Prediction of Outcome of Lupus Nephritis
28 juli 2020 uppdaterad av: Gian Marco Ghiggeri MD, PhD, Istituto Giannina Gaslini
Validation of the Assay of Circulating Antibodies Against Glomerular Neo-autoantigens as a Surrogate Biomarker of the Development of Lupus Nephritis
The purpose of this study is to clarify the mechanisms involved in the formation and glomerular deposition of immune complexes in lupus nephritis.
The determination of an antibody pattern specific for systemic lupus erythematosus and lupus nephritis may also have a role in predicting disease progression in patients with systemic lupus erythematosus without renal impairment. As for the patients enrolled in the study, the determination of their antibody patterns may contribute to a more targeted and personalized treatment, allowing a prediction of disease progression and the introduction of early targeted treatments, in order to block the onset and/or progression of renal damage.
Studieöversikt
Status
Okänd
Betingelser
Intervention / Behandling
Detaljerad beskrivning
Prospective multicenter study on the validity of levels of circulating antibodies to glomerular neo-autoantigens (alpha-enolase and annexin AI) and implantable antigens (anti-DNA, histone, istone3, istone4, C1q) as a surrogate biomarker for the diagnosis of lupus nephritis.
The study will involve the collection of serum from patients with lupus nephritis at onset and during subsequent follow-up at 6, 12, 24 and 36 months for the titration of circulating autoantibodies.
As a control the investigators will use the sera of patients with systemic lupus erythematosus without nephropathy, collected at the same time intervals.
The investigators will also assess the antibody positivity in groups of patients with rheumatologic disease similar to lupus (rheumatoid arthritis) and in patients with autoimmune nephropathy without extrarenal clinical signs.
Regarding patients with systemic lupus erythematosus the investigators will collect sera of both incident and prevalent patients in order to monitor changes in antibody levels in conjunction with the development of renal disease.
Clinical tests (renal function, complete blood count, C reactive protein (CRP), ANA, native DNA (nDNA), urine analysis) will be performed at 6, 12, 24 and 36 months and the surplus of blood samples will be used to create the serum bank of the study.
Samples will be collected in the pediatric nephrology of Giannina Gaslini Children Hospital, Genoa (coordinator centre) and in 5 rheumatological (Genoa, Pisa, Pavia, Padova, Brescia) and 6 nephrological (Milan, Genoa, Parma, Brescia, Bologna and Reggio Emilia) italian adults departments .
Studietyp
Observationell
Inskrivning (Förväntat)
800
Kontakter och platser
Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.
Studieorter
-
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Italy/GE
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Genoa, Italy/GE, Italien, 16147
- Rekrytering
- IRCCS Giannina Gaslini Children Hospital
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Kontakt:
- Gian Marco Ghiggeri, MD
- Telefonnummer: 0039 010 5636 2419
- E-post: gmarcoghiggeri@ospedale-gaslini.ge.it
-
Huvudutredare:
- Gian Marco Ghiggeri, MD
-
Underutredare:
- Alice Bonanni, MD
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Deltagandekriterier
Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.
Urvalskriterier
Åldrar som är berättigade till studier
4 år till 65 år (Barn, Vuxen, Äldre vuxen)
Tar emot friska volontärer
Nej
Kön som är behöriga för studier
Allt
Testmetod
Sannolikhetsprov
Studera befolkning
- 250 patients with newly diagnosed lupus nephritis (stage I-VI according to WHO classification). First serum will be collected at the time of renal biopsy (study group).
- 250 patients with incident or prevalent systemic lupus erythematosus (according to ARA criteria) and no signs of nephropathy (control group).
- 50 patients with rheumatoid arthritis (according to ARA criteria), without documented nephropathy (control group)
- 250 patients with histological diagnosis of membranous nephropathy (control group).
