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

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.

Study Overview

• Status: Recruiting
• Conditions: Inborn Errors of Immunity

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 Type: Observational
• Enrollment (Estimated): 400

Contacts and Locations

• Study Contact: Name: Francesca Conti; Phone Number: 00390512144666; Email: francesca.conti27@unibo.it

Study Locations

• Italy
  • Bolgona
    • Bologna, Bolgona, Italy, 40138
      • Recruiting
      • IRCCS Azienda Ospedaliero-Universitaria di Bologna
      • Contact: Francesca Conti; Phone Number: 00390512144666; Email: francesca.conti27@unibo.it
      • Contact: Francesca Conti

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with confirmed or suspected Inborn Errors of Immunity, in particular patients with an immunodysregulated condition (autoimmunity, allergy, hyperinflammation and non-clonal lymphoproliferation, susceptibility to the development of malignant neoplasms) aged < 50 years at onset of clinical features suspected for Inborn Errors of Immunity, who referred to the Pediatrics Unit of the IRCCS Azienda Ospedaliero-Universitaria di Bologna Policlinico di Sant'Orsola, Italy.

Description

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 Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: IRCCS Azienda Ospedaliero-Universitaria di Bologna
• Investigators: Principal Investigator: Francesca Conti, MD, IRCCS Azienda Ospedaliero-Universitaria di Bologna

Study record dates

Study Major Dates

• Study Start (Actual): September 15, 2023
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: December 3, 2024
• First Submitted That Met QC Criteria: January 13, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 13, 2025
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Inborn errors of immunity
• Additional Relevant MeSH Terms: Immune System Diseases
• Other Study ID Numbers: ID-TYPE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No