Genetic and Immunologic Characterization of IEI

NCT05803356 | Completed

• 1 other identifier: RC 24/17
• Study Type: observational
• Target: 156
• Locations: 1 country
• Sites: 1

Brief Summary

Inborn Errors of Immunity (IEI) include clinically heterogeneous rare genetic diseases depending on mutations in about 300 different genes. Clinically, this group of diseases is characterized by the presence of infectious, inflammatory, autoimmune, and lymphoproliferative symptoms. Understanding the pathogenesis of these diseases can guide the implementation of targeted therapies and improve prognosis. In recent years, IEI have been described that do not necessarily present with repeated infectious symptoms but rather with autoimmune, lymphoproliferative, and autoinflammatory manifestations, or with forms of immunodeficiency with a spectrum of susceptibility to one or few infectious agents. In this case, simple laboratory tests are not sufficient to characterize the disease since no particular immunophenotypic changes are evident. To correct classify the patients and to improve knowledge on the pathogenesis of the diseases, complex immunologic-functional studies are required. These studies should be started prior to genetic analysis, with the aim of targeting and narrowing it down. Although the ever-decreasing costs of Next Generation Sequencing (NGS) methods make it convenient to analyse many genes or even the entire exome simultaneously, the analysis of the data resulting from NGS can be complex and provide results of uncertain interpretation. In these cases, immunologic-functional studies can clarify the real causal role of the identified genetic variants. The identification of genotype-phenotype correlation is crucial to establish new therapeutic targets for diseases orphan of specific etiological treatments. In vitro and in vivo disease models are key tools to test drugs repositioning, as was the case for Lapaquistat in the treatment of periodic fevers caused by de-regulation of the cholesterol metabolic pathway.

Conditions

Immunity Disorders; Inborn Errors of Immunity

Keywords

inborn errors of immunity; genotype-phenotype correlation; drugs repositioning; genetics

Outcome Measures

Primary Outcomes (2)

• To identify immunologic-functional characteristics of IEI subjects

  Several test will be carried out on peripheral blood samples (i.e.,evaluation of lymphocyte subpopulations, natural killer cell degranulation assay, intracellular protein expression analysis, interferon signature in real time PCR).

  Within 30 days of enrollment

• To identify genetic characteristics of IEI subjects

  Using NGS and exome analysis

  Within 30 days of enrollment

Eligibility Criteria

• Age: Up to 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Pediatrics subjects with suspected Inborn Errors of Immunity

You may qualify if:

• Subjects with suspected IEI

You may not qualify if:

• No consent from the patients' guardians
• Subjects undergoing hematopoietic stem cell transplantation.

Sponsors & Collaborators

• IRCCS Burlo Garofolo: lead

Study Sites (1)

IRCCS materno infantile Burlo Garofolo

Trieste, 34137, Italy

Location

Biospecimen

Retention: SAMPLES WITH DNA

Blood samples

MeSH Terms

Conditions

Immune System Diseases

Study Officials

• Alberto Tommasini, MD

  IRCCS materno infantile Burlo Garofolo

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 24, 2023
• First Posted: April 7, 2023
• Study Start: December 20, 2018
• Primary Completion: December 31, 2022
• Study Completion: December 31, 2022
• Last Updated: April 7, 2023

Record last verified: 2023-03

Locations

IT (1)