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12 - Immunodeficiency diseases of the neonate

Published online by Cambridge University Press:  10 August 2009

Pedro A. de Alarcón
Affiliation:
University of Tennessee
Eric J. Werner
Affiliation:
Eastern Virginia Medical School
J. Lawrence Naiman
Affiliation:
Stanford University School of Medicine, California
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Summary

Introduction

Significant progress has been made towards the understanding of the clinical implications of the neonatal immune system and its immaturity. With the increasing survival of extremely premature infants, neonatologists and other physicians caring for these patients must be aware of the vulnerability of this select patient population. It is also important for neonatologists and pediatricians to be able to differentiate between immune immaturity and a true primary immunodeficiency that may present during the neonatal period. Failure to identify properly primary immunodeficiency diseases can result in delayed diagnosis and treatment, which can significantly affect the outcome of the disease. This chapter defines the immune immaturity of the neonate and how it impacts susceptibility to neonatal infection. It will describe the specific immune deficiency syndromes that may present during the neonatal period. Finally, the diagnosis and management of neonatal immunodeficiency diseases will be discussed in length in order to provide the reader with the proper approach and management guidelines to care adequately for these individuals.

Immaturity of the neonatal immune system

The immaturity of a neonate's immune response places the neonate at an increased risk for serious infection. An understanding of the development of the neonatal immune system is essential in order to be able to differentiate the clinical manifestations of infection associated with immaturity from those that identify a specific acquired or primary immunodeficiency disease. The focus of this section is to define how the immune immaturity of the neonate impacts susceptibility to infection.

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Neonatal Hematology , pp. 280 - 309
Publisher: Cambridge University Press
Print publication year: 2005

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References

Edwards, M. S., Buffone, G. J., Fuselier, P. A., Weeks, J. L., Baker, C. J.Deficient classical complement pathway activity in newborn sera. Pediatr Res 1983; 17: 685–688CrossRefGoogle ScholarPubMed
Geelen, S. P., Fleer, A., Bezemer, A. C., et al.Deficiencies in opsonic defense to pneumococci in the human newborn despite adequate levels of complement and specific IgG antibodies. Pediatr Res 1990; 27: 514–518CrossRefGoogle ScholarPubMed
Marodi, L., Leijh, P. C., Braat, A., Daha, M. R., Furth, R.Opsonic activity of cord blood sera against various species of microorganism. Pediatr Res 1985; 19: 433–436CrossRefGoogle ScholarPubMed
Mills, E. L., Bjorksten, B., Quie, P. G.Deficient alternative complement pathway activity in newborn sera. Pediatr Res 1979; 13: 1341–1344CrossRefGoogle ScholarPubMed
Barrett, D. J., Sleasman, J. W. Immunodeficiency disorders in infants and children. In Kass, E. H., Platt, R., eds. Current Therapy in Infectious Disease. Philadelphia: BC Decker, 1990: 51–68Google Scholar
Zach, T. L., Hostetter, M. K.Biochemical abnormalities of the third component of complement in neonates. Pediatr Res 1989; 26: 116–120CrossRefGoogle ScholarPubMed
Winkelstein, J. A., Kurlandsky, L. E., Swift, A. J.Defective activation of the third component of complement in the sera of newborn infants. Pediatr Res 1979; 13: 1093–1096CrossRefGoogle ScholarPubMed
Wilson, C. B., Lewis, D. B., Perix, L. A. The physiologic immunodeficiency of immaturity. In Stiehm, R. F. ed. Immunologic Disorders in Infants and Children, Vol. 1. Philadelphia: W. B. Saunders, 1996: 253–296Google Scholar
Berger, M.Complement deficiency and neutrophil dysfunction as risk factors for bacterial infection in newborns and the role of granulocyte transfusion in therapy. Rev Infect Dis 1990; 12 (Suppl 4): S401–S409CrossRefGoogle ScholarPubMed
Schelonka, R. L., Infante, A. J.Neonatal immunology. Semin Perinatol 1998; 22: 2–14CrossRefGoogle ScholarPubMed
Yoder, M. P. R. The immune system. In Avroy, A., Fanaroff, R. J. M., eds. Neonatal-Perinatal Medicine: Diseases of the Fetus and Infant, Vol. 1. St Louis: Mosby, 1997: 685–717Google Scholar
