Autophagy in Systemic Lupus Erythematosus

Systemic Lupus Erythematosus Clinical Trial

Official title:

Autophagy Genes and Interleukin-10 in Systemic Lupus Erythematosus Patients

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03583853
• Other study ID #: amkmm
• Status: Not yet recruiting
• Start date: July 1, 2019
• Est. completion date: December 1, 2020

Study information

• Verified date: July 2018
• Source: Assiut University
• Contact: Mohamed Ali el-feky, prof
• Phone: 00201223971310
• Email: mohelfeky[@]hotmail.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Systemic lupus erythematosus is systemic autoimmune disease characterized by a wide range of clinical manifestations, from skin and mucosal lesions to severe injuries in the central nervous system, kidneys and other organs. The presence of high titres of autoantibodies against nuclear components, immune complexes deposition, complement deficiency and lymphocytes infiltration in affected tissues, which causes tissue and organ damage are the main characteristics of the disease. Nowadays, many studies elucidate the essential role of autophagy in the occurrence, development and severity of systemic lupus erythematosus.

Description:

Autophagy is a highly conserved lysosome-mediated catabolic process. It can remove unwanted cytoplasmic components, such as long-lived and/or misfolded proteins, damaged organelles, playing an important role in maintaining cellular homeostasis and cell survival in stress conditions, such as nutrient deprivation and hypoxia.

Recently, Autophagy is implicated in nearly all steps of both innate and adaptive immune responses, including neutrophil extracellular trap and inflammasome formation, pathogen recognition, lymphocyte and monocyte development and function, antigen processing and presentation, type I interferon production and inflammatory regulation, thus playing an important part in maintaining the balance of immune system.

Autophagy is divided into three major types: macroautophagy, microautophagy, and chaperone-mediated autophagy, with macroautophagy being the most investigated and understood. Disturbances in autophagy have been implicated in chronic inflammatory diseases and several autoimmune diseases, including Systemic lupus erythematosus, multiple sclerosis, Crohn's disease and rheumatoid arthritis.

Several regulatory factors that may play key roles in autophagy processes have been discovered in recent years, such as beclin1, which is the key regulatory factor in the autophagy startup process, microtubule-associated protein-light chain 3, autophagy-related gene 5, which are components of autophagosomes.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 100
• Est. completion date: December 1, 2020
• Est. primary completion date: July 1, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

• patients who fulfilled at least four criteria of systemic lupus erythematosus according to American College of Rheumatology

Exclusion Criteria:

• Pregnancy or lactation.

• coexistence of other autoimmune diseases.

Related Conditions & MeSH terms

• Lupus Erythematosus, Systemic
• Systemic Lupus Erythematosus

Intervention

Device:
• real time PCR
real time PCR will be used for determination of expression of autophagy genes

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Assiut University

References & Publications (10)

Ciccacci C, Perricone C, Alessandri C, Latini A, Politi C, Delunardo F, Pierdominici M, Conti F, Novelli G, Ortona E, Borgiani P. Evaluation of ATG5 polymorphisms in Italian patients with systemic lupus erythematosus: contribution to disease susceptibility and clinical phenotypes. Lupus. 2018 Jan 1:961203318776108. doi: 10.1177/0961203318776108. [Epub ahead of print] — View Citation

Dang J, Li J, Xin Q, Shan S, Bian X, Yuan Q, Liu N, Ma X, Li Y, Liu Q. Gene-gene interaction of ATG5, ATG7, BLK and BANK1 in systemic lupus erythematosus. Int J Rheum Dis. 2016 Dec;19(12):1284-1293. doi: 10.1111/1756-185X.12768. Epub 2015 Sep 30. — View Citation

Godsell J, Rudloff I, Kandane-Rathnayake R, Hoi A, Nold MF, Morand EF, Harris J. Clinical associations of IL-10 and IL-37 in systemic lupus erythematosus. Sci Rep. 2016 Oct 6;6:34604. doi: 10.1038/srep34604. — View Citation

Klionsky DJ. Autophagy: from phenomenology to molecular understanding in less than a decade. Nat Rev Mol Cell Biol. 2007 Nov;8(11):931-7. Review. — View Citation

López P, Alonso-Pérez E, Rodríguez-Carrio J, Suárez A. Influence of Atg5 mutation in SLE depends on functional IL-10 genotype. PLoS One. 2013 Oct 18;8(10):e78756. doi: 10.1371/journal.pone.0078756. eCollection 2013. — View Citation

Teruel M, Alarcón-Riquelme ME. The genetic basis of systemic lupus erythematosus: What are the risk factors and what have we learned. J Autoimmun. 2016 Nov;74:161-175. doi: 10.1016/j.jaut.2016.08.001. Epub 2016 Aug 10. Review. — View Citation

Ward MM, Marx AS, Barry NN. Comparison of the validity and sensitivity to change of 5 activity indices in systemic lupus erythematosus. J Rheumatol. 2000 Mar;27(3):664-70. — View Citation

Zhang Y, Morgan MJ, Chen K, Choksi S, Liu ZG. Induction of autophagy is essential for monocyte-macrophage differentiation. Blood. 2012 Mar 22;119(12):2895-905. doi: 10.1182/blood-2011-08-372383. Epub 2012 Jan 5. — View Citation

Zhou XJ, Lu XL, Lv JC, Yang HZ, Qin LX, Zhao MH, Su Y, Li ZG, Zhang H. Genetic association of PRDM1-ATG5 intergenic region and autophagy with systemic lupus erythematosus in a Chinese population. Ann Rheum Dis. 2011 Jul;70(7):1330-7. doi: 10.1136/ard.2010.140111. — View Citation

Zhu L, Wang H, Wu Y, He Z, Qin Y, Shen Q. The Autophagy Level Is Increased in the Synovial Tissues of Patients with Active Rheumatoid Arthritis and Is Correlated with Disease Severity. Mediators Inflamm. 2017;2017:7623145. doi: 10.1155/2017/7623145. Epub 2017 Feb 1. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in the expression of autophagy genes in systemic lupus erythematosus patients group and control group	the expression of autophagy genes will be measured by real time polymerase chain reaction	Baseline and 6 months