Evaluation of Janus Kinase_3 in Juvenile Onset Systemic Lupus Erythematosus

Evaluation of Janus Kinase_3 Expression in Juvenile Onset Systemic Lupus Erythematosus

One of the best understood mechanisms by which cytokines activate signals, thus eliciting specific responses in target cells, involves enzymes such as Janus kinases (JAKs) and transcriptional factors such as signal transducers and activators of transcription (STATs). For immune mediated diseases, both activating and inactivating mutations of JAKs and STATs may cause abnormalities in immune homeostasis. Polymorphisms of JAK/STAT genes have been linked to susceptibility for rheumatoid arthritis (RA) , systemic lupus erythematosus (SLE), psoriatic arthritis (PA) and inflammatory bowel disease (IBD) .

Janus_kinase 3 expression will be evaluated in the serum and renal tissue of lupus patients during active stage of the disease through this study

Study Overview

• Status: Unknown
• Conditions: Systemic Lupus Erythematosus
• Intervention / Treatment: Procedure: renal biopsy and blood sampling

Detailed Description

Investigators will assess the relationship between the expression of Janus_kinase 3 and the clinical and laboratory parameters of disease activity . Disease activity will be assessed through the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Also, investigators will evaluate the relationship between Janus_ kinase 3 expression and histopathological classes of lupus nephritis according to the 2003 International Society of Nephrology/ Renal Pathology Society (ISN/RPS) classification of lupus nephritis. This will be done through Janus_kinase 3 assessment in the blood and renal tissue of lupus patients.

• Study Type: Observational
• Enrollment (Anticipated): 67

Contacts and Locations

• Study Contact: Name: Enas Mohamed Sayed Ahmed; Phone Number: 01004870406; Email: enasmhmd05@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 7 years to 16 years (Child)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

This will include children and adolescents who fulfill the 2012 Systemic Lupus International Collaborating Clinics (SLICC) classification criteria of systemic lupus erythromatosus during a period of 2 years.

Description

Inclusion Criteria:

• Age younger than 16 years.

  • Active disease stage
  • Patients with biopsy proven lupus nephritis according to ISN/RPS classification criteria of lupus nephritis

Exclusion Criteria:

• Lupus patients in remission.

  • Lupus patients with end stage renal disease.
  • Lupus patients with secondary thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS).
  • patients with moderate or severe infection

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
group study 1; children and adolescents who diagnosed as lupus patients	Procedure: renal biopsy and blood sampling; renal biopsy and blood sampling will be taken from lupus patients for evaluation of Janus-kinase 3
group study 2; age and sex matched healthy children free from any infection with no family history of immunological diseases

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Janus-kinase 3 expression	evaluation of Janus-kinase 3 expression in blood and renal tissue of lupus patients during active stage of disease	within 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
correlation	relationship between Janus- kinase expression and clinical and laboratory parameters of disease activity	2 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
correlation	relationship between Janus-kinase 3 expression and histopathological classification of renal biopsy in lupus nephritis proven patients	2 years

Collaborators and Investigators

• Sponsor: Assiut University

Publications and helpful links

General Publications

• Yamaoka K, Saharinen P, Pesu M, Holt VE 3rd, Silvennoinen O, O'Shea JJ. The Janus kinases (Jaks). Genome Biol. 2004;5(12):253. doi: 10.1186/gb-2004-5-12-253. Epub 2004 Nov 30.
• Remmers EF, Plenge RM, Lee AT, Graham RR, Hom G, Behrens TW, de Bakker PI, Le JM, Lee HS, Batliwalla F, Li W, Masters SL, Booty MG, Carulli JP, Padyukov L, Alfredsson L, Klareskog L, Chen WV, Amos CI, Criswell LA, Seldin MF, Kastner DL, Gregersen PK. STAT4 and the risk of rheumatoid arthritis and systemic lupus erythematosus. N Engl J Med. 2007 Sep 6;357(10):977-86. doi: 10.1056/NEJMoa073003.
• Weening JJ, D'Agati VD, Schwartz MM, Seshan SV, Alpers CE, Appel GB, Balow JE, Bruijn JA, Cook T, Ferrario F, Fogo AB, Ginzler EM, Hebert L, Hill G, Hill P, Jennette JC, Kong NC, Lesavre P, Lockshin M, Looi LM, Makino H, Moura LA, Nagata M. The classification of glomerulonephritis in systemic lupus erythematosus revisited. J Am Soc Nephrol. 2004 Feb;15(2):241-50. doi: 10.1097/01.asn.0000108969.21691.5d. Erratum In: J Am Soc Nephrol. 2004 Mar;15(3):835-6.
• Petri M. Review of classification criteria for systemic lupus erythematosus. Rheum Dis Clin North Am. 2005 May;31(2):245-54, vi. doi: 10.1016/j.rdc.2005.01.009.

Study record dates

Study Major Dates

• Study Start (Anticipated): July 15, 2020
• Primary Completion (Anticipated): July 15, 2021
• Study Completion (Anticipated): July 15, 2022

Study Registration Dates

• First Submitted: February 29, 2020
• First Submitted That Met QC Criteria: February 29, 2020
• First Posted (Actual): March 3, 2020

Study Record Updates

• Last Update Posted (Actual): March 4, 2020
• Last Update Submitted That Met QC Criteria: March 3, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: lupus; active; Janus-kinase3
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Connective Tissue Diseases; Lupus Erythematosus, Systemic
• Other Study ID Numbers: EKNL

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