Interferon Pathway Activation in Monogenic and Nonmonogenic Forms of Pediatric SLE

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Другое 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

Первичные конечные точки

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

Вторичные конечные точки (2)

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

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Фундаментальное исследование

Центры проведения

Италия · 3 центра

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

Идентификаторы

NCT: NCT06586710 · NEFRO-LES

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