Immunodeficiency in DiGeorge Syndrome and Options for Treating Cases with Complete Athymia

Abstract

The commonest association of thymic stromal deficiency resulting in T-cell immunodeficiency is the DiGeorge syndrome (DGS). This results from abnormal development of the third and fourth pharyngeal arches and is most commonly associated with a microdeletion at chromosome 22q11 though other genetic and non-genetic causes have been described. The immunological competence of affected individuals is highly variable, ranging from normal to a severe combined immunodeficiency when there is complete athymia. In the most severe group, correction of the immunodeficiency can be achieved using thymus allografts which can support thymopoiesis even in the absence of donor-recipient matching at the major histocompatibility loci. This review focuses on the causes of DGS, the immunological features of the disorder, and the approaches to correction of the immunodeficiency including the use of thymus transplantation.

FOXN1 Deficiency: from the Discovery to Novel Therapeutic Approaches

“…Restoring a functional thymic stromal environment is expected to provide a long-lasting immune reconstitution [3,4]. In complete DiGeorge syndrome, it has been observed that HSCT did not result in a high-quality immune reconstitution [22,[58][59][60][61].…”

Disseminated Mycobacterium kansasii Disease in Complete DiGeorge Syndrome

“…Thymic transplantation ideally should be performed immediately after diagnosis of cDGS to facilitate T cell maturation [1]. If it must be delayed, patients may benefit from expansion of prophylaxis to include coverage for mycobacteria.…”

“…A minority (<1 %) have complete thymic aplasia, also known as Bcomplete^DGS (cDGS) [1]. Complete DGS is usually defined as <50 naïve (CD45RA + , CD62L + ) CD3 T cells/cc 3 and very low or absent mitogen response [1,2].…”

“…Those with cDGS are generally kept in isolation and receive regular intravenous immunoglobulin infusions. Thymic transplantation results in a normal host-derived T cell repertoire and has become the treatment of choice for cDGS [1]. Many patients receive antibiotic prophylaxis for Pneumocystis jirovecii infections, but it has not been common practice to do the same for nontuberculous mycobacterium (NTM) infections.…”

Transplanted human thymus slices induce and support T‐cell development in mice after cryopreservation

“…Infants born without a thymus require urgent treatment to reconstitute T‐cell immunity 1. Thymus tissue is removed from infants during cardiac surgery, to allow access to the heart.…”