Clinical trial NCT06586710: 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.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Systemic Lupus Erythematosus of Childhood
Lead sponsor: Meyer Children's Hospital IRCCS
Sponsor class: OTHER
First posted: 2024-09-19
Enrollment: 60
Sex: ALL
Minimum age (years): 1
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: 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.

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.

Primary outcomes:
measure: Difference between monogenic and non-monogenic forms of cSLE
timeFrame: At the enrollment, in case of renal flare, in case of disease remission
measure: Evaluation of expression of MXA protein in renal biopsy
timeFrame: Biopsy available at enrollment
measure: Evaluation of the proportions of the various WHO histological classes of renal biopsy
timeFrame: At the end of the study (24 months after enrollment)
Secondary outcomes:
measure: Phenotype characterization of cSLE
timeFrame: At the onset of the disease, 3, 6, 12, 24 months from the kidney biopsy,
measure: Correlation between the clinical phenotype, response to treatment and amplification of the interferon pathway
timeFrame: At the onset of the disease, 3, 6, 12, 24 months from the kidney biopsy,
Other outcomes:
Locations:
city: Firenze
country: Italy
facility: Meyer Children's Hospital IRCCS
city: Genova
country: Italy
facility: IRCCS Gianna Gaslini
city: Rozzano
country: Italy
facility: IRCCS Humanitas Research Hospital
Study officials:
affiliation: Meyer Children's Hospital IRCCS, Florence, Italy
name: Carmela Errichiello
role: PRINCIPAL_INVESTIGATOR
References: