Severe combined immunodeficiencies and related disorders.

Abstract

Severe combined immunodeficiencies (SCIDs) comprise a group of rare, monogenic diseases that are characterized by an early onset and a profound block in the development of T lymphocytes. Given that adaptive immunity is abrogated, patients with SCID are prone to recurrent infections caused by both non-opportunistic and opportunistic pathogens, leading to early death unless immunity can be restored. Several molecular defects causing SCIDs have been identified, along with many other defects causing profound, albeit incomplete, T cell immunodeficiencies; the latter are referred to as atypical SCIDs or combined immunodeficiencies. The pathophysiology of many of these conditions has now been characterized. Early, accurate and precise diagnosis combined with the ongoing implementation of newborn screening have enabled major advances in the care of infants with SCID, including better outcomes of allogeneic haematopoietic stem cell transplantation. Gene therapy is also becoming an effective option. Further advances and a progressive extension of the indications for gene therapy can be expected in the future. The assessment of long-term outcomes of patients with SCID is now a major challenge, with a view to evaluating the quality and sustainability of immune restoration, the risks of sequelae and the ability to relieve the non-haematopoietic syndromic manifestations that accompany some of these conditions.