Beskrivning
Inclusion Criteria:
- Age between 4 and 65 years
- Diagnosis of lupus nephritis-systemic lupus erythematosus (systemic lupus erythematosus, rheumatoid arthritis and membranous nephropathy for controls)
- Informed consent
Exclusion Criteria:
- Severe infections in place
- Malignancies of any current or history
- Chronic hepatitis B Virus (HBV) or Hepatitis C Virus (HCV) positive
- Breast-feeding or pregnant
- Known hypersensitivity to drugs
Studieplan
Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.
Hur är studien utformad?
Designdetaljer
Kohorter och interventioner
Grupp / Kohort |
Intervention / Behandling |
|---|---|
|
Lupus Nephritis
Collection of serum at onset and during subsequent follow-up at 6, 12, 24 and 36 months for the dosage of circulating autoantibodies.
|
Clinical tests (renal function, complete blood count, CRP, ANA, dsDNA, urinalysis) will be performed at fixed time intervals (6, 12, 24 and 36 months) and the surplus of blood sample will form the serum bank used for the study
|
|
Incident SLE without nephritis
Collection of serum at onset and during subsequent follow-up at 6, 12, 24 and 36 months for the dosage of circulating autoantibodies, in order to evaluate the presence of nephritic manifestations.
|
Clinical tests (renal function, complete blood count, CRP, ANA, dsDNA, urinalysis) will be performed at fixed time intervals (6, 12, 24 and 36 months) and the surplus of blood sample will form the serum bank used for the study
|
|
Prevalent SLE without nephritis
Collection of serum at onset and during subsequent follow-up at 6, 12, 24 and 36 months for the dosage of circulating autoantibodies in order to evaluate the presence of nephritic manifestations.
|
Clinical tests (renal function, complete blood count, CRP, ANA, dsDNA, urinalysis) will be performed at fixed time intervals (6, 12, 24 and 36 months) and the surplus of blood sample will form the serum bank used for the study
|
|
Rheumatoid arthritis
Collection of serum at onset and during subsequent follow-up at 6, 12, 24 and 36 months for the dosage of circulating autoantibodies in order to evaluate the presence of nephritic manifestations.
|
Clinical tests (renal function, complete blood count, CRP, ANA, dsDNA, urinalysis) will be performed at fixed time intervals (6, 12, 24 and 36 months) and the surplus of blood sample will form the serum bank used for the study
|
|
Membranous glomerulonephritis
Collection of serum at onset and during subsequent follow-up at 6, 12, 24 and 36 months for the dosage of circulating autoantibodies in order to exclude secondary forms of the disease.
|
Clinical tests (renal function, complete blood count, CRP, ANA, dsDNA, urinalysis) will be performed at fixed time intervals (6, 12, 24 and 36 months) and the surplus of blood sample will form the serum bank used for the study
|
Vad mäter studien?
Primära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
|---|---|---|
|
Change from baseline in Proteinuria at 12, 24 and 36 months
Tidsram: 12, 24, 36 months
|
proteinuria measured on a 24-hour urine collection.
|
12, 24, 36 months
|
Sekundära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
|---|---|---|
|
Renal function
Tidsram: 36 months
|
estimated glomerular filtration rate (eGFR) measured according to Revised Bedside Schwartz Formula (4-17 years old patients) or CKD-EPI Creatinine 2009 Equation (18-64 years old patients)
|
36 months
|
Samarbetspartners och utredare
Det är här du hittar personer och organisationer som är involverade i denna studie.
Sponsor
Utredare
- Studierektor: Gian Marco Ghiggeri, MD, IRCCS Giannina Gaslini, Genoa
Publikationer och användbara länkar
Den som ansvarar för att lägga in information om studien tillhandahåller frivilligt dessa publikationer. Dessa kan handla om allt som har med studien att göra.
Allmänna publikationer
- Yu C, Gershwin ME, Chang C. Diagnostic criteria for systemic lupus erythematosus: a critical review. J Autoimmun. 2014 Feb-Mar;48-49:10-3. doi: 10.1016/j.jaut.2014.01.004. Epub 2014 Jan 21.
