Primary immunodeficiency disorders (PIDs) are rare inherited monogenic disorders of the immune system, characterized by an increased risk of infection, immune dysregulation and malignancies. More than 400 PIDs have been identified to date. Given the high number of genetic defects and the significant overlap among different disorders, the identification of the genetic basis of the diseases starting from clinical and/or immunological findings may be difficult, leading to a delay between the onset of symptoms and the diagnosis. In the last few years, the identification of PID patients became easier, thanks to the introduction of high throughput sequencing (HTS) technologies and newborn screening. The simultaneous sequencing of a panel of genes through HTS, indeed, allowed clinicians to rapidly identify affected genes. As a consequence, since HTS was introduced, the number of identified gene defects responsible of PIDs has been markedly increasing, and several novel clinical phenotypes have been associated to already known gene defects.
The improvement of the process of gene discovery in PIDs has led to the identification of novel pathogenic mechanisms and candidate targets to develop precision treatments. Targeted therapies are particularly effective for the treatment of hyperimmune conditions and may be successful in previously incurable conditions. Moreover, the use of targeted therapies may reduce the incidence of side effects compared to conventional treatments. For example, the use of small molecule inhibitors, such as Leniolisib and Ruxolitinib, or the use of immunomodulators, such as Abatacept, have been proven to be effective in reducing the recurrence of infections, in preventing lymphoma development and in treating refractory autoimmune manifestations in patients with Activated PI3K delta syndrome (APDS), STAT1 gain of function mutations and CTLA-4/LRBA deficiency, respectively. Moreover, these targeted treatments may help in reducing the use of steroids and potent immunosuppressive drugs in patients with PIDs with immune-dysregulation, in turn reducing the incidence of adverse drug events. Similarly, using gene therapy in different PIDs prevents the procedure related mortality and the risk of graft versus host disease and solves the problem of donor availability.
This Research Topic is focused to provide a comprehensive overview of the latest research on novel therapeutic approaches to primary immunodeficiencies. We seek Original Research, Reviews, Mini-Reviews, Methods, and Perspective articles addressing, although not limited to, the following topics:
1. Treating primary immunodeficiencies in the era of precision medicine
2. Gene editing and gene therapy in PIDs
3. Small molecules in PIDs
4. Novel therapeutic approaches to Familial HLH and its neurological manifestations
5. Regenerative medicine in PIDs: where are we?
Primary immunodeficiency disorders (PIDs) are rare inherited monogenic disorders of the immune system, characterized by an increased risk of infection, immune dysregulation and malignancies. More than 400 PIDs have been identified to date. Given the high number of genetic defects and the significant overlap among different disorders, the identification of the genetic basis of the diseases starting from clinical and/or immunological findings may be difficult, leading to a delay between the onset of symptoms and the diagnosis. In the last few years, the identification of PID patients became easier, thanks to the introduction of high throughput sequencing (HTS) technologies and newborn screening. The simultaneous sequencing of a panel of genes through HTS, indeed, allowed clinicians to rapidly identify affected genes. As a consequence, since HTS was introduced, the number of identified gene defects responsible of PIDs has been markedly increasing, and several novel clinical phenotypes have been associated to already known gene defects.
The improvement of the process of gene discovery in PIDs has led to the identification of novel pathogenic mechanisms and candidate targets to develop precision treatments. Targeted therapies are particularly effective for the treatment of hyperimmune conditions and may be successful in previously incurable conditions. Moreover, the use of targeted therapies may reduce the incidence of side effects compared to conventional treatments. For example, the use of small molecule inhibitors, such as Leniolisib and Ruxolitinib, or the use of immunomodulators, such as Abatacept, have been proven to be effective in reducing the recurrence of infections, in preventing lymphoma development and in treating refractory autoimmune manifestations in patients with Activated PI3K delta syndrome (APDS), STAT1 gain of function mutations and CTLA-4/LRBA deficiency, respectively. Moreover, these targeted treatments may help in reducing the use of steroids and potent immunosuppressive drugs in patients with PIDs with immune-dysregulation, in turn reducing the incidence of adverse drug events. Similarly, using gene therapy in different PIDs prevents the procedure related mortality and the risk of graft versus host disease and solves the problem of donor availability.
This Research Topic is focused to provide a comprehensive overview of the latest research on novel therapeutic approaches to primary immunodeficiencies. We seek Original Research, Reviews, Mini-Reviews, Methods, and Perspective articles addressing, although not limited to, the following topics:
1. Treating primary immunodeficiencies in the era of precision medicine
2. Gene editing and gene therapy in PIDs
3. Small molecules in PIDs
4. Novel therapeutic approaches to Familial HLH and its neurological manifestations
5. Regenerative medicine in PIDs: where are we?