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NCT Number: NCT06586710

Interferon Pathway Activation in Monogenic and Nonmonogenic Forms of Pediatric SLE

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.

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Key information

Conditions

Systemic Lupus Erythematosus of Childhood

Age range

1 month–17 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Meyer Children's Hospital IRCCS, Florence, Italy

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Assessment activation of interferon pathway

Other
  • 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.

Primary outcomes

  1. Difference between monogenic and non-monogenic forms of cSLE

    Time frame: At the enrollment, in case of renal flare, in case of disease remission

    Quantification of the IFN-I target genes distinguishing between monogenic and non-monogenic forms.

  2. Evaluation of expression of MXA protein in renal biopsy

    Time frame: Biopsy available at enrollment

    Evaluation of expression of MXA protein in renal biopsy (by fluorescence microscopy), distinguishing between genetic and non-genetic forms

  3. 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)

    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

Secondary outcomes

  1. Phenotype characterization of cSLE

    Time frame: At the onset of the disease, 3, 6, 12, 24 months from the kidney biopsy,

    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

  2. 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,

    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

Study contacts

Contact information is provided by the study sponsor or research team.

Carmela Errichiello, MD

CONTACT

[email protected]

055/5662563

Carmela Errichiello, MD

CONTACT

055/5662563

Sponsors and collaborators

Lead sponsor

Meyer Children's Hospital IRCCS

Other

Registry information

Official study title

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

Important dates

Study start
2023
Primary completion
2025
Study completion
2025
First posted
Sep 19, 2024
Registry last updated
Sep 19, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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