61
1. Ryan AK, G.J., Wilson DI et al., Spectrum of clinical features assocated with interstitial chromosome 22q11 deletions. J Med Genet, 1997(34): p. 798-804. 2. AM, D., Congenital absence of the thymus and its immunological consequences:
concurrance with congenital hypothyroidism. Birth Defects, 1968(4): p. 116-121. 3. C. Cancrini, B.M., A. Plebani, P.Rossi Sindrome da delezione 22q11.2, in I
quaderni dell'immunodeficienza. 2010.
4. L. Bartolozzi, E.B., G.R. BURGIO, A. Ceci, F. Chiarelli, S. Cucchiara, F. De Luca, M. Duse, R. Iorio, E. Leva, A. Masseri, F. Mosca, P. Nucci, A. Pession, W. Rigamonti, A.G.Ugazio, N. Zadra, Pediatria, principi e pratica clinica. Quarta ed. 2013.
5. Botto LD, M.K., Fernhoff PM et al, A population-based study of the 22q11.2 deletion: phenotype, incidence, and contribution to major birth defects in the population. Pediatrics, 2003. 112: p. 101-107.
6. Jerome LA, P.V., DiGeorge syndrome phenotype in mice mutant fot the T box gene, Tbx1. Nat Genet, 2010(27): p. 286-291.
7. Carlson C, S.H., Pandita R, Goldberg R, McKie J, Wadey R, Pantanjali SR, Weissman SM, Anyane-Yeboa K, Warburton D, Scrambler P, Shprintzen R, Kucherlapati R, ,Morrow BE, Molecular Definition of 22q11 deletions in 151 velo-cardio-facial syndrome patients. Am J Hum Genet, 1997(61): p. 620-629.
8. Edelman L, P.R., Morrow BE, Low-copy repeats mediate the common 3-Mb deletion in patients with velo-cardio-facial syndrome. Am J Hum Genet, 1999(64): p. 1076-1086.
62
9. Meechan DW, M.T., GOpalakrishna D, Wu Y, LaMantia AS, When half is not enough: gene expression and dosage in the 22q11.2 delection syndrome. Gene expr, 2007(13): p. 299-310.
10. Schinze M, I.S., Deconstructing DiGeorge syndrome. Nat Genet, 2001(27): p. 238-240.
11. Sullivan KE, M.-M.D., Driscoll DA, Emanuel BS, Zackai EH, Jawad AF, Longitudinal analysis of lymphocyte function and numbers in the first year of life in chromosome 22q11.2 delection syndrome. Clin Diagn Lab immunol, 1996(6): p. 906-911.
12. Sullivan KE, J.A., Randall P et al. , Lack of correlation between impaired T cell production, immunodeficiency, and other phenotypic features in chromosome 22q11.2 deletion syndrome. Clinic immunol immunopathol, 1998(86): p. 141-146. 13. Oskardottir S., P.C., Eriksson BO., Fasth A., Presenting phenotype in 100 children
with the 22q11 deletion syndrome. Eur J Pediatr, 2005(164): p. 146-153.
14. Carotti A, D.M., Piacentini G et al. , Cardiac defects and results of cardiac surgery in 22q11.2 deletion syndrome. . Dev Disabil Res Rev, 2008(14).
15. Cotrupi M.C., G.R., Ferraù V., Cuppari C., Briuglia S., Rigoli L., Damiano CS., La Sindrome DiGeorge: peculiarità cliniche e genetiche. Rivista di Immunologia e Allergologia Pediatrica, 2008: p. 37-48.
16. G. Igli Baroncelli, F.V., A. Bartoli, G. Saggese, Ipocalcemia: un sintomo dalle tante "facies". . Medico e bambino pagine elettroniche, 2008: p. 11.
17. Conley ME., B.J., Mancer JF, Tenckhoff L., The spectrum of the DiGeorge Syndrome. J Pediatr, 1979(94): p. 883-890.
63
18. Brown JJ, D.V., Browning MJ, Swift PJF, Patient resport with a review of endocrine autoimmunity associated with 22q11.2 delection. J Pediatr Endocrinol Metab, 2004(17): p. 1575-1579.
19. Jawad AF, M.-M.D., Zackai E, Sullivan KE, Immunologic fetures of chromosome 22q11.2 deletion syndrome. J Pediatr, 2001(139): p. 715-723.
20. KE, S., The clinical, immunological, and molecular spectrum of chromosome 22q11.2 deletion syndrome. Curr Opin Allergy Clin Immunol, 2004(4): p. 505-512. 21. Junker AK, D.D., Humoral immunity in DiGeorge syndrome. J Pediatr, 1995(127):
p. 231-237.
22. Gennery AR, B.D., O'Sullivan JJ, et al, Antibody deficiency and autoimmunity in 22q11.2 deletion syndrome. Arch Dis Child, 2002(86): p. 442-425.
23. McDonald-McGinn DM, K.R., Goldmuntz E, et al, The Philadelphia story: the 22q11.2 deletion: report on 250 patients. Genet Couns, 1999(10): p. 11-24.
24. A. McLean-Tooke, G.P.S., A.R. Gennery, Immunodeficiency and Autoiimunity in 22q11.2 Deletion Syndrome. The Authors, 2007(66): p. 1-7.
25. Finocchi A, D.C.S., Romiti ML, Capponi C, