The Experts below are selected from a list of 291 Experts worldwide ranked by ideXlab platform
Kathleen E Sullivan - One of the best experts on this subject based on the ideXlab platform.
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Immunoglobulin Deficiencies: The B-Lymphocyte Side of DiGeorge Syndrome
The Journal of pediatrics, 2012Co-Authors: Kiran Patel, Javeed Akhter, Lisa Kobrynski, Benjamin Gathman, Onika Davis, Kathleen E SullivanAbstract:DiGeorge Syndrome is associated with a T-lymphocyte immunodeficiency. The prevalence of hypogammaglobulinemia has not been reported. We found that 3% of patients with DiGeorge Syndrome were receiving immunoglobulin replacement therapy and 6% of patients over the age of 3 years had hypogammaglobulinemia. We conclude that DiGeorge Syndrome is associated with significant humoral immune deficiency.
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chromosome 22q11 2 deletion Syndrome DiGeorge Syndrome velocardiofacial Syndrome
Medicine, 2011Co-Authors: Donna M Mcdonaldmcginn, Kathleen E SullivanAbstract:AbstractChromosome 22q11.2 deletion Syndrome is a common Syndrome also known as DiGeorge Syndrome and velocardiofacial Syndrome. It occurs in approximately 1:4000 births, and the incidence is increasing due to affected parents bearing their own affected children. The manifestations of this Syndrome
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DiGeorge Syndrome/chromosome 22q11.2 deletion Syndrome
Current allergy and asthma reports, 2001Co-Authors: Kathleen E SullivanAbstract:DiGeorge Syndrome is characterized by conotruncal cardiac defects, hypocalcemia, and a hypoplastic thymus. Many, but not all, patients have a heterozygous deletion of chromosome 22q11.2. In its most severe form, it represents a devastating Syndrome with high mortality. Patients with severe immunodeficiendy are candidates for a thymic transplant or a fully matched bone marrow transplant. Fortunately, the majority of patients with either DiGeorge Syndrome or chromosome 22q11.2 deletion Syndrome have a mild to moderate immunodeficiency. These patients may develop recurrent infections or autoimmune disease.
M. Louise Markert - One of the best experts on this subject based on the ideXlab platform.
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Disseminated Mycobacterium kansasii disease in complete DiGeorge Syndrome.
Journal of clinical immunology, 2015Co-Authors: Suellen Moli Yin, M. Louise Markert, Ronald M. Ferdman, Larry Wang, Jonathan S. TamAbstract:Purpose Complete DiGeorge Syndrome (cDGS) describes a subset of patients with DiGeorge Syndrome that have thymic aplasia, and thus are at risk for severe opportunistic infections. Patients with cDGS and mycobacterial infection have not previously been described. We present this case to illustrate that patients with cDGS are at risk for nontuberculous mycobacterial infections and to discuss further antimicrobial prophylaxis prior to thymic transplantation.
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Thymic transplantation for complete DiGeorge Syndrome: medical and surgical considerations.
Journal of pediatric surgery, 2004Co-Authors: Henry E. Rice, Laura P. Hale, Michael A. Skinner, Samuel M. Mahaffey, Keith T. Oldham, Richard J. Ing, M. Louise MarkertAbstract:Abstract Background/purpose Complete DiGeorge Syndrome results in the absence of functional T cells. Our program supports the transplantation of allogeneic thymic tissue in infants with DiGeorge Syndrome to reconstitute immune function. This study reviews the multidisciplinary care of these complex infants. Methods From 1991 to 2001, the authors evaluated 16 infants with complete DiGeorge Syndrome. All infants received multidisciplinary medical and surgical support. Clinical records for the group were reviewed. Results Four infants died without receiving a thymic transplantation, and 12 children survived to transplantation. The mean age at time of transplantation was 2.7 months (range, 1.1 to 4.4 months). All 16 infants had significant comorbidity including congenital heart disease (16 of 16), hypocalcemia (14 of 16), gastroesophageal reflux disease or aspiration (13 of 16), CHARGE complex (4 of 16), and other organ involvement (14 of 16). Nontransplant surgical procedures included central line placement (15 of 16), fundoplication or gastrostomy (10 of 16), cardiac repair (10 of 16), bronchoscopy or tracheostomy (6 of 16), and other procedures (12 of 16). Complications were substantial, and 5 of the 12 transplanted infants died of nontransplant-related conditions. All surviving infants have immune reconstitution, with follow-up from 2 to 10 years. Conclusions Although the transplantation of thymic tissue can restore immune function in infants with complete DiGeorge Syndrome, these children have substantial comorbidity. Care of these children requires coordinated multidisciplinary support.
