Prediction of Outcome of Lupus Nephritis

Study Overview
=================
Brief Summary
-----------------
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.

Detailed Description
-----------------
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 .

Official Title
-----------------
Validation of the Assay of Circulating Antibodies Against Glomerular Neo-autoantigens as a Surrogate Biomarker of the Development of Lupus Nephritis

Conditions
-----------------
Systemic Lupus Erythematosus

Intervention / Treatment
-----------------
* Other: Serum collection


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 4 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Lupus Nephritis<br>Collection of serum at onset and during subsequent follow-up at 6, 12, 24 and 36 months for the dosage of circulating autoantibodies. | Other: Serum collection<br>* 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<br>|
| Incident SLE without nephritis<br>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. | Other: Serum collection<br>* 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<br>|
| Prevalent SLE without nephritis<br>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. | Other: Serum collection<br>* 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<br>|
| Rheumatoid arthritis<br>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. | Other: Serum collection<br>* 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<br>|
| Membranous glomerulonephritis<br>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. | Other: Serum collection<br>* 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<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in Proteinuria at 12, 24 and 36 months | proteinuria measured on a 24-hour urine collection. | 12, 24, 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Renal function | 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 |