Precision medicine: The use of tailored therapy in primary immunodeficiencies

Abstract

Primary immunodeficiencies (PID) are rare, complex diseases that can be characterised by a spectrum of phenotypes, from increased susceptibility to infections to autoimmunity, allergy, auto-inflammatory diseases and predisposition to malignancy. With the introduction of genetic testing in these patients and wider use of next-Generation sequencing techniques, a higher number of pathogenic genetic variants and conditions have been identified, allowing the development of new, targeted treatments in PID. The concept of precision medicine, that aims to tailor the medical interventions to each patient, allows to perform more precise diagnosis and more importantly the use of treatments directed to a specific defect, with the objective to cure or achieve long-term remission, minimising the number and type of side effects. This approach takes particular importance in PID, considering the nature of causative defects, disease severity, short- and long-term complications of disease but also of the available treatments, with impact in life-expectancy and quality of life. In this review we revisit how this approach can or is already being implemented in PID and provide a summary of the most relevant treatments applied to specific diseases.

Primary immunodeficiency disease in children: A significant but rare cause of failure to thrive

“…Early initiation of supportive treatment includes antibiotics or antifungal, balanced nutrition, vaccination, and immunoglobulin replacement therapy are crucial to prevent further deterioration [9,10]. Definitive therapy includes such as haematopoietic stem cells transplantation and bone marrow transplant are the treatment option that life rescuer for patient with severe types of PID for example severe combined immunodeficiency (SCID) [9]. Further hope on gene therapy is still debatable and under research.…”

Treg in inborn errors of immunity: gaps, knowns and future perspectives

“…Moreover, a recent clinical trial explored the efficacy and safety of tadekinig alpha (an IL-18 binding protein) in autoinflammatory conditions driven by IL-18 (Arnold) such as NLRC4 GOF and XIAP deficiency ( 125 ). Regarding IL-10 related VEO-IBD, IL-1 inhibitors have been suggested based on the assumption that IL-10 LOF mutations can interact with activation through the inflammasome which would lead to increased IL-1 levels ( 126 ). Abatacept (CTLA-4 fusion protein) is used in CTLA-4 and LRBA deficiencies ( 127 ).…”

“…Furthermore, limitations encompass the availability of compatible donors, the age of patients, and the severity of the disease and/or end-organ damage ( 118 ). Due to the importance of conditioning regimes for survival, HSCT recommendation guidelines are established by the EBMT/ESID inborn errors working party guidelines (IEWP) ( 118 , 126 , 133 ). PIRD has particular challenges for HSCT.…”

Unveiling the potential of galectin-3 as a diagnostic biomarker for pancreatic cancer: a review

“…Incorporating Gal-3 testing into pancreatic cancer management reflects the broader implications of precision medicine in improving patient outcomes. Precision medicine aims to tailor medical decisions and interventions to the individual characteristics of each patient, considering factors such as genetic makeup, molecular profiles, and environmental influences 71 . In pancreatic cancer, precision medicine holds tremendous potential to revolutionise treatment strategies and enhance overall management approaches 72 .…”