Colten, H. R.Ontogeny of the human complement system: in vitro biosynthesis of individual complement components by fetal tissues. J Clin Invest 1972; 51: 725–730CrossRefGoogle ScholarPubMed
Davis, C. A., Vallota, E. H., Forristal, J.Serum complement levels in infancy: age related changes. Pediatr Res 1979; 13: 1043–1046CrossRefGoogle ScholarPubMed
Barnard, D. R., Arthur, M. M.Fibronectin (cold insoluble globulin) in the neonate. J Pediatr 1983; 102: 453–455CrossRefGoogle ScholarPubMed
Yoder, M. C., Douglas, S. D., Gerdes, J., Kline, J., Polin, R. A.Plasma fibronectin in healthy newborn infants: respiratory distress syndrome and perinatal asphyxia. J Pediatr 1983; 102: 777–780CrossRefGoogle ScholarPubMed
Gerdes, J. S., Yoder, M. C., Douglas, S. D., Polin, R. A.Decreased plasma fibronectin in neonatal sepsis. Pediatrics 1983; 72: 877–881Google ScholarPubMed
Philip, A. G.Response of C-reactive protein in neonatal Group B streptococcal infection. Pediatr Infect Dis 1985; 4: 145–148CrossRefGoogle ScholarPubMed
Hill, H. R.Biochemical, structural, and functional abnormalities of polymorphonuclear leukocytes in the neonate. Pediatr Res 1987; 22: 375–382CrossRefGoogle ScholarPubMed
Ainbender, E., Cabatu, E. E., Guzman, D. M., Sweet, A. Y.Serum C-reactive protein and problems of newborn infants. J Pediatr 1982; 101: 438–440CrossRefGoogle ScholarPubMed
Summerfield, J. A., Sumiya, M., Levin, M., Turner, M. W.Association of mutations in mannose binding protein gene with childhood infection in consecutive hospital series. Br Med J 1997; 314: 1229–1232CrossRefGoogle ScholarPubMed
Lau, Y. L., Chan, S. Y., Turner, M. W., Fong, J., Karlberg, J.Mannose-binding protein in preterm infants: developmental profile and clinical significance. Clin Exp Immunol 1995; 102: 649–654CrossRefGoogle ScholarPubMed
Wilson, C. B., Lewis, D. B.Basis and implications of selectively diminished cytokine production in neonatal susceptibility to infection. Rev Infect Dis 1990; 12 (Suppl 4): S410–S420CrossRefGoogle ScholarPubMed
Dretschmer, R. R., Stewardson, R. B., Papierniak, C. K., Gotoff, S. P.Chemotactic and bactericidal capacities of human newborn monocytes. J Immunol 1976; 117: 1303–1307Google ScholarPubMed
Kilpatrick, L., Harris, M. C. Cytokine and the inflammatory response. In Polin, R. A., Fox, W. W., ed. Fetal and Neonatal Physiology. Philadelphia: W. B. Saunders, 1998: 1967–1980Google Scholar
Nesin, M., Cunningham-Rundles, S.Cytokines and neonates. Am J Perinatol 2000; 17: 393–404CrossRefGoogle ScholarPubMed
Wong, G. H., Goeddel, D. V.Tumour necrosis factors alpha and beta inhibit virus replication and synergize with interferons. Nature 1986; 323: 819–822CrossRefGoogle ScholarPubMed
Slayton, W. Development of the immune system in the human fetus. In Christensen, R., ed. Hematologic Problems of the Neonate. Philadelphia: W. B. Saunders, 2000: 21–41Google Scholar
Lin, H., Mosmann, T. R., Guilbert, L., Tuntipopipat, S., Wegmann, T. G.Synthesis of T helper 2-type cytokines at the maternal-fetal interface. J Immunol 1993; 151: 4562–4573Google Scholar
Formby, B.Immunologic response in pregnancy: its role in endocrine disorders of pregnancy and influence on the course of maternal autoimmune diseases. Endocrinol Metab Clin North Am 1995; 24: 187–205Google ScholarPubMed
Stallmach, T., Hebisch, G., Joller-Jemelka, H. I., et al.Cytokine production and visualized effects in the feto-maternal unit: quantitative and topographic data on cytokines during intrauterine disease. Lab Invest 1995; 73: 384–392Google ScholarPubMed
Luettichau, I., Nelson, P. J., Pattison, J. M., et al.RANTES chemokine expression in diseased and normal human tissues. Cytokine 1996; 8: 89–98CrossRefGoogle Scholar
Shimoya, K., Matsuzaki, N., Taniguchi, T., et al.Interleukin-8 in cord sera: a sensitive and specific marker for the detection of preterm chorioamnionitis. J Infect Dis 1992; 165: 957–960CrossRefGoogle ScholarPubMed
Zhou, P., Goldstein, S., Devadas, K., Tewari, D., Notkins, A. L.Human CD4+ cells transfected with IL-16 cDNA are resistant to HIV-1 infection: inhibition of mRNA expression. Nat Med 1997; 3: 659–664CrossRefGoogle ScholarPubMed
Lim, K. G., Wan, H. C., Bozza, P. T., et al.Human eosinophils elaborate the lymphocyte chemoattractants: IL-16 (lymphocyte chemoattractant factor) and RANTES. J Immunol 1996; 156: 2566–2570Google ScholarPubMed
