S100A8 in Serum and Urine as a New Biomarker in Lupus Nephritis

This study aims to evaluate both serum and urine S100A8 as potential biomarkers for Lupus nephritis (LN)

Study Overview

• Status: Completed
• Conditions: Nephritis; Urine; Serum; Lupus; Biomarker; S100A8

Detailed Description

Systemic lupus erythematosus (SLE) is a systemic autoimmune/ inflammatory disease that can affect any organ of the human body. The molecular pathophysiology of SLE remains largely unknown, but complex interactions of genetic factors, the environment, and hormones contribute to disease expression.

Clinical importance of S100 calcium-binding protein A8 protein (S100A8) as a biomarker in SLE has been well-established. During an inflammatory reaction, neutrophils produce S100A8, a Ca2+-binding protein that is part of the S100 family and is found in neutrophil extracellular traps.

In addition to its primary role as a member of the S100A8/A9 heterodimer, S100A8 accumulates in various bodily compartments and functions as a damage-associated molecular pattern molecule upon release. It is a crucial regulator of inflammation and enhances the function of innate immune cells by interacting with members of the immunoglobulin superfamily of cell surface molecules, such as toll-like receptor 4 and the receptor of advanced glycation end products.

Serum S100A8 levels are linked with disease activity, glomerulonephritis, and anti-double-stranded DNA (dsDNA) antibodies (Ab), according to increasing experimental and clinical data. healthy controls (HCs) had lower serum S100A8 levels. Considering that elevated blood S100A8 levels are also seen in several inflammatory disorders such as inflammatory bowel disease and rheumatoid arthritis, it is unclear if this elevated level is adequate to serve as a biomarker specific to SLE.

• Study Type: Observational
• Enrollment (Actual): 70

Contacts and Locations

Study Locations

• Egypt
  • Giza, Egypt, 12411
    • Theodor Bilharz Research Institute

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Participants were stratified into two main groups: Group I consisted of 50 SLE patients, further subdivided into Group IA (n=30) with LN and Group IB (n=20) without LN. Group II comprised 20 age- and sex-matched healthy controls.

Description

Inclusion Criteria:

• Age ≥ 18 years.
• Both sexes.
• Patients with Systemic lupus erythematosus (SLE)
• Patients with SLE and renal affection. SLE diagnosis is based on the 1997 American College of Rheumatology (ACR) criteria or the 2012 Systemic Lupus International Collaborating Clinics (SLICC) classification criteria.

Renal involvement (lupus Nephritis) (LN) can be diagnosed by presence of proteinurea or elevated kidney function and can be confirmed by biopsy if present.

Exclusion Criteria:

• Autoimmune diseases.
• Sjogren's syndrome.
• Rheumatoid arthritis.
• Systemic sclerosis.
• Taking other biologic disease-modifying anti-rheumatic drugs.
• Immunosuppressive drugs.
• Corticosteroid.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Systemic lupus erythematosus (SLE) Group; Systemic lupus erythematosus (SLE) patients. Group I will be subdivided into two groups: Group IA (n=30): SLE patients with lupus nephritis (LN) Group IB (n=20): SLE patients without LN.
Control Group; Age and sex matched healthy control

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of S100A8 levels in serum for diagnosing lupus nephritis (LN)	Venous blood (5cm blood) and urine will be collected from patients with systemic lupus erythematosus (SLE) and healthy control, and the serum will be immediately centrifuged at 15,928 relative centrifugal force (RCF) and for 10 min. The supernatant will be collected and stored at -80°C until further analysis. Before the enzyme-linked immunosorbent assay (ELISA) is conducted, frozen serum samples will be thawed and then diluted 1:100 in phosphate-buffered saline. S100A8 homodimer concentrations will be measured using a commercially available ELISA kit for serum.	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Accessment S100A8 levels in urine for diagnosing lupus nephritis (LN)	Venous blood (5cm blood) and urine will be collected from patients with systemic lupus erythematosus (SLE) and healthy control, and the serum will be immediately centrifuged at 15,928 relative centrifugal force (RCF) and for 10 min. The supernatant will be collected and stored at -80°C until further analysis. Before the enzyme-linked immunosorbent assay (ELISA) is conducted, frozen urine samples will be thawed and then diluted 1:100 in phosphate-buffered saline. S100A8 homodimer concentrations will be measured using a commercially available ELISA kit for urine.	3 months
Correlation between S100A8 level and disease activity markers	Correlation between S100A8 level and disease activity markers in patients with systemic lupus erythematosus will be measured	3 months
Using S100A8 as a predictor for renal affection in systemic lupus erythematosus (SLE) patients for follow up and early treatment.	Renal involvement lupus Nephritis can be diagnosed by presence of proteinurea or elevated kidney function and can be confirmed by biopsy if present.	3 months

Collaborators and Investigators

• Sponsor: Theodor Bilharz Research Institute

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2024
• Primary Completion (Actual): March 30, 2025
• Study Completion (Actual): March 30, 2025

Study Registration Dates

• First Submitted: March 6, 2025
• First Submitted That Met QC Criteria: March 6, 2025
• First Posted (Actual): March 12, 2025

Study Record Updates

• Last Update Posted (Actual): May 21, 2025
• Last Update Submitted That Met QC Criteria: May 18, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Glomerulonephritis; Lupus Erythematosus, Systemic; Nephritis; Lupus Nephritis
• Other Study ID Numbers: PT(882)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The data will be available upon a reasonable request from the corresponding author after the end of study for one year.
• IPD Sharing Time Frame: After the end of study for one year.
• IPD Sharing Access Criteria: The data will be available upon a reasonable request from the corresponding autho
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

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