Clinical trial NCT05803356: Genetic and Immunologic Characterization of IEI
Official title: Genetic and Immunologic Characterization of Inborn Errors of Immunity
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Immunity Disorders
Inborn Errors of Immunity
Keywords: inborn errors of immunity
genotype-phenotype correlation
drugs repositioning
genetics
Lead sponsor: IRCCS Burlo Garofolo
Sponsor class: OTHER
First posted: 2023-04-07
Enrollment: 156
Sex: ALL
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Pediatrics subjects with suspected Inborn Errors of Immunity

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.


Eligibility criteria: Inclusion Criteria:

* Subjects with suspected IEI

Exclusion Criteria:

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

Primary outcomes:
measure: To identify immunologic-functional characteristics of IEI subjects
timeFrame: Within 30 days of enrollment
measure: To identify genetic characteristics of IEI subjects
timeFrame: Within 30 days of enrollment
Secondary outcomes:
Other outcomes:
Locations:
city: Trieste
country: Italy
facility: IRCCS materno infantile Burlo Garofolo
Study officials:
affiliation: IRCCS materno infantile Burlo Garofolo
name: Alberto Tommasini, MD
role: STUDY_DIRECTOR
References: