NCF Gene & TNFSF4 in SLE Patients

System; Lupus Erythematosus Clinical Trial

Official title:

Polymorphisms of the Tumor Necrosis Factor Superfamily 4 and Neutrophil Cytosolic Factor Gene in SLE Egyptian Patients.

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05314881
• Other study ID #: gene polymorphism in SLE
• Status: Not yet recruiting
• Phase: N/A
• Start date: April 1, 2022
• Est. completion date: July 2022

Study information

• Verified date: April 2022
• Source: Assiut University
• Contact: Yasmine Makarem, Dr
• Phone: +201002929015
• Email: yasmine.saad[@]aun.edu.eg
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

the investigators objective is to identify the association of SNP polymorphisms in the TNFS4, and NCF gene and SLE Egyptian patients.

Description:

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by clinical heterogeneity with variable severity. Among the SLE patients, two may share the same clinical manifestations but have different phenotypes.

This is why studies are searching for the different genes that might be associated with SLE susceptibility.

The Neutrophil cytosolic factor (NCF) Gene provide the instruction for the synthesis of group of proteins that form the NADPH oxidase enzyme complex, that is critical for the induction of reactive oxygen species (ROS) which in turn is important in the regulation of immune system.

While the Tumor necrosis factor superfamily 4 (TNFSF4) encodes the ligand for OX40 (OX40L), which delivers a strong costimulatory signal to activated effector T-cells and enhances both Th1 and Th2 responses when engaged with its receptor. Therefore, increased levels of cell surface OX40L may augment B cell differentiation and proliferation. The consequence of which is that the resulting autoantibodies and immune complexes cause disease pathology in SLE.

So, NCF and TNFSF4 gene polymorphism are supposed to be associated with SLE risk and pathophysiology.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 65
• Est. completion date: July 2022
• Est. primary completion date: June 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• SLE patients

• patients older than 18 years old

Exclusion Criteria:

• patients with other connective tissue diseases

• patients older than 70 years old

Related Conditions & MeSH terms

• Lupus Erythematosus, Systemic
• System; Lupus Erythematosus

Intervention

Genetic:
• TNFS4, NCF gene
study the gene polymorphisms from the blood sample of the included SLE patients

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Assiut University

References & Publications (9)

Aziz MM, Galal MAA, Elzohri MH, El-Nouby F, Leong KP. Cross-cultural adaptation and validation of Systemic Lupus Erythematosus Quality of Life questionnaire into Arabic. Lupus. 2018 Apr;27(5):780-787. doi: 10.1177/0961203317747714. Epub 2018 Jan 7. — View Citation

Croft M. The role of TNF superfamily members in T-cell function and diseases. Nat Rev Immunol. 2009 Apr;9(4):271-85. doi: 10.1038/nri2526. Review. — View Citation

Holmdahl R, Sareila O, Olsson LM, Bäckdahl L, Wing K. Ncf1 polymorphism reveals oxidative regulation of autoimmune chronic inflammation. Immunol Rev. 2016 Jan;269(1):228-47. doi: 10.1111/imr.12378. Review. — View Citation

Ito T, Wang YH, Duramad O, Hanabuchi S, Perng OA, Gilliet M, Qin FX, Liu YJ. OX40 ligand shuts down IL-10-producing regulatory T cells. Proc Natl Acad Sci U S A. 2006 Aug 29;103(35):13138-43. Epub 2006 Aug 21. — View Citation

Kaiser R, Criswell LA. Genetics research in systemic lupus erythematosus for clinicians: methodology, progress, and controversies. Curr Opin Rheumatol. 2010 Mar;22(2):119-25. doi: 10.1097/BOR.0b013e3283361943. Review. — View Citation

Lane P. Role of OX40 signals in coordinating CD4 T cell selection, migration, and cytokine differentiation in T helper (Th)1 and Th2 cells. J Exp Med. 2000 Jan 17;191(2):201-6. Review. — View Citation

Lu MM, Xu WD, Yang J, Ye QL, Feng CC, Li J, Pan HF, Tao JH, Wang J, Ye DQ. Association of TNFSF4 polymorphisms with systemic lupus erythematosus: a meta-analysis. Mod Rheumatol. 2013 Jul;23(4):686-93. doi: 10.1007/s10165-012-0708-8. Epub 2012 Aug 1. — View Citation

Olsson LM, Johansson ÅC, Gullstrand B, Jönsen A, Saevarsdottir S, Rönnblom L, Leonard D, Wetterö J, Sjöwall C, Svenungsson E, Gunnarsson I, Bengtsson AA, Holmdahl R. A single nucleotide polymorphism in the NCF1 gene leading to reduced oxidative burst is associated with systemic lupus erythematosus. Ann Rheum Dis. 2017 Sep;76(9):1607-1613. doi: 10.1136/annrheumdis-2017-211287. Epub 2017 Jun 12. — View Citation

Stüber E, Neurath M, Calderhead D, Fell HP, Strober W. Cross-linking of OX40 ligand, a member of the TNF/NGF cytokine family, induces proliferation and differentiation in murine splenic B cells. Immunity. 1995 May;2(5):507-21. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Concentration of gene polymorphism of the TNFS4 & NCF in SLE Egyptian patients.	Identify the number of Participants with SNP polymorphisms in the TNFS4, and NCF gene in SLE Egyptian patients and the relation between the concentration of polymorphism and disease activity	3 months