Sorensen, R. U., Moore, C.Antibody deficiency syndromes. Pediatr Clin North Am 2000; 47: 1225–1252CrossRefGoogle ScholarPubMed
Schroeder, H. W. Jr, Zhang, L., Philips, J. B., , 3rd.Slow, programmed maturation of the immunoglobulin HCDR3 repertoire during the third trimester of fetal life. Blood 2001; 98: 2745–2751CrossRefGoogle ScholarPubMed
Owen, J. J., Cooper, M. D., Raff, M. C.In vitro generation of B lymphocytes in mouse foetal liver, a mammalian ‘bursa equivalent. Nature 1974; 249: 361–363CrossRefGoogle ScholarPubMed
DeBiagi, M., Andreani, M., Centis, F.Immune characterization of human fetal tissues with monoclonal antibodies. Prog Clin Biol Res 1985; 193: 89–94Google ScholarPubMed
Hayward, A. R., Ezer, G.Development of lymphocyte populations in the human foetal thymus and spleen. Clin Exp Immunol 1974; 17: 169–178Google ScholarPubMed
Gupta, S., Pahwa, R., O'Reilly, R., Good, R. A., Siegal, F. P.Ontogeny of lymphocyte subpopulations in human fetal liver. Proc Natl Acad Sci USA 1976; 73: 919–922CrossRefGoogle ScholarPubMed
Gathings, W. E., Lawton, A. R., Cooper, M. D.Immunofluorescent studies of the development of pre-B-cells, B lymphocytes and immunoglobulin isotype diversity in humans. Eur J Immunol 1977; 7: 804–810CrossRefGoogle ScholarPubMed
Gathings, W. E., Kubagawa, H., Cooper, M. D.A distinctive pattern of B-cell immaturity in perinatal humans. Immunol Rev 1981; 57: 107–126CrossRefGoogle ScholarPubMed
Schroeder, H. W. Jr, Hillson, J. L., Perlmutter, R. M.Early restriction of the human antibody repertoire. Science 1987; 238: 791–793CrossRefGoogle ScholarPubMed
Cuisinier, A. M., Guigou, V., Boubli, L., Fougereau, M., Tonnelle, C.Preferential expression of VH5 and VH6 immunoglobulin genes in early human B-cell ontogeny. Scand J Immunol 1989; 30: 493–497CrossRefGoogle ScholarPubMed
Ballow, M., Cates, K. L., Rowe, J. C., Goetz, C., Desbonnet, C.Development of the immune system in very low birth weight (less than 1500 g) premature infants: concentrations of plasma immunoglobulins and patterns of infections. Pediatr Res 1986; 20: 899–904CrossRefGoogle Scholar
Schaffer, F. M., Newton, J. A.Intravenous gamma globulin administration to common variable immunodeficient women during pregnancy: case report and review of the literature. J Perinatol 1994; 14: 114–117Google ScholarPubMed
Landor, M.Maternal-fetal transfer of immunoglobulins. Ann Allergy Asthma Immunol 1995; 74: 279–283, 284Google ScholarPubMed
Stiehm, E. R., Fudenberg, H. H.Serum levels of immune globulins in health and disease: a survey. Pediatrics 1966; 37: 715–727Google ScholarPubMed
Cederqvist, L. L., Ewool, L. C., Litwin, S. D.The effect of fetal age, birth weight, and sex on cord blood immunoglobulin values. Am J Obstet Gynecol 1978; 131: 520–525CrossRefGoogle Scholar
Alford, C. A. Jr, Stagno, S., Reynolds, D. W.Diagnosis of chronic perinatal infections. Am J Dis Child 1975; 129: 455–463Google ScholarPubMed
Griffiths, P. D., Stagno, S., Pass, R. F., Smith, R. J., Alford, C. A. Jr.Congenital cytomegalovirus infection: diagnostic and prognostic significance of the detection of specific immunoglobulin M antibodies in cord serum. Pediatrics 1982; 69: 544–549Google ScholarPubMed
Enders, G.Serologic test combinations for safe detection of rubella infections. Rev Infect Dis 1985; 7 (Suppl 1): S113–S122CrossRefGoogle ScholarPubMed
Naot, Y., Desmonts, G., Remington, J. S.IgM enzyme-linked immunosorbent assay test for the diagnosis of congenital Toxoplasma infection. J Pediatr 1981; 98: 32–36CrossRefGoogle Scholar
Leung, D. Y., Young, M. C., Geha, R. S.Secretion of IgE-specific potentiating factors by human Fc epsilon R+ T cell lines. Int Arch Allergy Appl Immunol 1985; 77: 232–234CrossRefGoogle ScholarPubMed
Morito, T., Bankhurst, A. D., Williams, R. C. Jr.Studies of human cord blood and adult lymphocyte interactions with in vitro immunoglobulin production. J Clin Invest 1979; 64: 990–995CrossRefGoogle ScholarPubMed
Nagaoki, T., Miyawaki, T., Ciorbaru, R., et al.Maturation of B-cell differentiation ability and T cell regulatory function during child growth assessed in a Nocardia water soluble mitogen-driven system. J Immunol 1981; 126: 2015–2019Google Scholar
Haynes, B. F., Martin, M. E., Kay, H. H., Kurtzberg, J.Early events in human T cell ontogeny: phenotypic characterization and immunohistologic localization of T cell precursors in early human fetal tissues. J Exp Med 1988; 168: 1061–1080CrossRefGoogle Scholar
Asma, G. E., Bergh, R. L., Vossen, J. M.Use of monoclonal antibodies in a study of the development of T lymphocytes in the human fetus. Clin Exp Immunol 1983; 53: 429–436Google Scholar
Campbell, A. C., Waller, C., Wood, J., Aynsley-Green, A., Yu, V.Lymphocyte subpopulations in the blood of newborn infants. Clin Exp Immunol 1974; 18: 469–482Google ScholarPubMed
Struyk, L., Howes, G. E., Raaphorst, F. M., et al. The human peripheral T-cell repertoire. In Elsen, P., ed. The Human T-Cell Receptor Repertoire and Transplantation. Austin, TX: RG Landes, 1995: 29–61CrossRefGoogle Scholar
Strauss, R. G.Data-driven blood banking practices for neonatal RBC transfusions. Transfusion 2000; 40: 1528–1540CrossRefGoogle ScholarPubMed
Lewis, D. B., Yu, C. C., Meyer, J., et al.Cellular and molecular mechanisms for reduced interleukin 4 and interferon-gamma production by neonatal T-cells. J Clin Invest 1991; 87: 194–202CrossRefGoogle ScholarPubMed
Pirenne-Ansart, H., Paillard, F., Groote, D., et al.Defective cytokine expression but adult-type T-cell receptor, CD8, and p56lck modulation in CD3- or CD2-activated T-cells from neonates. Pediatr Res 1995; 37: 64–69CrossRefGoogle ScholarPubMed
Splawski, J. B., Nishioka, J., Nishioka, Y., Lipsky, P. E.CD40 ligand is expressed and functional on activated neonatal T cells. J Immunol 1996; 156: 119–127Google ScholarPubMed
Durandy, A., Saint Basile, G., Lisowska-Grospierre, B., et al.Undetectable CD40 ligand expression on T cells and low B cell responses to CD40 binding agonists in human newborns. J Immunol 1995; 154: 1560–1568Google Scholar
Nonoyama, S., Penix, L. A., Edwards, C. P., et al.Diminished expression of CD40 ligand by activated neonatal T cells. J Clin Invest 1995; 95: 66–75CrossRefGoogle ScholarPubMed
Sleasman, J. W., Morimoto, C., Schlossman, S. F., Tedder, T. F.The role of functionally distinct helper T lymphocyte subpopulations in the induction of human B cell differentiation. Eur J Immunol 1990; 20: 1357–1366CrossRefGoogle ScholarPubMed
Buckley, R. H.Humoral immunodeficiency. Clin Immunol Immunopathol 1986; 40: 13–24CrossRefGoogle ScholarPubMed
Vetrie, D., Vorechovsky, I., Sideras, P., et al.The gene involved in X-linked agammaglobulinaemia is a member of the src family of protein-tyrosine kinases. Nature 1993; 361: 226–233CrossRefGoogle ScholarPubMed
Paul, M. E., Shearer, W. T. Approach to the evaluation of the immunodeficient patient. In Rich, R. R., Fleisher, T. A., Shearer, W. T., Kotzin, B. L., Schroeder, H. W., eds. Clinical Immunology: Principles and Practice, Vol. 1. London: Mosby, 2001: 33.1–33.11Google Scholar
Ochs, H. D., Smith, C. I.X-linked agammaglobulinemia. A clinical and molecular analysis. Medicine (Baltimore) 1996; 75: 287–299Google ScholarPubMed
Kanegane, H., Futatani, T., Wang, Y., et al.Clinical and mutational characteristics of X-linked agammaglobulinemia and its carrier identified by flow cytometric assessment combined with genetic analysis. J Allergy Clin Immunol 2001; 108: 1012–1020CrossRefGoogle ScholarPubMed
Linch, D. C., Beverley, P. C., Levinsky, R. J., Rodeck, C. H.Phenotypic analysis of fetal blood leucocytes: potential for prenatal diagnosis of immunodeficiency disorders. Prenat Diagn 1982; 2: 211–218CrossRefGoogle ScholarPubMed
Fuleihan, R. L.The hyper IgM syndrome. Curr Allergy Asthma Rep 2001; 1: 445–450CrossRefGoogle ScholarPubMed
Levy, J., Espanol-Boren, T., Thomas, C., et al.Clinical spectrum of X-linked hyper-IgM syndrome. J Pediatr 1997; 131: 47–54CrossRefGoogle ScholarPubMed
Callard, R. E., Armitage, R. J., Fanslow, W. C., Spriggs, M. K.CD40 ligand and its role in X-linked hyper-IgM syndrome. Immunol Today 1993; 14: 559–564CrossRefGoogle ScholarPubMed
Lane, P., Traunecker, A., Hubele, S., et al.Activated human T cells express a ligand for the human B cell-associated antigen CD40 which participates in T cell-dependent activation of B lymphocytes. Eur J Immunol 1992; 22: 2573–2578CrossRefGoogle Scholar
Noelle, R. J., Roy, M., Shepherd, D. M., et al.A 39-kDa protein on activated helper T cells binds CD40 and transduces the signal for cognate activation of B cells. Proc Natl Acad Sci USA 1992; 89: 6550–6554CrossRefGoogle ScholarPubMed
Spriggs, M. K., Fanslow, W. C., Armitage, R. J., Belmont, J.The biology of the human ligand for CD40. J Clin Immunol 1993; 13: 373–380CrossRefGoogle ScholarPubMed
