NCT05803356

Genetic and Immunologic Characterization of IEI

Genetic and Immunologic Characterization of Inborn Errors of Immunity

• Status: Completed
• Phase: —
• Study type: Observational
• Enrollment: 156 (actual)
• Sponsor: IRCCS Burlo Garofolo · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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

Timeline

• Start date: 2018-12-20
• Primary completion: 2022-12-31
• Completion: 2022-12-31
• First posted: 2023-04-07
• Last updated: 2023-04-07

Locations

1 site across 1 country: Italy