Model Early Immunologic Stages of Pediatric Hematological Pre-lupus (PRELUDE)
Model Early Immunologic Stages of Pediatric Hematological Pre-lupus in Order to Prevent SLE in Children.
Visão geral do estudo
Status
Descrição detalhada
The development of an autoimmune disease (AID) requires several years. In systemic lupus erythematosus (SLE), anti-nuclear antibodies (ANA) appear several years before the onset of the disease. However, it is difficult to identify the early mechanisms of autoimmunity in humans as most patients' samples are obtained at the time of diagnosis.
We hypothesize that immune thrombocytopenic purpura (ITP) in children provides a unique model for understanding the initial mechanisms leading to autoimmunity. Children with ITP have common immune system dysfunctions leading to the production of anti-platelet antibodies. However, despite this supposedly common dysfunction, the course and degree of loss of tolerance of the immune system are very heterogeneous: the disease is transient in 75 to 80% of cases, and 15 to 20% of children with ITP have ANA and their course is usually persistent or chronic. This subgroup of children with hematological AID, ITP ANA+ meets the criteria for a broader form of AID: pre-lupus. We have recently shown that 16% of these children with pre-lupus / ITP-ANA+ progressed to complete SLE within a median of 3.8 years. Why do some children have transient or persistent ITP? limited or systemic ITP? We aim to describe the shared and/or unique immunological pathways involved at diagnosis in children with ITP ANA- (transient or persistent), with ITP ANA+ (pre-lupus condition, transient or persistent), and in patients with SLE (persistent by definition) In this exploratory, prospective, bi-centric cohort study, we will include 70 children with ITP and 20 children with SLE newly diagnosed, over 36 months with a 3-month follow-up for children with ITP-ANA- and SLE and a 48-month follow-up for children with ITP-ANA+. ANA positivity will be defined by a titer ≥ 1/160. Blood samples will be collected at inclusion and at 3 months (bio-collection), and further each 6 months for children with ITP-ANA+. ITP status will be defined at 3 months: transient or persistent. We will analyze the signaling pathways (B and T lymphocytes, cytokines, disruption of tolerance and inactivation of X) involved in these different pathophysiological distinct subgroups
Tipo de estudo
Inscrição (Estimado)
Estágio
- Não aplicável
Contactos e Locais
Contato de estudo
- Nome: Nathalie ALADJIDI, MD
- E-mail: nathalie.aladjidi@chu-bordeaux.fr
Estude backup de contato
- Nome: Jérôme GRANEL, MD
- Número de telefone: +33 5 57 82 02 55
- E-mail: jerome.granel@chu-bordeaux.fr
Locais de estudo
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Bordeaux, França, 33076
- Chu de Bordeaux- Groupe Hospitalier Pellegrin - Hôpital des Enfants
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Contato:
- Jérôme GRANEL, MD
- Número de telefone: +33 5 57 82 02 55
- E-mail: jerome.granel@chu-bordeaux.fr
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Toulouse, França, 31026
- CHU Toulouse - Hôpital des Enfants
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Contato:
- Marlène PASQUET, PROF
- Número de telefone: +33 5 34 55 86 43
- E-mail: pasquet.m@chu-toulouse.fr
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Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
- Filho
- Adulto
Aceita Voluntários Saudáveis
Descrição
Inclusion criteria:
For patients :
- Child or adolescent with newly diagnosed ITP or SLE according to the specific definitions of ITP or SLE, prior to any treatment,
- Over 1 and under 18 years of age at diagnosis, weighing more than 7 kg.
- Written consent from parents or guardians,
- Patient affiliated to a social security scheme.
For controls :
- Over 1 and under 18 years of age at diagnosis, weighing more than 7 kg.
- Follow-up in the day hospital at the Bordeaux University Hospital, for a condition that does not affect the immune system
- Matched on age,
- Written consent from parents or guardians,
- Patient affiliated to a social security scheme
Exclusion criteria:
For patients :
- ITP secondary to a known cause: previous or concomitant immune deficiency, bone marrow or organ transplantation, other autoimmune disease, Evans syndrome (autoimmune hemolytic anemia or autoimmune neutropenia present at ITP diagnosis) or cancer with immunosuppressive therapy.
- Treatment with immunomodulation or immunosuppressants (including immunoglobulins, corticoids, hydroxychloroquine), started prior to inclusion (day of sampling).
- Pregnant women, women in labour and breastfeeding women
For controls :
- Suffering from an immunological disease,
- Infection within fifteen days prior to inclusion,
- Immunomodulatory therapy.
- Pregnant women, women in labour and breastfeeding women
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Outro
- Alocação: Não randomizado
- Modelo Intervencional: Atribuição Paralela
- Mascaramento: Nenhum (rótulo aberto)
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
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Outro: Controles
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Blood sampling is a routine biological procedure performed under the same conditions as during a follow-up consultation.
Monitoring for Systemic Lupus Erythematosus according to SLICC 2012 classification criteria
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Outro: ITP-ANA-
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Blood sampling is a routine biological procedure performed under the same conditions as during a follow-up consultation.
