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

Davies EG - Front Immunol (2013)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Centre for Immunodeficiency, Institute of Child Health, University College London and Great Ormond Street Hospital , London , UK.

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.

No MeSH data available.


Related in: MedlinePlus

T-cell receptor spectratyping performed as in legend to Figure 1. Same patient as in Figure 1, 23 months after thymus transplantation. Much more normal spectratype. All families represented mostly with Gaussian distribution.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3814041&req=5

Figure 2: T-cell receptor spectratyping performed as in legend to Figure 1. Same patient as in Figure 1, 23 months after thymus transplantation. Much more normal spectratype. All families represented mostly with Gaussian distribution.

Mentions: In the typical form of cDGS the T-cell numbers are <50/cumm and mitogen responses are absent. B cells are usually present in normal numbers and NK cells in normal or high numbers. In a proportion of cases there may be some mature T cells present either through maternal engraftment (94) or through oligoclonal expansion of memory phenotype T cells which have developed without thymic processing (95). In the latter case, as in SCID these cells can mediate severe inflammation leading to an Omenn-like picture with erythrodermic rashes, enteropathy, and lymphadenopathy (53, 96) This is called atypical cDGS. The diagnosis of complete athymia then depends on showing absence (<50/cumm) of T cells with a naïve (CD3 + CD45 RA+CD62L+) phenotype as well as abnormal T-cell receptor usage either by T-cell receptor spectratyping or FACS analysis of usage of V Beta TCR chains (96). An example of the abnormal spectratype in an atypical cDGS patient is shown in Figure 1 which can be compared to the normal spectratype achieved in the same patient after successful thymus transplantation (Figure 2). Mitogen responsiveness is usually, but not invariably, impaired in these atypical patients (96).


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

Davies EG - Front Immunol (2013)

T-cell receptor spectratyping performed as in legend to Figure 1. Same patient as in Figure 1, 23 months after thymus transplantation. Much more normal spectratype. All families represented mostly with Gaussian distribution.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3814041&req=5

Figure 2: T-cell receptor spectratyping performed as in legend to Figure 1. Same patient as in Figure 1, 23 months after thymus transplantation. Much more normal spectratype. All families represented mostly with Gaussian distribution.
Mentions: In the typical form of cDGS the T-cell numbers are <50/cumm and mitogen responses are absent. B cells are usually present in normal numbers and NK cells in normal or high numbers. In a proportion of cases there may be some mature T cells present either through maternal engraftment (94) or through oligoclonal expansion of memory phenotype T cells which have developed without thymic processing (95). In the latter case, as in SCID these cells can mediate severe inflammation leading to an Omenn-like picture with erythrodermic rashes, enteropathy, and lymphadenopathy (53, 96) This is called atypical cDGS. The diagnosis of complete athymia then depends on showing absence (<50/cumm) of T cells with a naïve (CD3 + CD45 RA+CD62L+) phenotype as well as abnormal T-cell receptor usage either by T-cell receptor spectratyping or FACS analysis of usage of V Beta TCR chains (96). An example of the abnormal spectratype in an atypical cDGS patient is shown in Figure 1 which can be compared to the normal spectratype achieved in the same patient after successful thymus transplantation (Figure 2). Mitogen responsiveness is usually, but not invariably, impaired in these atypical patients (96).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Centre for Immunodeficiency, Institute of Child Health, University College London and Great Ormond Street Hospital , London , UK.

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.

No MeSH data available.


Related in: MedlinePlus