Interferon Pathway Activation in Monogenic and Nonmonogenic Forms of Pediatric SLE

Official title

Interferon Pathway Activation in Monogenic and Non-monogenic Forms of Pediatric SLE With Renal Involvement. Multicenter Observational Study of Biological Samples.

Overview

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.

Detailed description

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.

Interventions

• Other Assessment activation of interferon pathway
  * 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 m

Primary outcome measures

• Difference between monogenic and non-monogenic forms of cSLE [Time frame: At the enrollment, in case of renal flare, in case of disease remission]
• Evaluation of expression of MXA protein in renal biopsy [Time frame: Biopsy available at enrollment]
• Evaluation of the proportions of the various WHO histological classes of renal biopsy [Time frame: At the end of the study (24 months after enrollment)]

Secondary outcome measures (2)

• Phenotype characterization of cSLE [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 [Time frame: At the onset of the disease, 3, 6, 12, 24 months from the kidney biopsy,]

Eligibility criteria

Inclusion criteria

• Diagnosis of SLE arising before the age of majority (until the age of 18 years) according to SLICC and/or EULAR criteria 2019;
• Clinical, laboratory and/or histologic evidence of renal involvement manifested before the age of 18 years;
• Signature of informed consent.

Exclusion criteria

• Onset of renal disease after the age of 18 years;
• SLE secondary to drugs or associated with other diseases such as systemic sclerosis, rheumatoid arthritis, Sjögren's syndrome, and other connectivities.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Basic science

Study locations

Italy · 3 centers

• Meyer Children's Hospital IRCCS — Florence
• IRCCS Gianna Gaslini — Genova
• IRCCS Humanitas Research Hospital — Rozzano

Identifiers

NCT: NCT06586710 · NEFRO-LES

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