Monitoring for Systemic Lupus Erythematosus according to SLICC 2012 classification criteria
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Outro: ITP-ANA+
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Blood sampling is a routine biological procedure performed under the same conditions as during a follow-up consultation.
Monitoring for Systemic Lupus Erythematosus according to SLICC 2012 classification criteria
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Outro: SLE
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Blood sampling is a routine biological procedure performed under the same conditions as during a follow-up consultation.
Monitoring for Systemic Lupus Erythematosus according to SLICC 2012 classification criteria
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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
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Characterisation of B and T lymphocyte populations
Prazo: Baseline, Month 3 visit.
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Characterisation of B and T lymphocyte populations through the study of surface markers and intracellular factors.
This panel will, in particular, enable the identification of effector B cells such as plasma blasts, subsets of auto-reactive 'double-negative' (DN) B cells, regulatory B cells, and follicular T helper (Tfh) and peripheral extra-follicular T helper (Tph) cells.
Each population will be compared between the patients and the control group.
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Baseline, Month 3 visit.
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Plasma markers
Prazo: Baseline, Month 3 visit.
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Soluble cytokines and factors regulating B-cell survival (BAFF, TACI, IL-6, IL-12p70, IFN-γ, IFN-β, TGF-β, and the IFN-regulated chemokine CXCL10) will be quantified in plasma using a customised multiplex Luminex assay.
Interferon alpha levels will be specifically measured using ultra-sensitive SIMOA (Single Molecule Array) technology.
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Baseline, Month 3 visit.
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Plasma markers
Prazo: Baseline, Month 3 visit.
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Circulating plasma autoantigens - soluble P-selectin and CD40L derived from platelet activation - will be measured by ELISA.
The levels of circulating and mitochondrial DNA will be measured by quantitative RT-PCR in collaboration with V. Sisirak (DR CNRS, Immunoconcept).
The overall activity of plasma DNases will be determined by an in vitro DNA degradation assay.
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Baseline, Month 3 visit.
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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
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Single-cell transcriptomic analysis
Prazo: Baseline, Month 3 visit , Month 6 visit , Month 12 visit, Month 18 visit, Month 24 visit , Month 30 visit, Month 36 visit, Month 42 visit and Month 48 visit.
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Using single-cell RNA sequencing, a single-cell transcriptomic analysis, we will be able to quantify and analyse the transcriptomes of lymphocytes B This will enable us to characterise heterogeneous cell populations, as well as to reconstruct cell development pathways and model transcriptomic dynamics. This technique will enable the modelling of signalling pathways involving B lymphocytes in the subgroup of ITP patients with positive AAN titres, and the development of an algorithm and a mathematical model of the progression of these cellular and molecular markers |
Baseline, Month 3 visit , Month 6 visit , Month 12 visit, Month 18 visit, Month 24 visit , Month 30 visit, Month 36 visit, Month 42 visit and Month 48 visit.
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Single cell epigenetic analysis
Prazo: Baseline, Month 3 visit , Month 6 visit , Month 12 visit, Month 18 visit, Month 24 visit , Month 30 visit, Month 36 visit, Month 42 visit and Month 48 visit.
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Using single-cell ATAC sequencing, we will be able to analyse the regions of DNA accessible to the transcription machinery. This will enable us to identify regulatory programmes such as signalling pathways. The analysis will also reveal heterogeneity amongst B-cell subpopulations, which may respond differently to signals. This will provide insight into the epigenetic status of genes, or at least into which factors regulate this signalling pathway and how the cell adjusts its response depending on its situation or stage of maturity, or on the signal itself. |
Baseline, Month 3 visit , Month 6 visit , Month 12 visit, Month 18 visit, Month 24 visit , Month 30 visit, Month 36 visit, Month 42 visit and Month 48 visit.
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Colaboradores e Investigadores
Patrocinador
Investigadores
- Investigador principal: Jérôme GRANEL, MD, University Hospital, Bordeaux
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo (Estimado)
Conclusão Primária (Estimado)
Conclusão do estudo (Estimado)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Real)
Atualizações de registro de estudo
Última Atualização Postada (Real)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
- Citopenia
- Processos Patológicos
- Doenças do Tecido Conjuntivo
- Doenças autoimunes
- Doenças do sistema imunológico
- Hemorragia
- Manifestações de pele
- Doenças Hematológicas
- Distúrbios da Coagulação Sanguínea
- Distúrbios hemorrágicos
- Distúrbios das plaquetas sanguíneas
- Microangiopatias Trombóticas
- Púrpura Trombocitopênica
- Púrpura
- Trombocitopenia
- Condições Patológicas, Sinais e Sintomas
- Doenças da Pele e do Tecido Conjuntivo
- Sinais e sintomas
- Doenças hemic e linfáticas
- Lúpus Eritematoso Sistêmico
- Púrpura Trombocitopênica Idiopática
Outros números de identificação do estudo
- CHUBX 2025/052
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