Primary immunodeficiencies: a decade of shifting paradigms, the current status and the emergence of cutting-edge therapies and diagnostics

Abstract

A shift has occurred in the diagnostic and therapeutic modalities considered for patients with primary immunodeficiency diseases (PIDs). Early diagnosis remains the mainstay in appropriate management and remarkably influences the prognosis. More specific diagnostic tests as well as therapeutic modalities have been introduced in the last few decades. Nonetheless, the importance of a thorough history taking and physical examination should not be neglected. Novel diagnostic modalities including genetic sequencing have led to the recognition of previously unknown defects underlying PIDs. In addition, newborn screening is being advocated as an imperative diagnostic test. In terms of treatment, hematopoietic stem cell transplantation is considered the optimal treatment modality for many cases and has dramatically improved the outcome. Gene transfer into hematopoietic stem cells prior to transplantation has improved the efficacy of hematopoietic stem cell transplantation. In this article, the latest advances made in terms of diagnosis and treatment of PIDs are reviewed.

Approach to the Management of Autoimmunity in Primary Immunodeficiency

“…Ever since X‐linked agammaglobulinemia (XLA) was originally described in 1952, the number of independent PIDs has expanded and it now includes more than 300 entities. The principal groups of PIDs include (1) combined immunodeficiencies (CIDs), (2) CIDs with associated or syndromic features, (3) predominantly antibody deficiencies (PADs), (4) diseases of immune dysregulation, (5) congenital defects of phagocytosis, (6) defects in innate immunity, (7) autoinflammatory disorders, (8) complement deficiencies and (9) phenocopies of PID (Figure ) . Herein, we describe those groups of PIDs which are more associated with autoimmunity.…”

Advances in the Care of Primary Immunodeficiencies (PIDs): from Birth to Adulthood

“…This may involve the use of anti-infectious prophylaxis and the aggressive treatment of infections; however, for most patients with antibody deficiency, the cornerstone of therapy is immunoglobulin replacement therapy, the goal of which is to prevent most infections [18, 42–44]. Many studies show that immunoglobulin replacement therapy significantly reduces the rate of acute and chronic infection and greatly improves survival.…”

“…Many PIDs emerge in childhood; and with improved therapeutic options, life expectancy for patients with PIDs has increased in recent years [13, 42]. This means that many more PID patients now transition from pediatric to adult healthcare services, leading to a greater emphasis on the importance of the transition process.…”

Current Transition Practice for Primary Immunodeficiencies and Autoinflammatory Diseases in Europe: a RITA-ERN Survey

“…The majority of AID and more severe forms of PID manifest in childhood although additional manifestations and new complications occur over life. Marked improvements in the diagnosis and management of PID and AID in the last decades have improved the outlook for many patients, but at the same time bring new challenges to the care of these patients-many of whom have multimorbidity [5][6][7]. This modification of the natural history of the disease is associated with an increased survival of pediatric patients with PID and AID, who now need transfer to adult services for life-long follow-up [8] Therefore, a well-established interdisciplinary transition protocol is considered a standard of care for these patients and their families' needs to be carefully planned and managed [9].…”