The recognition of immune dysregulation as a pathogenetic mechanism of new Inborn Errors of Immunity (IEIs) led to an extension of the paradigm of immunodeficiency. Indeed, the clinical phenotype of IEI ranges from increased susceptibility to infections to autoimmunity, allergy, autoinflammation, lymphoproliferation and malignancy. Therefore, new awareness of additional warning signs to suspect IEIs led to an expansion of the disciplines involved in the diagnostic process, making it extremely complex. Moreover, the rapid evolution of the molecular diagnosis of IEIs through high-throughput next-generation sequencing technologies has also expanded the possibility of introducing targeted therapies which specifically address the underlying genetic defects.

Historically, the management of IEIs was limited to antimicrobial treatment and prophylaxis, immunoglobulin replacement, immunosuppressive agents “borrowed” from other indications, and bone marrow transplantation in specific diseases. In most recent years, the recognition of immune dysregulation as pathogenetic mechanism of a subcategory of IEIs, together with the advancing of molecular diagnosis, has set the basis for the development of targeted therapies able to modulate the underlaying dysregulated pathway.
New drugs have been developed, including checkpoint inhibitors, targeted immunosuppressants, and monoclonal antibodies. These targeted approaches have shown efficacy in reversing clinical manifestations, preventing end-organ damage, and in decreasing pretransplant disease burden, when used as bridge strategies. However, as IEIs are rare diseases, they are inherently difficult to study in controlled clinical trials. Moreover, long-term data are needed to understand the full efficacy, the dose-findings, the length of treatment, the side effects (on and off target), and the ability to restore the impaired immune function of these molecules. Beyond this, recent advances in hematopoietic stem cell transplantation, gene therapy and gene editing approaches also provide new therapeutic options for IEIs.

Immune dysregulation as underlying pathogenetic mechanism of IEIs has proven to be a therapeutic challenge. The present Research Topic aims to collect scientific studies about the multiple aspects of the therapeutic approaches of IEIs based on their causative molecular defects, helping to contribute to define optimal clinical management of IEIs in the evolution of precision medicine.

This Research Topic accepts:
Original Research, Systematic Review, Methods, Review and Mini-Review, Policy and Practice Reviews, Hypothesis & Theory, Clinical Trial, Classification, Technology and Code, Study Protocol, Perspective, Case Report, Brief Research Report, Data Report, General Commentary, and Opinion. We welcome manuscripts focusing on, but not limited to, the following sub-topics:

• Immunomodulation/immunosuppressive agents for the treatment of immune dysregulation

• Use of targeted treatments for immune dysregulation

• HSCT and gene therapy in patients with immune dysregulation

• Research perspective in the field of immune dysregulation

Topic editor Giorgia Bucciol received financial support from CSL Behring (speaker's fees paid to institution).
All other Topic Editors declare no competing interests with regards to the Research Topic subject.

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Treating Immune Dysregulation in Inborn Errors of Immunity: from conventional strategies to targeted therapies