Ochs, H. D., Hollenbaugh, D., Aruffo, A.The role of CD40L (gp39)/CD40 in T/B cell interaction and primary immunodeficiency. Semin Immunol 1994; 6: 337–341CrossRefGoogle Scholar
Padayachee, M., Feighery, C., Finn, A., et al.Mapping of the X-linked form of hyper-IgM syndrome (HIGM1) to Xq26 by close linkage to HPRT. Genomics 1992; 14: 551–553CrossRefGoogle ScholarPubMed
Schwaber, J., Rosen, F. S.X chromosome linked immunodeficiency. Immunodefic Rev 1990; 2: 233–251Google ScholarPubMed
Tiller, T. L. Jr, Buckley, R. H.Transient hypogammaglobulinemia of infancy: review of the literature, clinical and immunologic features of 11 new cases, and long-term follow-up. J Pediatr 1978; 92: 347–353CrossRefGoogle ScholarPubMed
McGeady, S. J.Transient hypogammaglobulinemia of infancy: need to reconsider name and definition. J Pediatr 1987; 110: 47–50CrossRefGoogle ScholarPubMed
Dressler, F., Peter, H. H., Muller, W., Rieger, C. H.Transient hypogammaglobulinemia of infancy: five new cases, review of the literature and redefinition. Acta Paediatr Scand 1989; 78: 767–774CrossRefGoogle ScholarPubMed
English, B. K., Schroeder, H. W., Wilson, C. B. Immaturity of the fetal and neonatal immune system. In Rich, R. R., Fleisher, T. A., Shearer, W. T., Kotzin, B. L., Schroeder, H. W., eds. Clinical Immunology: Principles and Practice, Vol. 1. London: Mosby, 2001: 40.1–40.10Google Scholar
Geha, R. S.Antibody deficiency syndromes and novel immunodeficiencies. Pediatr Infect Dis J 1988; 7: S57–S60CrossRefGoogle ScholarPubMed
Schroeder, H. W. Primary antibody deficiency. In: Rich, R. R., Fleisher, T. A., Shearer, W. T., Kotzin, B. L., Schroeder, H. W., ed. Clinical Immunology: Principles and Practice. St Louis: Mosby International, 2001Google Scholar
Buckley, R. H.Primary cellular immunodeficiencies. J Allergy Clin Immunol 2002; 109: 747–757CrossRefGoogle ScholarPubMed
Hong, R.The DiGeorge anomaly. Clin Rev Allergy Immunol 2001; 20: 43–60CrossRefGoogle ScholarPubMed
Cormier-Daire, V., Iserin, L., Theophile, D., et al.Upper limb malformations in DiGeorge syndrome. Am J Med Genet 1995; 56: 39–41CrossRefGoogle ScholarPubMed
Sullivan, K. E.DiGeorge syndrome/chromosome 22q11.2 deletion syndrome. Curr Allergy Asthma Rep 2001; 1: 438–444CrossRefGoogle ScholarPubMed
Junker, A. K., Driscoll, D. A.Humoral immunity in DiGeorge syndrome. J Pediatr 1995; 127: 231–237CrossRefGoogle ScholarPubMed
Jawad, A. F., McDonald-Mcginn, D. M., Zackai, E., Sullivan, K. E.Immunologic features of chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial syndrome). J Pediatr 2001; 139: 715–723CrossRefGoogle Scholar
Klein, C., Lisowska-Grospierre, B., LeDeist, F., Fischer, A., Griscelli, C.Major histocompatibility complex class II deficiency: clinical manifestations, immunologic features, and outcome. J Pediatr 1993; 123: 921–928CrossRefGoogle ScholarPubMed
Nagarajan, U. M., Louis-Plence, P., DeSandro, A., et al.RFX-B is the gene responsible for the most common cause of the bare lymphocyte syndrome, an MHC class II immunodeficiency. Immunity 1999; 10: 153–162CrossRefGoogle ScholarPubMed
Mofenson, L. M.Mother-child HIV-1 transmission: timing and determinants. Obstet Gynecol Clin North Am 1997; 24: 759–784CrossRefGoogle ScholarPubMed
Shearer, W. T., Quinn, T. C., LaRussa, P., et al.Viral load and disease progression in infants infected with human immunodeficiency virus type 1. Women and Infants Transmission Study Group. N Engl J Med 1997; 336: 1337–1342CrossRefGoogle ScholarPubMed
1993 revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults. MMWR Recomm Rep 1992; 41: 1–19
Ochs, H. D.The Wiskott-Aldrich syndrome. Clin Rev Allergy Immunol 2001; 20: 61–86CrossRefGoogle ScholarPubMed
Buckley, R. H.Primary immunodeficiency diseases due to defects in lymphocytes. N Engl J Med 2000; 343: 1313–1324CrossRefGoogle ScholarPubMed
International Union of Immunological Societies. Primary immunodeficiency diseases: report of an IUIS Scientific Committee. Clin Exp Immunol 1999; 118 (Suppl 1): 1–28CrossRef
Sullivan, K. E.Recent advances in our understanding of Wiskott–Aldrich syndrome. Curr Opin Hematol 1999; 6: 8–14CrossRefGoogle ScholarPubMed
Thrasher, A. J.WASp in immune-system organization and function. Nat Rev Immunol 2002; 2: 635–646CrossRefGoogle ScholarPubMed
Derry, J. M., Ochs, H. D., Francke, U.Isolation of a novel gene mutated in Wiskott–Aldrich syndrome. Cell 1994; 78: 635–644CrossRefGoogle ScholarPubMed
