Идёт набор NCT04902807

Conception of a Diagnosis, Prognosis and Therapeutic Decision Tool for Patients With Autoimmunity and Inflammation

— Наблюдательное Autoimmune Lymphoproliferative Syndrome Autoimmune Cytopenia Autoimmune Diseases Autoimmune Anemia

Ориентир для пациента и семьи

Простыми словами

Автоматическая сводка по структурированным данным реестра. Она помогает сориентироваться, но не заменяет официальный протокол или оценку врача.

Что изучают: В протоколе указаны: Collection of samples.
Кому может быть актуально: Состояния в реестре: Autoimmune Lymphoproliferative Syndrome, Autoimmune Cytopenia, Autoimmune Diseases, Autoimmune Anemia. Базовые параметры: 1 год — 18 лет · Все.
Что важно проверить: Возраст, диагноз и пол — только базовые ориентиры. Предыдущее лечение, анализы и другие обязательные условия указаны ниже в критериях участия.
Где проводится: Франция
Следующий шаг: Сохраните исследование, покажите его лечащему врачу и уточните актуальный статус у исследовательского центра. Расходы, документы и поездка →

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Обзор

The main objective of this study is to generate diagnosis and therapeutic-decision tools through the identification of molecular causes of PIDs with autoimmunity/inflammation and the variability in disease outcome at the transcriptional level using a combination of omics signatures (transcriptomics, epigenomics, proteomics, metagenomics, metabolomics and lipidomics).

Подробное описание

Primary Immune deficiencies (PIDs) are a group of monogenic diseases related to developmental or functional dysfunction of one or several immune cell types. Individually there are rare entities, but collectively they group several thousands of patients.

Approximately 500 000 patients suffer from PIDs worldwide, making their management a true health-care concern. According to European Society for Immunodeficiencies (ESID), the age group in which PIDs is most frequently diagnosed is under 19 years of age (62%)1. PIDs are causing susceptibility to severe and life-threatening infections by common pathogens, but they also predispose to cancer and can initially manifest as autoimmune and inflammatory diseases.

Multiple mechanisms underlie the development of autoimmunity/inflammation in PIDs. Moreover, their development can be influenced by the composition of the microbiota, which shapes host metabolic and immune functions and can be modified by many environmental factors. In the last two decades a particular emphasis was given to the elucidation of the genomic mutations causing PIDs. This led to a burst of genetic diagnosis as the numbers of known monogenic causes of PIDs rose from around 200 in 2010 to more than 310 in 2017. These genomic approaches revealed that: 1) a given monogenic defect can lead to very dissimilar clinical presentations, disproving the initial concept that a monogenic defect is associated with specific clinical manifestations ; and 2) the number of cases of autosomal dominant genetic deficiencies has increased, with sometimes a partial clinical penetrance so that some relatives carrying the causal genetic variant remain asymptomatic. Hence, onset and presentation of autoimmune and inflammatory diseases in PIDs is highly unpredictable.

PIDs with autoimmunity/inflammation usually require life-long symptomatic treatments including broad immunosuppression or immunotherapies. On the long term, such treatments can have important side effects or poor efficacy and they result in high burden cost. It is therefore crucial to diagnose PIDs as early as possible in order to select the most efficient therapy based not only on clinical features as it is nowadays, but to include the underlying molecular cause of immune dysregulation.

The central goal of this project is to explain the very variable outcome of monogenic autoimmune and inflammatory diseases and to define predictive biomarkers in order to stratify patients and to optimize therapeutic choices.

Вмешательства

Биопрепарат Collection of samples
Blood, Urine and Stool samples will be collected from the participants.

Первичные конечные точки

Generate a diagnosis and therapeutic-decision tools [Срок оценки: 5 years]

Вторичные конечные точки (3)

1- Development of an atlas of molecular interactions leading to autoimmunity and inflammation [Срок оценки: 5 years]
2 - To develop an artificial intelligent online application [Срок оценки: 5 years]
3- Ancillary study (pilot study) [Срок оценки: 5 years]

Критерии участия

Inclusion Criteria for controls (patients relatives and unrelated subjects):

Individuals aged<18 y/o.
Individuals > 6 kg
Individuals not affected by an immune-related disease or not affected by cancer
Individuals whose parents have signed an enlightened consent.

Inclusion criteria for patients

Individuals with health insurance.
Patients treated at Necker hospital with PIDs and autoimmunity/inflammation related to known genetic defects (cytopenia, Enteropathy Inflammatory bowel disease (IBD), Systemic Lupus Erythematosus (SLE), Juvenile Idiopathic Arthritis (JIA), Familial Hemophagocytic Lymphohistiocytosis (FHL), chronic EBV infection associated (Ca-EBV) with EBV-infected T and/or Natural Killer (NK) cells and with a high risk to develop macrophage activation syndrome similar to FHL. See table below for diagnosis inclusion criteria.
Individuals aged<18 y/o.
Individuals > 9 kg
Patients whose parents have signed an enlightened consent.