Urinary T Cell Biomarker for Prediction in Lupus Nephritis

Study Overview
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Brief Summary
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Urinary T-lymphocytes may be predictive for clinical outcome in patients with lupus nephritis. The investigators hypothesize that the amount of CD4+ effector/memory T-cells in urine at time of diagnosis predicts the outcome of patients with active lupus nephritis (LN) after 6 months of therapy. In a prospective, six-months follow-up study patients' urine will be analysed by flow cytometry every 60 days (+/- 10d). Treatment will be performed to the discretion of the treating clinician. After 6 months of treatment response will be determined as either complete response or partial response.

Official Title
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Phenotype of Urinary CD4+ T Cells as Biomarkers for Prediction of Outcome in Lupus Nephritis

Conditions
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Lupus Nephritis

Intervention / Treatment
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* Diagnostic Test: Flow cytometry analysis of urine samples


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Biopsy proven lupus nephritis In absence of a biopsy a SLEDAI of at least 10 & at least two renal elements of the renal SLEDAI (rSLEDAI) Informed consent Diagnosis of SLE according to the American College of Rheumatology (ACR) criteria Exclusion Criteria: Biopsy-proven non-SLE related disease Urinary tract infection Active menstrual bleeding Kidney transplantation during observation time

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active lupus nephritis<br>Patients with proliferative lupus nephritis (Class III and IV) | Diagnostic Test: Flow cytometry analysis of urine samples<br>* Urine samples will be conserved and frozen upon arrival. All samples will be stained according to T cell and TEC (tubular epithelial cells) panel with fluorochromes. T cell panel: CD3, CD4, CD8, CCR7, CD45RO, CD28, CD279; TEC panel: vimentin, cytokeratine, CD10, CD13, CD227, CD326<br>|
| Control<br>Patients with systemic lupus erythematodes without lupus nephritis or lupus nephritis I, II or VI | Diagnostic Test: Flow cytometry analysis of urine samples<br>* Urine samples will be conserved and frozen upon arrival. All samples will be stained according to T cell and TEC (tubular epithelial cells) panel with fluorochromes. T cell panel: CD3, CD4, CD8, CCR7, CD45RO, CD28, CD279; TEC panel: vimentin, cytokeratine, CD10, CD13, CD227, CD326<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phenotype of CD4+ T cells at time point 0 predictive of clinical outcome in patients with lupus nephritis | Urinary CD4+ effector/memory T cell counts at time point 0 (time of diagnosis) predict clinical outcome (complete or partial response) after 6 months of treatment in patients with lupus nephritis. The frequency of effector/memory CD4+ T lymphocytes is higher in patients with non- or partial response. Complete response at 24 weeks: the return to within 10 percent of normal values of serum creatinine levels, proteinuria, and urine sediment. Partial response at 24 weeks: improvement of 50 percent in all abnormal renal measurements, without worsening - within 10 percent - of any measurement | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Distinction between proliferative LN (class III and class IV) and non-proliferative LN (classes I, II and VI) |  | 6 months | 
| Analysis of patient with persistent renal abnormalities as partial response |  | 6 months | 
| Prediction of complete or partial response according to normalization of the amount of urinary T cells at time point 2 and 4 |  | 6 months | 
| Phenotype of CD8+ T cells at time point 0 predictive of clinical outcome in patients with lupus nephritis | Urinary CD8+ effector/memory T cell counts at time point 0 (time of diagnosis) predict clinical outcome (complete or partial response) after 6 months of treatment in patients with lupus nephritis. The frequency of effector/memory CD8+ T lymphocytes is higher in patients with non- or partial response. | 6 months | 
| Diagnosis of proliferative lupus nephritis in patients with systemic lupus erythematodes (SLE) | Diagnosis according to initial T cell count | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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lupus nephritis, systemic lupus erythematodes, urinary biomarker, outcome, prediction, urinary effector memory T lymphocytes, glomerulonephritis, non-invasive biomarker, flow cytometry, treatment outcome, CD4-positive T-lymphocytes/immunology