Saint Basile, G., Arveiler, B., Fraser, N. J., et al.Close linkage of hypervariable marker DXS255 to disease locus of Wiskott–Aldrich syndrome. Lancet 1989; 2: 1319–1321CrossRefGoogle ScholarPubMed
Finan, P. M., Soames, C. J., Wilson, L., et al.Identification of regions of the Wiskott–Aldrich syndrome protein responsible for association with selected Src homology 3 domains. J Biol Chem 1996; 271: 26291–26295CrossRefGoogle ScholarPubMed
Schwarz, K.WASPbase: a database of WAS- and XLT-causing mutations. Immunol Today 1996; 17: 496–502CrossRefGoogle ScholarPubMed
Schwartz, M., Bekassy, A., Donner, M., et al.Mutation spectrum in patients with Wiskott–Aldrich syndrome and X- linked thrombocytopenia: identification of twelve different mutations in the WASP gene. Thromb Haemost 1996; 75: 546–550Google Scholar
Schindelhauer, D., Weiss, M., Hellebrand, H., et al.Wiskott–Aldrich syndrome: no strict genotype-phenotype correlations but clustering of missense mutations in the amino-terminal part of the WASP gene product. Hum Genet 1996; 98: 68–76CrossRefGoogle ScholarPubMed
Ochs, H. D., Rosen, F. S. The Wiskott–Aldrich syndrome. In Ochs, H. D., Smith, C. I. E., Puck, J. M., eds. Primary Immunodeficiency Diseases: A Molecular and Genetic Approach. Oxford: Oxford University Press, 1999: 292–305Google Scholar
Fischer, A.Severe combined immunodeficiencies. Immunodefic Rev 1992; 3: 83–100Google ScholarPubMed
Buckley, R. H., Fischer, A. Bone marrow transplantation for primary immunodeficiency diseases. In Ochs, H. D., Smith, C. I. E., Puck, J. M., eds. Primary Immunodeficiency Diseases: A Molecular and Genetic Approach. Oxford: Oxford University Press, 1999: 459–475Google Scholar
Buckley, R. H.Advances in the understanding and treatment of human severe combined immunodeficiency. Immunol Res 2000; 22: 237–251CrossRefGoogle ScholarPubMed
Buckley, R. H., Schiff, S. E., Schiff, R. I., et al.Hematopoietic stem-cell transplantation for the treatment of severe combined immunodeficiency. N Engl J Med 1999; 340: 508–516CrossRefGoogle ScholarPubMed
Puck, J. M., Conley, M. E., Bailey, L. C.Refinement of linkage of human severe combined immunodeficiency (SCIDX1) to polymorphic markers in Xq13. Am J Hum Genet 1993; 53: 176–184Google ScholarPubMed
Puck, J. M., Deschenes, S. M., Porter, J. C., et al.The interleukin-2 receptor gamma chain maps to Xq13.1 and is mutated in X-linked severe combined immunodeficiency, SCIDX1. Hum Mol Genet 1993; 2: 1099–1104CrossRefGoogle ScholarPubMed
Vosshenrich, C. A., Di Santo, J. P.Cytokines: IL-21 joins the gamma(c)-dependent network?Curr Biol 2001; 11: R175–R177CrossRefGoogle ScholarPubMed
Noguchi, M., Yi, H., Rosenblatt, H. M., et al.Interleukin-2 receptor gamma chain mutation results in X-linked severe combined immunodeficiency in humans. Cell 1993; 73: 147–157CrossRefGoogle ScholarPubMed
Sleasman, J. W., Harville, T. O., White, G. B., et al.Arrested rearrangement of TCR V beta genes in thymocytes from children with X-linked severe combined immunodeficiency disease. J Immunol 1994; 153: 442–448Google ScholarPubMed
Elder, M. E., Lin, D., Clever, J., et al.Human severe combined immunodeficiency due to a defect in ZAP-70, a T cell tyrosine kinase. Science 1994; 264: 1596–1599CrossRefGoogle ScholarPubMed
Buckley, R. H., Schiff, R. I., Schiff, S. E., et al.Human severe combined immunodeficiency: genetic, phenotypic, and functional diversity in one hundred eight infants. J Pediatr 1997; 130: 378–387CrossRefGoogle ScholarPubMed
Hirschhorn, R. Immunodeficiency diseases due to deficiency of adenosine deaminase. In Ochs, H. D., Smith, C. I. E., Puck, J. M., eds. Primary Immunodeficiency Diseases: A Molecular and Genetic Approach. Oxford: Oxford University Press, 1999: 121–139Google Scholar
Hirschhorn, R.Adenosine deaminase deficiency. Immunodefic Rev 1990; 2: 175–198Google ScholarPubMed
Santagata, S., Villa, A., Sobacchi, C., Cortes, P., Vezzoni, P.The genetic and biochemical basis of Omenn syndrome. Immunol Rev 2000; 178: 64–74CrossRefGoogle ScholarPubMed
Villa, A., Santagata, S., Bozzi, F., Imberti, L., Notarangelo, L. D.Omenn syndrome: a disorder of Rag1 and Rag2 genes. J Clin Immunol 1999; 19: 87–97CrossRefGoogle ScholarPubMed
Rieux-Laucat, F., Bahadoran, P., Brousse, N., et al.Highly restricted human T cell repertoire in peripheral blood and tissue-infiltrating lymphocytes in Omenn's syndrome. J Clin Invest 1998; 102: 312–321CrossRefGoogle Scholar
