Research Topic

Novel Therapeutic Approaches to Primary Immunodeficiencies

About this Research Topic

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?


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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?


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

About Frontiers Research Topics

With their unique mixes of varied contributions from Original Research to Review Articles, Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author.

Topic Editors

Loading..

Submission Deadlines

21 September 2020 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

Loading..

Topic Editors

Loading..

Submission Deadlines

21 September 2020 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

Loading..
Loading..

total views article views article downloads topic views

}
 
Top countries
Top referring sites
Loading..