Descriptive Study of Baseline Features and Longitudinal Prognosis of Lymphoproliferative Manifestations in Primary Immunodeficiencies
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 60
- 主要终点
- Occurrence of Major Clinical Events
研究概览
简要总结
Primary immunodeficiencies (PIDs) are a heterogeneous group of inborn errors of immunity characterized not only by increased susceptibility to infections but also by immune dysregulation. Among immune dysregulation manifestations, lymphoproliferative disorders represent a frequent and clinically challenging complication. These manifestations may involve secondary lymphoid organs (lymphadenopathy, splenomegaly) as well as extranodal organs such as lungs, liver, and gastrointestinal tract, often with lymphocytic and/or granulomatous infiltration. In some patients, lymphoproliferation may progress to lymphoma or other malignancies.
Despite increasing knowledge about specific genetic subtypes of PIDs and the development of targeted therapies (e.g., PI3Kδ inhibitors, CTLA4 pathway modulation, mTOR inhibitors), the natural history and long-term prognosis of lymphoproliferative manifestations across unselected PID populations remain poorly defined. Most available studies focus on selected molecular subgroups or treatment responses, while real-world longitudinal data on broader PID cohorts are lacking.
The PID-LP study is a multicenter retrospective longitudinal study conducted in three tertiary care centers in France. It aims to describe the initial characteristics and long-term outcomes of patients with PIDs who develop lymphoproliferative manifestations.
The primary objective is to evaluate the occurrence of major clinical events during follow-up, defined as death (all causes), occurrence of lymphoma or other malignancy, or clinically significant organ dysfunction attributable to lymphoproliferation.
Secondary objectives are to describe the longitudinal evolution of systemic lymphoproliferation (lymph node size, splenomegaly), the progression of organ involvement (pulmonary, hepatic, gastrointestinal), and to identify clinical, biological, genetic, radiological, and therapeutic factors at diagnosis that may predict major complications.
Approximately 60 pediatric and adult patients diagnosed between 2014 and 2025 and followed for at least 12 months after diagnosis of lymphoproliferation will be included. Data will be retrospectively collected from medical records.
This study is expected to improve the understanding of prognosis and disease trajectories in PID-associated lymphoproliferation, inform follow-up strategies, and generate hypotheses for future prospective interventional studies.
详细描述
Primary immunodeficiencies (PIDs), also referred to as inborn errors of immunity, encompass a broad and expanding spectrum of genetically defined disorders affecting immune system development and function. While historically characterized by recurrent or severe infections, it is now well established that immune dysregulation represents a major component of PID-related morbidity. Autoimmunity, autoinflammation, granulomatous disease, and lymphoproliferation are frequently observed and may dominate the clinical phenotype.
Lymphoproliferative manifestations in PIDs include persistent or recurrent lymphadenopathy, splenomegaly, benign lymphoid hyperplasia, granulomatous infiltration, and, in some cases, progression to lymphoma or other malignancies. These manifestations may involve secondary lymphoid organs but also extranodal sites such as the lungs (interstitial lung disease, lymphoid infiltrates), liver (nodular regenerative hyperplasia, fibrosis), gastrointestinal tract (lymphocytic or granulomatous inflammation), and other organs. Organ dysfunction secondary to lymphoproliferation may lead to significant morbidity, including respiratory impairment, portal hypertension, malabsorption, cytopenias, or the need for invasive procedures.
Several recent studies have evaluated targeted therapies in selected molecular subgroups of PIDs associated with immune dysregulation. For example, PI3Kδ inhibitors have demonstrated efficacy in activated PI3Kδ syndrome (APDS), abatacept has shown benefit in CTLA4 or LRBA deficiency, and mTOR inhibitors such as sirolimus have been used in autoimmune lymphoproliferative syndromes and related disorders. However, these studies focus on specific genetic entities and therapeutic responses over relatively short follow-up periods. There remains a lack of comprehensive longitudinal data describing the real-world evolution of lymphoproliferative manifestations across heterogeneous PID populations.
The PID-LP study is a multicenter retrospective longitudinal study conducted in three French tertiary referral centers (Nancy, Strasbourg, and Metz). It is designed to analyze existing clinical data collected during routine care. The study population includes pediatric and adult patients diagnosed with a PID according to the International Union of Immunological Societies (IUIS) classification, who developed systemic lymphoproliferation (lymphadenopathy, splenomegaly, lymphoma) and/or organ involvement attributable to lymphocytic or granulomatous infiltration in the context of PID. Eligible patients must have at least 12 months of follow-up after the first diagnosis of lymphoproliferation.
The primary objective is to evaluate the occurrence of major clinical events during follow-up. The primary endpoint is defined as the occurrence of at least one of the following:
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Retrospective
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of primary immunodeficiency (inborn error of immunity) according to ESID criteria
- •Presence of systemic lymphoproliferative manifestations (e.g., persistent lymphadenopathy, splenomegaly, lymphoma) and/or organ involvement attributable to lymphocytic or granulomatous infiltration
- •Diagnosis of lymphoproliferative manifestation between January 1, 2014 and December 31, 2025
- •Minimum follow-up of 12 months after diagnosis of lymphoproliferative manifestation
- •Followed in one of the participating centers
排除标准
- •Secondary immunodeficiency (e.g., HIV infection, immunosuppression due to chemotherapy, solid organ transplantation, or other acquired causes)
- •Isolated reactive lymphadenopathy clearly attributable to acute infection without evidence of persistent lymphoproliferation
- •Insufficient clinical data available in medical records to assess baseline characteristics or outcomes
- •Follow-up duration < 12 months after diagnosis of lymphoproliferative manifestation
结局指标
主要结局
Occurrence of Major Clinical Events
时间窗: 12 months minimum to 10 years retrospective follow-up from first documented benign lymphoproliferative manifestation
The primary outcome is the occurrence of at least one major clinical event during follow-up, defined as any of the following: * All-cause mortality; * Diagnosis of lymphoma or other malignancy; * Clinically significant organ dysfunction attributable to lymphoproliferative involvement (including pulmonary, hepatic, gastrointestinal, or splenic complications), as documented by clinical, biological, and/or radiological criteria and requiring specific medical or surgical management. Each event will be recorded as a time-to-event variable from the date of lymphoproliferation diagnosis.
次要结局
- Longitudinal Evolution of Systemic Lymphoproliferation(12 months minimum to 10 years retrospective follow-up from first documented benign lymphoproliferative manifestation)
- Longitudinal Evolution of Organ-Specific Involvement(12 months minimum to 10 years retrospective follow-up from first documented benign lymphoproliferative manifestation)
- Occurrence of major clinical events according to baseline patient characteristics(12 months minimum to 10 years retrospective follow-up from first documented benign lymphoproliferative manifestation)