- Cameron JS. Lupus nephritis. J Am Soc Nephrol. 1999 Feb;10(2):413-24. doi: 10.1681/ASN.V102413. No abstract available.
- Madaio MP. The relevance of antigen binding to the pathogenicity of lupus autoantibodies. Kidney Int. 2012 Jul;82(2):125-7. doi: 10.1038/ki.2012.159.
- Waldman M, Madaio MP. Pathogenic autoantibodies in lupus nephritis. Lupus. 2005;14(1):19-24. doi: 10.1191/0961203305lu2054oa.
- Bagavant H, Fu SM. Pathogenesis of kidney disease in systemic lupus erythematosus. Curr Opin Rheumatol. 2009 Sep;21(5):489-94. doi: 10.1097/BOR.0b013e32832efff1.
- Hanrotel-Saliou C, Segalen I, Le Meur Y, Youinou P, Renaudineau Y. Glomerular antibodies in lupus nephritis. Clin Rev Allergy Immunol. 2011 Jun;40(3):151-8. doi: 10.1007/s12016-010-8204-4.
- Kramers C, Hylkema MN, van Bruggen MC, van de Lagemaat R, Dijkman HB, Assmann KJ, Smeenk RJ, Berden JH. Anti-nucleosome antibodies complexed to nucleosomal antigens show anti-DNA reactivity and bind to rat glomerular basement membrane in vivo. J Clin Invest. 1994 Aug;94(2):568-77. doi: 10.1172/JCI117371.
- Bruschi M, Galetti M, Sinico RA, Moroni G, Bonanni A, Radice A, Tincani A, Pratesi F, Migliorini P, Murtas C, Franceschini F, Trezzi B, Brunini F, Gatti R, Tardanico R, Barbano G, Piaggio G, Messa P, Ravani P, Scolari F, Candiano G, Martini A, Allegri L, Ghiggeri GM. Glomerular Autoimmune Multicomponents of Human Lupus Nephritis In Vivo (2): Planted Antigens. J Am Soc Nephrol. 2015 Aug;26(8):1905-24. doi: 10.1681/ASN.2014050493. Epub 2014 Nov 14.
- Bruschi M, Sinico RA, Moroni G, Pratesi F, Migliorini P, Galetti M, Murtas C, Tincani A, Madaio M, Radice A, Franceschini F, Trezzi B, Bianchi L, Giallongo A, Gatti R, Tardanico R, Scaloni A, D'Ambrosio C, Carnevali ML, Messa P, Ravani P, Barbano G, Bianco B, Bonanni A, Scolari F, Martini A, Candiano G, Allegri L, Ghiggeri GM. Glomerular autoimmune multicomponents of human lupus nephritis in vivo: alpha-enolase and annexin AI. J Am Soc Nephrol. 2014 Nov;25(11):2483-98. doi: 10.1681/ASN.2013090987. Epub 2014 May 1.
- Angeletti A, Bruschi M, Moroni G, Sinico RA, Franceschini F, Fredi M, Vaglio A, Cavagna L, Petretto A, Pratesi F, Migliorini P, Locatelli F, Pazzola G, Pesce G, Bagnasco M, Manfredi A, Ramirez GA, Esposito P, Murdaca G, Negrini S, Cipriani L, Trezzi B, Emmi G, Cavazzana I, Binda V, d'Alessandro M, Fenaroli P, Pisani I, Garibotto G, Montecucco C, Santoro D, Scolari F, Volpi S, Mosca M, Tincani A, Candiano G, Prunotto M, Verrina E, Ravelli A, Ghiggeri GM. Second Wave Antibodies in Autoimmune Renal Diseases: The Case of Lupus Nephritis. J Am Soc Nephrol. 2021 Dec 1;32(12):3020-3023. doi: 10.1681/ASN.2021050659. Epub 2021 Dec 1.
