@aun.edu.eg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Adult BD patients who fulfilling the criteria for the diagnosis by International Team for the Revision of the International Criteria for Bechet's Disease

Description

Inclusion Criteria:

• Adult BD patients who fulfilling the criteria for the diagnosis by International Team for the Revision of the International Criteria for Bechet's Disease

Exclusion Criteria:

• Individuals with other autoimmune diseases (rheumatoid arthritis dermatomyositis, scleroderma, mixed connective tissue disease).

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
control group; healthy matched controls	Diagnostic test: serum Follistatin-like protein 1; Serum FSL1 level Test principle The kit uses a double-antibody sandwich enzyme-linked immunosorbent assay(ELISA) to assay the level ofHuman Follistatin Like Protein 1(FSTL1) in samples. Add Follistatin Like Protein 1(FSTL1)to monoclonal antibody.Enzyme well which is pre-coated with Human Follistatin Like Protein1(FSTL1)monoclonal antibody, incubation; then, add Follistatin Like Protein 1(FSTL1)antibodies labeled with biotin, and combined with Streptavidin-HRP to form immune complex; then carry out incubation and washing again to remove the uncombined enzyme. Then add Chromogen Solution A, B, the color of the liquid changes into the blue, And at the effect of acid, the color finally becomes yellow. The chroma of color and the concentration of the Human Substance Follistatin Like Protein 1(FSTL1) of sample were positively correlated.
Behçet's disease; patients with who fulfilling the criteria for the diagnosis by International Team for the Revision of the International Criteria for Bechet's Disease	Diagnostic test: serum Follistatin-like protein 1; Serum FSL1 level Test principle The kit uses a double-antibody sandwich enzyme-linked immunosorbent assay(ELISA) to assay the level ofHuman Follistatin Like Protein 1(FSTL1) in samples. Add Follistatin Like Protein 1(FSTL1)to monoclonal antibody.Enzyme well which is pre-coated with Human Follistatin Like Protein1(FSTL1)monoclonal antibody, incubation; then, add Follistatin Like Protein 1(FSTL1)antibodies labeled with biotin, and combined with Streptavidin-HRP to form immune complex; then carry out incubation and washing again to remove the uncombined enzyme. Then add Chromogen Solution A, B, the color of the liquid changes into the blue, And at the effect of acid, the color finally becomes yellow. The chroma of color and the concentration of the Human Substance Follistatin Like Protein 1(FSTL1) of sample were positively correlated.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
FSL1in the serum of BD patients	the level of FSL1in the serum of BD patients and their relation to various disease clinical and laboratory data in addition to the correlation between FSL1 level and BD activity.	3 months

Collaborators and Investigators

• Sponsor: Assiut University
• Investigators: Principal Investigator: Sara Farrag, Lecturer, Assiut University

Publications and helpful links

General Publications

• Yazici Y, Hatemi G, Bodaghi B, Cheon JH, Suzuki N, Ambrose N, Yazici H. Behcet syndrome. Nat Rev Dis Primers. 2021 Sep 16;7(1):67. doi: 10.1038/s41572-021-00301-1.
• Tortoriello DV, Sidis Y, Holtzman DA, Holmes WE, Schneyer AL. Human follistatin-related protein: a structural homologue of follistatin with nuclear localization. Endocrinology. 2001 Aug;142(8):3426-34. doi: 10.1210/endo.142.8.8319.
• Kaplan H, Calis M, Yazici C, Gunturk I, Cuce I, Senel AS. Are follistatin-like protein 1 and follistatin-like protein 3 associated with inflammatory processes in patients with familial Mediterranean fever? North Clin Istanb. 2023 Jun 6;10(3):306-313. doi: 10.14744/nci.2022.54189. eCollection 2023.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2024
• Primary Completion (Estimated): February 1, 2025
• Study Completion (Estimated): March 1, 2025

Study Registration Dates

• First Submitted: December 9, 2024
• First Submitted That Met QC Criteria: December 9, 2024
• First Posted (Actual): December 12, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 13, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mouth Diseases; Stomatognathic Diseases; Vascular Diseases; Cardiovascular Diseases; Genetic Diseases, Inborn; Eye Diseases; Skin Diseases; Skin Diseases, Vascular; Skin Diseases, Genetic; Uveal Diseases; Vasculitis; Panuveitis; Uveitis, Anterior; Uveitis; Hereditary Autoinflammatory Diseases; Behcet Syndrome
• Other Study ID Numbers: SFA12024

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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