Brooks, E. G., Filipovich, A. H., Padgett, J. W., Mamlock, R., Goldblum, R. M.T-cell receptor analysis in Omenn's syndrome: evidence for defects in gene rearrangement and assembly. Blood 1999; 93: 242–250Google Scholar
Magnuson, N. S., Perryman, L. E.Metabolic defects in severe combined immunodeficiency in man and animals. Comp Biochem Physiol B 1986; 83: 701–710CrossRefGoogle ScholarPubMed
Colten, H. R., Rosen, F. S.Complement deficiencies. Annu Rev Immunol 1992; 10: 809–834CrossRefGoogle ScholarPubMed
Frank, M. M.Complement deficiencies. Pediatr Clin North Am 2000; 47: 1339–1354CrossRefGoogle ScholarPubMed
Virella, G., Sleasman, J. W. Diagnosis of immunodeficiency diseases. In: Virella, G., ed. Medical Immunology, Vol. 1. New York: Marcel Dekker, 2001: 555–572Google Scholar
Puck, J. M.Molecular and genetic basis of X-linked immunodeficiency disorders. J Clin Immunol 1994; 14: 81–89CrossRefGoogle ScholarPubMed
Puck, J. M.Prenatal diagnosis and genetic analysis of X-linked immunodeficiency disorders. Pediatr Res 1993; 33: S29–S33, S33–S34CrossRefGoogle ScholarPubMed
Martin, N. L., Levy, J. A., Legg, H., et al.Detection of infection with human immunodeficiency virus (HIV) type 1 in infants by an anti-HIV immunoglobulin A assay using recombinant proteins. J Pediatr 1991; 118: 354–358CrossRefGoogle ScholarPubMed
McIntosh, K., Comeau, A. M., Wara, D., et al.The utility of IgA antibody to human immunodeficiency virus type 1 in early diagnosis of vertically transmitted infection. National Institute of Allergy and Infectious Diseases and National Institute of Child Health and Human Development Women and Infants Transmission Study Group. Arch Pediatr Adolesc Med 1996; 150: 598–602CrossRefGoogle ScholarPubMed
Buckley, R. H.Breakthroughs in the understanding and therapy of primary immunodeficiency. Pediatr Clin North Am 1994; 41: 665–690CrossRefGoogle ScholarPubMed
Ohlsson, A., Lacy, J. B. Intravenous immunoglobulin for preventing infection in preterm and/or low-birth-weight infants. Cochrane Database Syst Rev 2001; 2
Skull, S., Kemp, A.Treatment of hypogammaglobulinaemia with intravenous immunoglobulin, 1973–93. Arch Dis Child 1996; 74:527–530CrossRefGoogle ScholarPubMed
Ohlsson, A., Lacy, J. B. Intravenous immunoglobulin for suspected or subsequently proven infection in neonates. Cochrane Database Syst Rev 2001; 2
Christensen, R. D., Brown, M. S., Hall, D. C., Lassiter, H. A., Hill, H. R.Effect on neutrophil kinetics and serum opsonic capacity of intravenous administration of immune globulin to neonates with clinical signs of early-onset sepsis. J Pediatr 1991; 118: 606–614CrossRefGoogle ScholarPubMed
Weisman, L. E., Stoll, B. J., Kueser, T. J., et al.Intravenous immune globulin therapy for early-onset sepsis in premature neonates. J Pediatr 1992; 121: 434–443CrossRefGoogle ScholarPubMed
Shroeder, H. W. Primary antibody deficiency. In: Rich, R. R., Fleisher, T. A., Shearer, W. T., Kotzin, B. L., Schroeder, H. W., eds. Clinical Immunology: Principles and Practice. St Louis: Mosby International, 2001Google Scholar
Committee on Infectious Diseases, American Academy of Pediatrics. Red Book: Report of the Committee on Infectious Diseases, Vol. 1. Elk Grove: American Academy of Pediatrics, 2000
Sacher, R. A., King, J. C.Intravenous gamma-globulin in pregnancy: a review. Obstet Gynecol Surv 1989; 44: 25–34CrossRefGoogle ScholarPubMed
Madsen, D. L., Catanzarite, V. A., Varela-Gittings, F.Common variable hypogammaglobulinemia in pregnancy: treatment with high-dose immunoglobulin infusions. Am J Hematol 1986; 21: 327–329CrossRefGoogle ScholarPubMed
Barros, M. D., Porto, M. H., Leser, P. G., Grumach, A. S., Carneiro-Sampaio, M. M.Study of colostrum of a patient with selective IgA deficiency. Allergol Immunopathol (Madr) 1985; 13: 331–334Google ScholarPubMed
Rosen, F.Severe combined immunodeficiency: a pediatric emergency. J Pediatr 1997; 130: 345–346Google ScholarPubMed
Haynes, B. F., Hale, L. P.The human thymus: a chimeric organ comprised of central and peripheral lymphoid components. Immunol Res 1998; 18: 175–192CrossRefGoogle ScholarPubMed
Webber, S. A., Hatchwell, E., Barber, J. C., et al.Importance of microdeletions of chromosomal region 22q11 as a cause of selected malformations of the ventricular outflow tracts and aortic arch: a three-year prospective study. J Pediatr 1996; 129: 26–32CrossRefGoogle ScholarPubMed
Gong, W., Emanuel, B. S., Collins, J., et al.A transcription map of the DiGeorge and velo-cardio-facial syndrome minimal critical region on 22q11. Hum Mol Genet 1996; 5: 789–800CrossRefGoogle ScholarPubMed
