Immunologic reconstitution in 22q deletion (DiGeorge) syndrome
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Immunologic reconstitution in 22q deletion (DiGeorge) syndrome Sean A. McGhee Æ Maria Garcia Lloret Æ E. Richard Stiehm
Published online: 24 February 2009 Ó Springer Science+Business Media, LLC 2009
Abstract Adoptive transfer of mature T cells (ATMTC) through bone marrow (BM) transplantation, first attempted over 20 years ago, has recently emerged as a successful therapy for complete 22q deletion syndrome (22qDS). This provides a potential option to thymic transplantation (TT) for immune reconstitution in 22qDS. Compared to thymic transplant, ATMTC is an easier procedure to accomplish and is available at more centers. However, there are differences in the nature of the T-cell reconstitution that results. Predictably, more naı¨ve T cells and recent thymic emigrants are present in patients treated with thymus transplant. There are no significant differences in mortality between the two procedures, but the number of patients is too limited to conclude that the procedures are equally effective. Adoptive transfer should be pursued as a reasonable treatment for 22qDS patients requiring immune reconstitution when thymus transplant is not available. Keywords DiGeorge syndrome Bone marrow transplantation Thymus transplantation T-cell immune deficiency Adoptive transfer
Introduction 22q deletion syndrome (22qDS), also known as DiGeorge syndrome (DGS), is most commonly caused by a hemizygous deletion on chromosome 22, resulting in haploinsufficiency of TBX1, a gene with a key role in the development of the pharyngeal arches. Children with 22qDS can present with variable clinical features, but frequently have hypoparathyroidism, abnormalities of the aortic arch and cardiac outflow tract, cleft palate, feeding disorders, mental retardation, and schizophrenia [1]. Although a mild T-cell deficiency is common, a few patients present with profound T-cell lymphopenia secondary to the severely impaired thymic function. These infants, suffering from what is known as complete DGS, are at risk of succumbing to widespread viral and opportunistic infections. S. A. McGhee M. G. Lloret (&) E. R. Stiehm Department of Pediatrics, Division of Pediatric Immunology, David Geffen School of Medicine at UCLA, MDCC 12-430 Los Angeles, CA 90095-1752, USA e-mail: [email protected]
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Immunol Res (2009) 45:37–45
The T-cell lymphopenia is thought to be caused by the failure of the thymus to properly form, preventing positive selection of developing T cells. The other features of 22qDS can be corrected with cardiac surgery, calcium supplementation and gavage feeding and, therefore long-term survival of 22qDS patients is now increasingly common. However, the athymia remains difficult to manage. Multiple different strategies have been attempted for immune reconstitution in 22qDS, including bone marrow (BM), cord blood (CB), peripheral blood mononuclear cell (PBMC), and thymic transplantation (TT). The immunodeficiency in 22qDS is unusual among T-cell disorders in that it is a failure of the matrix in which the T cell develops, rathe
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