Immunodysregulation As an Expression of Underlying Inborn Errors of Immunity: Implementation of Diagnostics and Management of Pediatric and Adult Patients with Immune System Disorders

Recruiting

• Conditions: Inborn Errors of Immunity

• Registration Number: NCT06773546
• Lead Sponsor: IRCCS Azienda Ospedaliero-Universitaria di Bologna

Brief Summary

This is an observational, retro-prospective, moncentric study focused on Inborn Errors of Immunity, an heterogeneous group of inherited diseases due to defects in the differentiation and/or function of the immune system. The primary aim of this study is to obtain a clinical-immunological, functional and molecular characterisation of paediatric and adult patients with confirmed or suspected Inborn Errors of Immunity, particularly of patients with manifestations of immunedysregulation, focusing on clinical course, immunophenotypic laboratory and functional abnormalities, genetic background.

Detailed Description

Due to the observational nature of the study, patients were and will be treated according to normal clinical practice and in accordance with medical judgement. The following evaluations were performed in the retrospective cohort and will be performed in the prospective cohort:

* Standard haematochemical examinations;

* Extended lymphocyte typing;

* Plasma dosage of immunoglobulins;

* Evaluation of early and late responses to Measles-Parotitis-Rosolia and Diphtheria-Tetanus-Pertussis vaccinations;

* Evaluation of antibody responses to vaccines against Haemophilus Influenzae, Neisseria Meningitidis and Pneumococcus;

* Detection of auto-antibodies on HEp-2 cells, and of auto-antibodies directed against haemopoietic cells and proteins of innate and adaptive immunity;

* Plasma dosage of complement factors (C3, C4);

* Radiological assessment;

* Functional immunological assay;

* Molecular-genetic investigations of targeted gene panels involved in immunodysregulation and Inborn Errors of Immunity.

Study Timeline

• Study Start: 2023-09-15
• Status Verified: 2024-10
• Study First Submitted: 2024-12-03
• Study First Submitted QC: 2025-01-13
• Last Update Submitted: 2025-01-13
• Study First Posted: 2025-01-14
• Last Update Posted: 2025-01-14
• Primary Completion: 2026-06-30
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 400

Inclusion Criteria

• patients with confirmed or suspected Inborn Errors of Immunity;
• age < 50 years at onset of clinical features suspected for Inborn Errors of Immunity;
• obtaining informed consent from patients or parents/legal guardian of pediatric patients.

Exclusion Criteria

• patients in whom infectious susceptibility and immunodysregulation can only be attributed to known non-immunological causes: acquired immunodeficiency secondary to chronic infections (HIV), and acquired immunodeficiency secondary to immunosuppressive treatment.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Mortality	1 year after diagnosis of Inborn Errors of Immunity	time-to-event from diagnosis of Inborn Errors of Immunity up to 1 year
Category of diagnsoed Inborn Error of Immunity	at baseline	categories I to X
Qualitative or quantitative alterations in innate immunity and/or adaptive immunity	at baseline	presence or absence of alterations
Infective susceptibility	at baseline and every 6 months up to 1 year	presence of one of the following conditions: invasive, severe, persistent, recurrent, opportunistic and/or vaccine strain infections
Immunodisregulation	at baseline and every 6 months up to 1 year	presence of at least one disorder among atopy, hyperinflammation, autoimmunity, non-clonal lymphoproliferation and/or malignant neoplasms

Trial Locations

Locations (1)

IRCCS Azienda Ospedaliero-Universitaria di Bologna; 🇮🇹 Bologna, Bolgona, Italy