Abstract

PRECISION THERAPEUTICS IN PRIMARY IMMUNE REGULATORY DISORDERS: CURRENT ADVANCES AND FUTURE DIRECTIONS

Neeraja Sunil*, Nissy Mariam Reji, Melvin Sam Mathew, Abhilash Kumar B.

ABSTRACT

Primary immune regulatory disorders (PIRDs) are a heterogeneous group of inborn errors of immunity characterized by impairment of immune tolerance and homeostasis leading to autoimmune, autoinflammatory, lymphoproliferative diseases and recurrent infections. Recent developments in molecular genetics and next-generation sequencing have enhanced knowledge on the genetic and immunologic basis of these diseases leading to improved diagnosis and more accurate disease classification. Standard immunosuppressive treatments are still essential for disease management; nevertheless, the advances made in precision medicine have changed the way of managing PIRDs with the help of targeted therapy aimed at specific pathways. Agents such as abatacept, sirolimus, JAK inhibitors and PI3Kδ inhibitors have shown promise in selected disorders, whereas HSCT may be a potential curative approach for more severe diseases. Moreover, gene therapy and genome editing approaches can contribute to future improvements in correction of genetic disorders and development of individualized treatments. However, many issues such as late diagnosis, limited availability of genetic testing, high treatment costs and lack of long-term outcomes of treatments have an impact on patient care. This review highlights the current knowledge about immunopathogenesis, clinical presentation, diagnostic criteria and precision therapies for PIRDs, as well as recent developments, current challenges and future directions in this field.

Keywords: Primary immune regulatory disorders, Inborn errors of immunity, Precision medicine, Targeted therapy, Hematopoietic stem cell transplantation, Gene therapy, Immune dysregulation.