Driscoll, D. A., Sullivan, K. E. DiGeorge syndrome: a chromosome 22q11.2 deletion syndrome. In Ochs, H. D., Smith, C. I. E., Puck, J. M., ed. Primary Immunodeficiency Diseases: A Molecular and Genetic Approach. Oxford: Oxford University Press, 1999: 198–208Google Scholar
Lipson, A., Fagan, K., Colley, A., et al.Velo-cardio-facial and partial DiGeorge phenotype in a child with interstitial deletion at 10p13: implications for cytogenetics and molecular biology. Am J Med Genet 1996; 65: 304–3083.0.CO;2-Y>CrossRefGoogle Scholar
Schuffenhauer, S., Seidel, H., Oechsler, H., et al.DiGeorge syndrome and partial monosomy 10p: case report and review. Ann Genet 1995; 38: 162–167Google ScholarPubMed
Daw, S. C., Taylor, C., Kraman, M., et al.A common region of 10p deleted in DiGeorge and velocardiofacial syndromes. Nat Genet 1996; 13: 458–460CrossRefGoogle ScholarPubMed
Stephan, J. L., Vlekova, V., Deist, F., et al.Severe combined immunodeficiency: a retrospective single-center study of clinical presentation and outcome in 117 patients. J Pediatr 1993; 123: 564–572CrossRefGoogle ScholarPubMed
Uhr, J. W.Delayed hypersensitivity. Physiol Rev 1966; 46: 359–419CrossRefGoogle ScholarPubMed
Harville, T. O., Adams, D. M., Howard, T. A., Ware, R. E.Oligoclonal expansion of CD45RO+ T lymphocytes in Omenn syndrome. J Clin Immunol 1997; 17: 322–332CrossRefGoogle ScholarPubMed
Fischer, A.Primary T-cell immunodeficiencies. Curr Opin Immunol 1993; 5: 569–578CrossRefGoogle ScholarPubMed
Hershfield, M. S.Adenosine deaminase deficiency: clinical expression, molecular basis, and therapy. Semin Hematol 1998; 35: 291–298Google ScholarPubMed
Parolini, O., Ressmann, G., Haas, O. A., et al.X-linked Wiskott–Aldrich syndrome in a girl. N Engl J Med 1998; 338: 291–295CrossRefGoogle Scholar
Hershfield, M. S., Buckley, R. H., Greenberg, M. L., et al.Treatment of adenosine deaminase deficiency with polyethylene glycol-modified adenosine deaminase. N Engl J Med 1987; 316: 589–596CrossRefGoogle ScholarPubMed
Hershfield, M. S.PEG-ADA replacement therapy for adenosine deaminase deficiency: an update after 8.5 years. Clin Immunol Immunopathol 1995; 76: S228–S232CrossRefGoogle ScholarPubMed
Hershfield, M. S.PEG-ADA: an alternative to haploidentical bone marrow transplantation and an adjunct to gene therapy for adenosine deaminase deficiency. Hum Mutat 1995; 5: 107–112CrossRefGoogle ScholarPubMed
Cavazzana-Calvo, M., Hacein-Bey, S., Saint Basile, G., et al.Gene therapy of human severe combined immunodeficiency (SCID)-X1 disease. Science 2000; 288: 669–672CrossRefGoogle ScholarPubMed
Hacein-Bey-Abina, S., Deist, F., Carlier, F., et al.Sustained correction of X-linked severe combined immunodeficiency by ex vivo gene therapy. N Engl J Med 2002; 346: 1185–1193CrossRefGoogle ScholarPubMed
Recommendations for use of antiretroviral drugs in pregnant HIV-1-infected women for maternal health and interventions to reduce perinatal HIV-1 transmission in the United States. Morb Mortal Wkly Rep 2002: 1–46
Connor, E. M., Sperling, R. S., Gelber, R., et al.Reduction of maternal-infant transmission of human immunodeficiency virus type 1 with zidovudine treatment. Pediatric AIDS Clinical Trials Group Protocol 076 Study Group. N Engl J Med 1994; 331: 1173–1180CrossRefGoogle ScholarPubMed
Centers for Disease Control and Prevention. Revised classification system for human immunodeficiency virus infection in children less than 13 years of age. Morbid Mortal Wkly Rep 1994; 43: 1–12
Sleasman, J. W., Kahler, D.Antiretroviral Therapy in Children: HIV/AIDS Primary Care Guide 2002. Gainesville, FL: University of Florida Press, 2002Google Scholar
Sleasman, J. W.The impact of antiretroviral therapy on the treatment and prevention of pediatric HIV infection. Current Treatment Options in Infectious Diseases 1999; 2: 109–113Google Scholar
Scott, G. B., SJ. Pediatric HIV Infection: HIV/AIDS Primary Care Guide. Gainesville, FL: University of Florida Press, 1999
Ross, S. C., Densen, P.Complement deficiency states and infection: epidemiology, pathogenesis and consequences of neisserial and other infections in an immune deficiency. Medicine (Baltimore) 1984; 63: 243–273CrossRefGoogle Scholar
Miller, M. E., Koblenzer, P. J.Leiner's disease and deficiency of C5. J Pediatr 1972; 80: 879–880CrossRefGoogle ScholarPubMed

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