- Bruschi M, Moroni G, Sinico RA, Franceschini F, Fredi M, Vaglio A, Cavagna L, Petretto A, Pratesi F, Migliorini P, Manfredi A, Ramirez GA, Esposito P, Negrini S, Trezzi B, Emmi G, Santoro D, Scolari F, Volpi S, Mosca M, Tincani A, Candiano G, Prunotto M, Verrina E, Angeletti A, Ravelli A, Ghiggeri GM. Neutrophil Extracellular Traps in the Autoimmunity Context. Front Med (Lausanne). 2021 Mar 22;8:614829. doi: 10.3389/fmed.2021.614829. eCollection 2021.
- Bruschi M, Moroni G, Sinico RA, Franceschini F, Fredi M, Vaglio A, Cavagna L, Petretto A, Pratesi F, Migliorini P, Locatelli F, Pazzola G, Pesce G, Bagnasco M, Manfredi A, Ramirez GA, Esposito P, Murdaca G, Negrini S, Cipriani L, Trezzi B, Emmi G, Cavazzana I, Binda V, Fenaroli P, Pisani I, Garibotto G, Montecucco C, Santoro D, Scolari F, Mosca M, Tincani A, Candiano G, Prunotto M, Volpi S, Verrina E, Angeletti A, Ravelli A, Ghiggeri GM. Serum IgG2 antibody multicomposition in systemic lupus erythematosus and lupus nephritis (Part 1): cross-sectional analysis. Rheumatology (Oxford). 2021 Jul 1;60(7):3176-3188. doi: 10.1093/rheumatology/keaa767.
- Bruschi M, Moroni G, Sinico RA, Franceschini F, Fredi M, Vaglio A, Cavagna L, Petretto A, Pratesi F, Migliorini P, Locatelli F, Pazzola G, Pesce G, Bagnasco M, Manfredi A, Ramirez GA, Esposito P, Murdaca G, Negrini S, Cipriani L, Trezzi B, Emmi G, Cavazzana I, Binda V, d'Alessandro M, Fenaroli P, Pisani I, Garibotto G, Montecucco C, Santoro D, Scolari F, Volpi S, Mosca M, Tincani A, Candiano G, Prunotto M, Verrina E, Angeletti A, Ravelli A, Ghiggeri GM. Serum IgG2 antibody multi-composition in systemic lupus erythematosus and in lupus nephritis (Part 2): prospective study. Rheumatology (Oxford). 2021 Jul 1;60(7):3388-3397. doi: 10.1093/rheumatology/keaa793.
- Bruschi M, Bonanni A, Petretto A, Vaglio A, Pratesi F, Santucci L, Migliorini P, Bertelli R, Galetti M, Belletti S, Cavagna L, Moroni G, Franceschini F, Fredi M, Pazzola G, Allegri L, Sinico RA, Pesce G, Bagnasco M, Manfredi A, Ramirez GA, Ramoino P, Bianchini P, Puppo F, Pupo F, Negrini S, Mattana F, Emmi G, Garibotto G, Santoro D, Scolari F, Ravelli A, Tincani A, Cravedi P, Volpi S, Candiano G, Ghiggeri GM. Neutrophil Extracellular Traps Profiles in Patients with Incident Systemic Lupus Erythematosus and Lupus Nephritis. J Rheumatol. 2020 Mar;47(3):377-386. doi: 10.3899/jrheum.181232. Epub 2019 May 15.
Studieavstämningsdatum
Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.
Studera stora datum
Studiestart
1 oktober 2014
Primärt slutförande (Förväntat)
1 november 2020
Avslutad studie (Förväntat)
1 november 2022
Studieregistreringsdatum
Först inskickad
23 mars 2015
Först inskickad som uppfyllde QC-kriterierna
25 mars 2015
Första postat (Uppskatta)
31 mars 2015
Uppdateringar av studier
Senaste uppdatering publicerad (Faktisk)
29 juli 2020
Senaste inskickade uppdateringen som uppfyllde QC-kriterierna
28 juli 2020
Senast verifierad
1 juli 2020
Mer information
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Ytterligare relevanta MeSH-villkor
Andra studie-ID-nummer
- SLE1
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