Successful restoration of immunity in the DiGeorge syndrome with fetal thymic epithelial transplant.

Thong, Y.H.; Robertson, Evelyn F.; Rischbieth, Harold; Smith, Gregory J.; Binns, Gregory F.; Cheney, Kelly M.; Pollard, A.C.

doi:10.1136/adc.53.7.580

Cited by 27 publications

(7 citation statements)

References 18 publications

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“…Before positive selection had arrived on the scene, Miller and Mitchel did their classic experiments showing that T cells were required for the production of antibody using T and B cells from different strains of mice (Miller & Mitchel 1968)! And in the meantime, surgeons were curing Di George patients with allogeneic fetal thymus epitheiium grafts, blithly ignoring the vast majority of immunologists who would predict that it cannot work (Thong et al 1978). So, given that the two theoretical frameworks exist, that neither is perfect, and that both seem to generate ideas and experiments, is there any clear way to distinguish between them?…”

Section: Epilogue: An Experimental Oeeeringmentioning

confidence: 99%

Why Positive Selection?

Matzinger

1993

Immunological Reviews

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Section: Epilogue: An Experimental Oeeeringmentioning

confidence: 99%

Why Positive Selection?

Matzinger

1993

Immunological Reviews

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“…These findings correlate with clinical observa tions of increased susceptibility to infection in general [19], and the higher morbidity and mortality with res piratory syncytial viral infections in particular [18], Our own clinical experience shows that, overall, al most half of the patients enter hospital for infections, and that the conotruncal group, which is more immunodeficient than the shunt group, has a cor respondingly higher prevalence of infections. These findings indicate that immunological assessment should be considered for children with congenital heart disease, especially those with conotruncal malformations, since T cell immunodeficiencies are amenable to therapy with thymic-epithelial trans plantation [22,23], or thymic-hormone therapy [24], and immunoglobulin deficiencies are amenable to gammaglobulin supplementation [25],…”

Section: Discussionmentioning

confidence: 99%

The Immunocompetence of Children with Congenital Heart Disease

Radford

Lachman

Thong

1986

Int Arch Allergy Immunol

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We studied the immunocompetence of 18 children with conotruncal malformations (13 with tetralogy of Fallot, 5 with truncus arteriosus) and 22 children with cardiac shunt lesions. There were reduced total T cell percentages and T helper cells in the conotruncal group but no T cell abnormality in the shunt group. Also, 7 of the 18 cases in the conotruncal group had facial dysmorphism reminiscent of the Di George syndrome. These results suggest that patients with conotruncal malformations fall into the wide spectrum of the Di George syndrome. There was some humoral deficiency in both groups with reduced levels of immunoglobulins IgG and IgA and low levels of complement C3 and C4. The clinical records showed a high frequency of infections. Hospital admissions for these episodes had occurred in 61 % of the conotruncal group and 32% of the shunt group. Thus, there is an increased susceptibility to infection in children with congenital heart disease, and the predilection to infection has an immunological basis.

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“…2 Therapies for the immunodeficient type of this syndrome have been fetal thymus transplantation, thymic hormone administration and bone marrow transplantation (BMT). For thymic transplantation, it is necessary to use fetal thymic tissue 3 or to use cultured thymic epithelial tissue, since it is not as easy to get donor cells. For thymic hormones such as thymosin, thymopoietin and thymulin, it is unclear what nature of thymic hormones should be used and over what time period, results have varied.…”

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Complete-type DiGeorge syndrome treated by bone marrow transplantation

Matsumoto

Amamoto

Kondoh

et al. 1998

Bone Marrow Transplant

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Summary:BMT was carried out on a patient with DiGeorge syndrome who suffered recurrent infections after birth. At 13 months of age, 8.0 × 10 8 /kg of bone marrow nuclear cells were infused from an HLA-identical sibling using only anti-thymocyte globulin to prevent rejection. Donor DNA was not detected on microsatellite polymorphism by PCR. At 19 months of age, a second BMT from the same donor was carried out using busulfan and cyclophosphamide as conditioning. DNA examination of bone marrow showed chimerism at day 18 and complete donor origin at day 28. Seven months post-BMT, the numbers of CD3-, CD4-and CD8-positive cells were in the normal range. BMT is thus an effective therapy for DiGeorge syndrome. Keywords: DiGeorge syndrome; complete type; immunodeficiency; bone marrow transplantation DiGeorge syndrome (DGS) is characterized by dysmorphic faces, congenital heart disease, hypocalcemia and T cell dysfunction due to aplasia of the thymus. 1 Although confirmation of aplasia of the thymus is difficult, it is clinically classified as complete or incomplete; the former manifests with cellular immunodeficiency and the latter does not. 2 Therapies for the immunodeficient type of this syndrome have been fetal thymus transplantation, thymic hormone administration and bone marrow transplantation (BMT). For thymic transplantation, it is necessary to use fetal thymic tissue 3 or to use cultured thymic epithelial tissue, since it is not as easy to get donor cells. For thymic hormones such as thymosin, thymopoietin and thymulin, it is unclear what nature of thymic hormones should be used and over what time period, results have varied. 4 BMT has been attempted for DGS in seven patients 5 and two of these underwent transplantation without any pre-conditioning, with favourable results. 6,7 Here, we report a patient with complete-type DGS treated with BMT who exhibited reconstitution of T cell immunity.Correspondence: T Matsumoto, Department of Pediatrics, Nagasaki University School of Medicine, Sakamoto 1-7-1, Nagasaki 852, Japan Received 6 February 1998; accepted 8 July 1998 Case reportA boy was born at 39 weeks gestation with an Apgar score of 7. His birth weight was 3275 g. There were no special events during gestation except for polyhydramion. Family history was negative. He showed cyanosis after birth and respiratory arrest occurred at day 6 probably due to hypocalcemia, and he was referred to the National Nagasaki Central Hospital. He showed the characteristic facial features such as a hypertelorism, narrowed palpebral fissures, low set ears, deformity of both ear helices, anteverted nostrils, a shortened philtrum, micrognathia and a high arched palate. He had hypocalcemia with a low plasma level of parathyroid hormone. Chest X-ray, ultrasound and computed tomography (CT) showed no thymus-like components. Echocardiogram and cardiac catheterization revealed tetralgy of Fallot. He failed to thrive, and showed a tendency towards infection after admission, including repeated episodes of fever and continuous presence of ec...

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Successful restoration of immunity in the DiGeorge syndrome with fetal thymic epithelial transplant.

Cited by 27 publications

References 18 publications

Why Positive Selection?

Why Positive Selection?

The Immunocompetence of Children with Congenital Heart Disease

Complete-type DiGeorge syndrome treated by bone marrow transplantation

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