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Transplantation of Thymus Tissue in Complete DiGeorge Syndrome
The New England journal of medicine, 1999Co-Authors: M. Louise Markert, Andreas Boeck, Laura P. Hale, Amy Kloster, Tanya M. Mclaughlin, Milena N. Batchvarova, Daniel C. Douek, Richard A. Koup, Donna D. Kostyu, Frances E. WardAbstract:Background The DiGeorge Syndrome is a congenital disorder that affects the heart, parathyroid glands, and thymus. In complete DiGeorge Syndrome, patients have severely reduced T-cell function. Methods We treated five infants (age, one to four months) with complete DiGeorge Syndrome by transplantation of cultured postnatal thymus tissue. Follow-up evaluations included immune phenotyping and proliferative studies of peripheral-blood mononuclear cells plus biopsy of the thymus allograft. Thymic production of new T cells was assessed in peripheral blood by tests for T-cell–receptor recombination excision circles, which are formed from excised DNA during the rearrangement of T-cell–receptor genes. Results After the transplantation of thymus tissue, T-cell proliferative responses to mitogens developed in four of the five patients. Two of the patients survived with restoration of immune function; three patients died from infection or abnormalities unrelated to transplantation. Biopsies of grafted thymus in the s...
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Possible extrathymic development of nonfunctional T cells in a patient with complete DiGeorge Syndrome.
Clinical immunology (Orlando Fla.), 1999Co-Authors: Harold R. Collard, Sherrie E. Schiff, Andreas Boeck, Laura P. Hale, Tanya M. Mc Laughlin, Theresa J. Watson, M. Louise MarkertAbstract:Complete DiGeorge Syndrome is characterized by the clinical triad of cardiac malformation, hypocalcemia, and T cell immunodeficiency due to congenital athymia. We describe an infant with complete DiGeorge Syndrome who at presentation had no circulating T cells detectable by flow cytometry. The patient spontaneously developed circulating T cells but these cells did not proliferate in response to mitogens. The T cell receptor Vbeta repertoire was severely restricted. All T cells were host, not maternal, as assessed by fluorescent in situ hybridization evaluation of 22q11 hemizygosity. At autopsy, this patient had no grossly detectable thymus tissue and no microscopic evidence for thymopoiesis. These findings suggest that appearance of T cells in infants with complete DiGeorge Syndrome may represent oligoclonal expansions of a small number of T cells that may have matured extrathymically and which do not respond in vitro to mitogen stimulation.
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Complete DiGeorge Syndrome: Persistence of profound immunodeficiency
The Journal of pediatrics, 1998Co-Authors: M. Louise Markert, Donna S. Hummell, Howard M. Rosenblatt, Sherrie E. Schiff, Terry O. Harville, Larry W. Williams, Richard I. Schiff, Rebecca H. BuckleyAbstract:Abstract Objective: DiGeorge Syndrome is characterized by developmental defects of the heart, parathyroid glands, and thymus. The objective of this study was to determine whether T-cell function spontaneously improves in patients with DiGeorge Syndrome who have profoundly depressed T-cell proliferative responses to mitogens at presentation, regardless of the T-cell count. Study design: We conducted a retrospective chart review of eight patients with DiGeorge Syndrome who had no proliferative responses to mitogens on presentation. Results: Despite lack of responsiveness of the patients' peripheral blood lymphocytes to mitogens, T cells were occasionally detected, and the patients' cells often responded to IL-2 and in mixed lymphocyte reactions. Unresponsiveness to mitogens and clinical immunodeficiency persisted without immune-based therapy. One patient is alive and well after immunoreconstitution from thymic transplantation. The others either died early of complications of their disease such as gastroesophageal reflux with aspiration (2 patients) or infection (2 patients) or died after attempts at immunorestorative therapy with IL-2, thymus transplantation, or bone marrow transplantation (3 patients). Conclusion: Eight patients with DiGeorge Syndrome who were first seen with no mitogen responsiveness did not improve spontaneously. We recommend HLA-identical bone marrow transplantation or thymic transplantation for these patients as soon as the diagnosis is confirmed. (J Pediatr 1998;132:15-21)
Laura P. Hale - One of the best experts on this subject based on the ideXlab platform.
