EVALUATION OF THE PROTEOMIC PROFILE OF PATIENTS WITH ADULT AND JUVENILE LUPUS NEPHRITIS DURING IMMUNOSUPPRESSIVE THERAPY

• Grant number: 24/05036-8
• Support Opportunities: Regular Research Grants
• Start date: April 01, 2025
• End date: March 31, 2028
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Luciana Martins de Carvalho
• Grantee: Luciana Martins de Carvalho
• Host Institution: Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da USP (HCMRP). Secretaria da Saúde (São Paulo - Estado). Ribeirão Preto , SP, Brazil
• Associated researchers: Camila Barbosa Lyra de Oliveira ; Camilla Albertina Dantas de Lima ; Gisele Vajgel Fernandes ; Lucila Maria Valente ; Paula Sandrin Garcia ; Virginia Paes Leme Ferriani

Abstract

Title: EVALUATION OF THE PROTEOMIC PROFILE OF PATIENTS WITH ADULT AND JUVENILE LUPUS NEPHRITIS DURING IMMUNOSUPPRESSIVE THERAPYLupus Nephritis (LN) has a prevalence of approximately 60% in patients with Systemic Lupus Erythematosus (SLE) and represents an important cause of morbidity/mortality in this group of patients. The search for biomarkers to help monitor the response to treatment and follow-up of these patients has been remarkable in recent years, but kidney biopsy, with all its challenges, is still the gold standard for this purpose. Proteomics represents a promising strategy to assist in diagnosis, prognosis, and response to treatment, making it possible to: distinguish histological classes and characteristics of renal biopsies, identify early LN recurrence, correlate with LN activity and chronicity, assist in prognosis and therapeutic response and enable clinical trials with new therapeutic targets.Objectives: To evaluate the proteomic profile of patients with active lupus nephritis during the treatment with immunosuppressants.a) Evaluate the protein expression profile in plasma and urine in patients with adult and juvenile lupus nephritis (cSLE), in activity and sequentially after induction treatment;b) Compare protein expression between LN histological subclasses, activity markers, and histopathological activity index;c) Compare the protein expression profile with findings in the initial and subsequent biopsies, if performed routinely in the service;d) Compare the protein expression profile in kidney biopsies (initial and subsequent, if performed routinely at the service), plasma and, urine to establish the efficiency of using body fluids as markers of renal activity and predictors of response to immunosuppressive treatment.Methodology: Prospective cohort study, to be carried out at the Hospital das Clínicas of the Federal University of Pernambuco (HC-UFPE) and Hospital das Clínicas of the Faculty of Medicine of Ribeirão Preto (FMRP/USP). Twenty patients with adult LN from the glomerulopathies outpatient clinic of HC/UFPE and ten patients with childhood-onset LN from the pediatric rheumatology outpatient clinics of the Hospitals das Clínicas of UFPE and FMRP/USP will be included in the study and will have blood and urine samples collected for proteomic analyses. cSLE will be defined as lupus with onset before 18 years of age. Patients diagnosed with lupus according to the ACR/EULAR 2019 criteria and lupus nephritis confirmed by histological classes defined according to the International Societies of Nephrology and Pathology (ISN/RPS) by renal biopsy (class III-V) will be included. For serum analysis, serum levels of components C3 and C4 and the anti-double-stranded DNA antibody, anti-C1q will be evaluated. In the longitudinal evaluation, we will correlate protein expression with the initial activity and clinical profile of adult and childhood-onset LN, at the time of biopsy and after six, twelve and, eighteen months. The project will be submitted to the Health Ethics Committees of the participating institutions, and patients and their legal guardians, after acceptance, will sign the terms of consent and assent after approval, following the guidelines of the Declaration of Helsinki. The kidney biopsy tissue used in the study will be obtained from a sample of material collected for routine patient treatment and monitoring. The proteomic analysis will be carried out following international protocols.Expected Results: We hypothesize that longitudinal measurement in protein expression in patients during the treatment, will indicate whether patients have persistent inflammation or whether the disease has been effectively controlled. In this way, we hope that the protein profile obtained at different treatment intervals will provide us with evidence about the presence or absence of activity in the renal parenchyma, without the need for invasive and risky procedures such as renal biopsy. (AU)