Pediatric SLE includes monogenic forms, some of which involve the interferon type I (IFN-I) pathway. The IFN-I pathway is renally active in adult SLE and correlates with the extent of renal damage. In pediatric SLE, and particularly in lupus nephritis, activation of the IFN-I pathway has never been studied, nor is it known whether monogenic forms underlie more pronounced interferon activation.
Pediatric systemic lupus erythematosus (SLE) (cSLE), compared with adult SLE, is characterized by a more severe phenotype, with more marked hematologic, neuropsychiatric, and renal changes. Lupus nephritis is a pivotal manifestation of pediatric SLE and an important prognostic factor. It is hypothesized that activation of the interferon pathway is more pronounced in monogenic forms, in which the response to IFN-I represents the primary alteration and likely the main pathogenic mechanism. This finding may also be relevant in light of the availability of new drugs that selectively target the IFN-I pathway. Demonstration of IFN-I pathway activation could be used as a diagnostic algorithm in aggressive pediatric forms resistant to immunosuppressive therapy and represent a therapeutic target.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
60
* Peripheral blood collection (as part of routine blood draws) on which interferon signature will be performed at the time of enrollment and in case of remission and/or any renal flare. * Renal biopsies (routinely performed for diagnostic purposes and during clinical follow-up) on which Myxovirus resistance protein 1 (MXA) expression and histopathologic characterization will be assessed. * Collection of clinical and laboratory data from routine visits performed at baseline and 3, 6, 12, and 24 months (or last available visit) after the renal biopsy was performed.
Meyer Children's Hospital IRCCS
Florence, Italy
RECRUITINGIRCCS Gianna Gaslini
Genova, Italy
RECRUITINGIRCCS Humanitas Research Hospital
Rozzano, Italy
RECRUITINGDifference between monogenic and non-monogenic forms of cSLE
Quantification of the IFN-I target genes distinguishing between monogenic and non-monogenic forms.
Time frame: At the enrollment, in case of renal flare, in case of disease remission
Evaluation of expression of MXA protein in renal biopsy
Evaluation of expression of MXA protein in renal biopsy (by fluorescence microscopy), distinguishing between genetic and non-genetic forms
Time frame: Biopsy available at enrollment
Evaluation of the proportions of the various WHO histological classes of renal biopsy
Evaluation of the proportions of the various WHO histological classes of renal biopsy in patients with monogenic and non-monogenic lupus nephritis. Histological diagnosis at renal biopsy: WHO histological pattern, activity index, chronicity index, renal TMA
Time frame: At the end of the study (24 months after enrollment)
Phenotype characterization of cSLE
Description of clinical parameters, as SLEDAI-2K, in patients with cSLE and renal involvement, distinguishing between monogenic and non-monogenic forms. Description of laboratory parameters as renal function (eGFR CKiD 25) in patients with cSLE and renal involvement, distinguishing between monogenic and non-monogenic forms
Time frame: At the onset of the disease, 3, 6, 12, 24 months from the kidney biopsy,
Correlation between the clinical phenotype, response to treatment and amplification of the interferon pathway
Correlation between the clinical phenotype (laboratory parameters and during renal flare), response to treatment and amplification of the interferon pathway, distinguishing between monogenic and non-monogenic forms. Clinical, laboratory and histological data relating to any renal flare: number of flares, date of the flare, months from the first biopsy diagnosis of lupus nephritis, clinical manifestations, data from the biopsy performed during the flare, WHO histological pattern compared with the first biopsy, activity index, chronicity index, induction therapy, maintenance therapy
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Time frame: At the onset of the disease, 3, 6, 12, 24 months from the kidney biopsy,