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complete DiGeorge Syndrome development of rash lymphadenopathy and oligoclonal t cells in 5 cases
The Journal of Allergy and Clinical Immunology, 2004Co-Authors: Louise M Markert, Laura P. Hale, Marcella Sarzotti, Daniel A Ozaki, Gregory D Sempowski, Maria E Rhein, Marilyn J Alexieff, Blythe H Devlin, Paul Szabolcs, Rebecca H. BuckleyAbstract:Abstract Background Five patients with DiGeorge Syndrome presented with infections, skin rashes, and lymphadenopathy after the newborn period. T-cell counts and function varied greatly in each patient. Initial laboratory testing did not suggest athymia in these patients. Objective The purpose of this study was to determine whether the patients had significant immunodeficiency. Methods Research testing of peripheral blood included immunoscope evaluation of T-cell receptor β variable gene segment repertoire diversity, quantification of T-cell receptor rearrangement excision circles, and detection of naive T cells (expressing CD45RA and CD62L). Results The patients were classified as having DiGeorge Syndrome on the basis of syndromic associations and heart, parathyroid, and immune abnormalities. Immunoscope evaluation revealed that the T-cell repertoires were strikingly oligoclonal in all patients. There were few recent thymic emigrants, as indicated by the very low numbers of naive T cells ( 3 ) and the absence of T-cell receptor rearrangement excision circles. These studies showed that all 5 patients were athymic. Two patients died, one from infection. No thymus was found during the complete autopsy performed on one patient. Conclusion Patients with DiGeorge Syndrome, skin rash, and lymphadenopathy should undergo analysis of naive T-cell numbers and of T-cell receptor β variability segment repertoire to determine whether they are athymic, even if they have T cells with mitogen responsiveness. It is important for physicians to realize that patients with complete DiGeorge Syndrome remain profoundly immunodeficient after development of these atypical features (rash, lymphadenopathy, and oligoclonal T cells). Prompt diagnosis is necessary for appropriate management.
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Thymic transplantation for complete DiGeorge Syndrome: medical and surgical considerations.
Journal of pediatric surgery, 2004Co-Authors: Henry E. Rice, Laura P. Hale, Michael A. Skinner, Samuel M. Mahaffey, Keith T. Oldham, Richard J. Ing, M. Louise MarkertAbstract:Abstract Background/purpose Complete DiGeorge Syndrome results in the absence of functional T cells. Our program supports the transplantation of allogeneic thymic tissue in infants with DiGeorge Syndrome to reconstitute immune function. This study reviews the multidisciplinary care of these complex infants. Methods From 1991 to 2001, the authors evaluated 16 infants with complete DiGeorge Syndrome. All infants received multidisciplinary medical and surgical support. Clinical records for the group were reviewed. Results Four infants died without receiving a thymic transplantation, and 12 children survived to transplantation. The mean age at time of transplantation was 2.7 months (range, 1.1 to 4.4 months). All 16 infants had significant comorbidity including congenital heart disease (16 of 16), hypocalcemia (14 of 16), gastroesophageal reflux disease or aspiration (13 of 16), CHARGE complex (4 of 16), and other organ involvement (14 of 16). Nontransplant surgical procedures included central line placement (15 of 16), fundoplication or gastrostomy (10 of 16), cardiac repair (10 of 16), bronchoscopy or tracheostomy (6 of 16), and other procedures (12 of 16). Complications were substantial, and 5 of the 12 transplanted infants died of nontransplant-related conditions. All surviving infants have immune reconstitution, with follow-up from 2 to 10 years. Conclusions Although the transplantation of thymic tissue can restore immune function in infants with complete DiGeorge Syndrome, these children have substantial comorbidity. Care of these children requires coordinated multidisciplinary support.
