Urinary T Cell Biomarker for Prediction in Lupus Nephritis

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Lupus Nephritis
• Intervention / Treatment: Diagnostic test: Flow cytometry analysis of urine samples

• Study Type: Observational
• Enrollment (Anticipated): 79

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 10117
    • Charite - Universitatsmedizin Berlin
• United Kingdom
  • London, United Kingdom, NW3 2QG
    • The Royal Free London

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients at medical wards of Charité Universitätsmedizin Berlin and University College London

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Active lupus nephritis; Patients with proliferative lupus nephritis (Class III and IV)	Diagnostic test: Flow cytometry analysis of urine samples; 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
Control; Patients with systemic lupus erythematodes without lupus nephritis or lupus nephritis I, II or VI	Diagnostic test: Flow cytometry analysis of urine samples; 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Charite University, Berlin, Germany
• Collaborators: Berlin Institute of Health

Publications and helpful links

General Publications

• Enghard P, Rieder C, Kopetschke K, Klocke JR, Undeutsch R, Biesen R, Dragun D, Gollasch M, Schneider U, Aupperle K, Humrich JY, Hiepe F, Backhaus M, Radbruch AH, Burmester GR, Riemekasten G. Urinary CD4 T cells identify SLE patients with proliferative lupus nephritis and can be used to monitor treatment response. Ann Rheum Dis. 2014 Jan;73(1):277-83. doi: 10.1136/annrheumdis-2012-202784. Epub 2013 Mar 8.
• Arazi A, Rao DA, Berthier CC, Davidson A, Liu Y, Hoover PJ, Chicoine A, Eisenhaure TM, Jonsson AH, Li S, Lieb DJ, Zhang F, Slowikowski K, Browne EP, Noma A, Sutherby D, Steelman S, Smilek DE, Tosta P, Apruzzese W, Massarotti E, Dall'Era M, Park M, Kamen DL, Furie RA, Payan-Schober F, Pendergraft WF 3rd, McInnis EA, Buyon JP, Petri MA, Putterman C, Kalunian KC, Woodle ES, Lederer JA, Hildeman DA, Nusbaum C, Raychaudhuri S, Kretzler M, Anolik JH, Brenner MB, Wofsy D, Hacohen N, Diamond B; Accelerating Medicines Partnership in SLE network. The immune cell landscape in kidneys of patients with lupus nephritis. Nat Immunol. 2019 Jul;20(7):902-914. doi: 10.1038/s41590-019-0398-x. Epub 2019 Jun 17. Erratum In: Nat Immunol. 2019 Aug 13;:
• Dolff S, Abdulahad WH, Arends S, van Dijk MC, Limburg PC, Kallenberg CG, Bijl M. Urinary CD8+ T-cell counts discriminate between active and inactive lupus nephritis. Arthritis Res Ther. 2013 Feb 27;15(1):R36. doi: 10.1186/ar4189.
• Kopetschke K, Klocke J, Griessbach AS, Humrich JY, Biesen R, Dragun D, Burmester GR, Enghard P, Riemekasten G. The cellular signature of urinary immune cells in Lupus nephritis: new insights into potential biomarkers. Arthritis Res Ther. 2015 Apr 3;17(1):94. doi: 10.1186/s13075-015-0600-y.

Study record dates

Study Major Dates

• Study Start (Actual): July 30, 2019
• Primary Completion (Anticipated): September 1, 2022
• Study Completion (Anticipated): September 1, 2022

Study Registration Dates

• First Submitted: March 23, 2020
• First Submitted That Met QC Criteria: March 24, 2020
• First Posted (Actual): March 25, 2020

Study Record Updates

• Last Update Posted (Actual): March 9, 2022
• Last Update Submitted That Met QC Criteria: March 8, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: outcome; treatment outcome; prediction; lupus nephritis; glomerulonephritis; flow cytometry; urinary biomarker; systemic lupus erythematodes; urinary effector memory T lymphocytes; non-invasive biomarker; CD4-positive T-lymphocytes/immunology
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Kidney Diseases; Urologic Diseases; Connective Tissue Diseases; Glomerulonephritis; Lupus Erythematosus, Systemic; Nephritis; Lupus Nephritis
• Other Study ID Numbers: SLEFLURINOCYTE

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