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thymus transplantation in complete DiGeorge Syndrome immunologic and safety evaluations in 12 patients
Blood, 2003Co-Authors: Louise M Markert, Laura P. Hale, Marcella Sarzotti, Daniel A Ozaki, Gregory D Sempowski, Maria E Rhein, Francoise Le Deist, Marilyn J Alexieff, Elizabeth R Hauser, Barton F HaynesAbstract:Complete DiGeorge Syndrome is a fatal condition in which infants have no detectable thymus function. The optimal treatment for the immune deficiency of complete DiGeorge Syndrome has not been determined. Safety and efficacy of thymus transplantation were evaluated in 12 infants with complete DiGeorge Syndrome who had less than 20-fold proliferative responses to phytohemagglutinin. All but one had fewer than 50 T cells/mm3. Allogeneic postnatal cultured thymus tissue was transplanted. T-cell development was followed by flow cytometry, lymphocyte proliferation assays, and T-cell receptor Vbeta (TCRBV) repertoire evaluation. Of the 12 patients, 7 are at home 15 months to 8.5 years after transplantation. All 7 survivors developed T-cell proliferative responses to mitogens of more than 100 000 counts per minute (cpm). By one year after transplantation, 6 of 7 patients developed antigen-specific proliferative responses. The TCRBV repertoire showed initial oligoclonality that progressed to polyclonality within a year. B-cell function developed in all 3 patients tested after 2 years. Deaths were associated with underlying congenital problems. Risk factors for death included tracheostomy, long-term mechanical ventilation, and cytomegalovirus infection. Adverse events in the first 3 months after transplantation included eosinophilia, rash, lymphadenopathy, development of CD4-CD8- peripheral T cells, elevated serum immunoglobulin E (IgE), and possible pulmonary inflammation. Adverse events related to the immune system occurring more than 3 months after transplantation included thrombocytopenia in one patient and hypothyroidism and alopecia in one other patient. Thymic transplantation is efficacious, well tolerated, and should be considered as treatment for infants with complete DiGeorge Syndrome.
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Transplantation of Thymus Tissue in Complete DiGeorge Syndrome
The New England journal of medicine, 1999Co-Authors: M. Louise Markert, Andreas Boeck, Laura P. Hale, Amy Kloster, Tanya M. Mclaughlin, Milena N. Batchvarova, Daniel C. Douek, Richard A. Koup, Donna D. Kostyu, Frances E. WardAbstract:Background The DiGeorge Syndrome is a congenital disorder that affects the heart, parathyroid glands, and thymus. In complete DiGeorge Syndrome, patients have severely reduced T-cell function. Methods We treated five infants (age, one to four months) with complete DiGeorge Syndrome by transplantation of cultured postnatal thymus tissue. Follow-up evaluations included immune phenotyping and proliferative studies of peripheral-blood mononuclear cells plus biopsy of the thymus allograft. Thymic production of new T cells was assessed in peripheral blood by tests for T-cell–receptor recombination excision circles, which are formed from excised DNA during the rearrangement of T-cell–receptor genes. Results After the transplantation of thymus tissue, T-cell proliferative responses to mitogens developed in four of the five patients. Two of the patients survived with restoration of immune function; three patients died from infection or abnormalities unrelated to transplantation. Biopsies of grafted thymus in the s...
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Possible extrathymic development of nonfunctional T cells in a patient with complete DiGeorge Syndrome.
Clinical immunology (Orlando Fla.), 1999Co-Authors: Harold R. Collard, Sherrie E. Schiff, Andreas Boeck, Laura P. Hale, Tanya M. Mc Laughlin, Theresa J. Watson, M. Louise MarkertAbstract:Complete DiGeorge Syndrome is characterized by the clinical triad of cardiac malformation, hypocalcemia, and T cell immunodeficiency due to congenital athymia. We describe an infant with complete DiGeorge Syndrome who at presentation had no circulating T cells detectable by flow cytometry. The patient spontaneously developed circulating T cells but these cells did not proliferate in response to mitogens. The T cell receptor Vbeta repertoire was severely restricted. All T cells were host, not maternal, as assessed by fluorescent in situ hybridization evaluation of 22q11 hemizygosity. At autopsy, this patient had no grossly detectable thymus tissue and no microscopic evidence for thymopoiesis. These findings suggest that appearance of T cells in infants with complete DiGeorge Syndrome may represent oligoclonal expansions of a small number of T cells that may have matured extrathymically and which do not respond in vitro to mitogen stimulation.
P. Lopes - One of the best experts on this subject based on the ideXlab platform.
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DiGeorge Syndrome with total monosomy 22 diagnosed prenatally.
Prenatal diagnosis, 1995Co-Authors: A. Merino, A. De Perdigo, F. Nomballais, M. Yyinec, P. LopesAbstract:A case of monosomy 22 diagnosed prenatally is reported. During pregnancy, ultrasonic observations already revealed several cardiac malformations of the fetus in the 25th week. Following counselling, the pregnancy was terminated. Fetal autopsy revealed several abnormalities associated with DiGeorge Syndrome.
Rebecca H. Buckley - One of the best experts on this subject based on the ideXlab platform.
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complete DiGeorge Syndrome development of rash lymphadenopathy and oligoclonal t cells in 5 cases
The Journal of Allergy and Clinical Immunology, 2004Co-Authors: Louise M Markert, Laura P. Hale, Marcella Sarzotti, Daniel A Ozaki, Gregory D Sempowski, Maria E Rhein, Marilyn J Alexieff, Blythe H Devlin, Paul Szabolcs, Rebecca H. BuckleyAbstract:Abstract Background Five patients with DiGeorge Syndrome presented with infections, skin rashes, and lymphadenopathy after the newborn period. T-cell counts and function varied greatly in each patient. Initial laboratory testing did not suggest athymia in these patients. Objective The purpose of this study was to determine whether the patients had significant immunodeficiency. Methods Research testing of peripheral blood included immunoscope evaluation of T-cell receptor β variable gene segment repertoire diversity, quantification of T-cell receptor rearrangement excision circles, and detection of naive T cells (expressing CD45RA and CD62L). Results The patients were classified as having DiGeorge Syndrome on the basis of syndromic associations and heart, parathyroid, and immune abnormalities. Immunoscope evaluation revealed that the T-cell repertoires were strikingly oligoclonal in all patients. There were few recent thymic emigrants, as indicated by the very low numbers of naive T cells ( 3 ) and the absence of T-cell receptor rearrangement excision circles. These studies showed that all 5 patients were athymic. Two patients died, one from infection. No thymus was found during the complete autopsy performed on one patient. Conclusion Patients with DiGeorge Syndrome, skin rash, and lymphadenopathy should undergo analysis of naive T-cell numbers and of T-cell receptor β variability segment repertoire to determine whether they are athymic, even if they have T cells with mitogen responsiveness. It is important for physicians to realize that patients with complete DiGeorge Syndrome remain profoundly immunodeficient after development of these atypical features (rash, lymphadenopathy, and oligoclonal T cells). Prompt diagnosis is necessary for appropriate management.
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Complete DiGeorge Syndrome: Persistence of profound immunodeficiency
The Journal of pediatrics, 1998Co-Authors: M. Louise Markert, Donna S. Hummell, Howard M. Rosenblatt, Sherrie E. Schiff, Terry O. Harville, Larry W. Williams, Richard I. Schiff, Rebecca H. BuckleyAbstract:Abstract Objective: DiGeorge Syndrome is characterized by developmental defects of the heart, parathyroid glands, and thymus. The objective of this study was to determine whether T-cell function spontaneously improves in patients with DiGeorge Syndrome who have profoundly depressed T-cell proliferative responses to mitogens at presentation, regardless of the T-cell count. Study design: We conducted a retrospective chart review of eight patients with DiGeorge Syndrome who had no proliferative responses to mitogens on presentation. Results: Despite lack of responsiveness of the patients' peripheral blood lymphocytes to mitogens, T cells were occasionally detected, and the patients' cells often responded to IL-2 and in mixed lymphocyte reactions. Unresponsiveness to mitogens and clinical immunodeficiency persisted without immune-based therapy. One patient is alive and well after immunoreconstitution from thymic transplantation. The others either died early of complications of their disease such as gastroesophageal reflux with aspiration (2 patients) or infection (2 patients) or died after attempts at immunorestorative therapy with IL-2, thymus transplantation, or bone marrow transplantation (3 patients). Conclusion: Eight patients with DiGeorge Syndrome who were first seen with no mitogen responsiveness did not improve spontaneously. We recommend HLA-identical bone marrow transplantation or thymic transplantation for these patients as soon as the diagnosis is confirmed. (J Pediatr 1998;132:15-21)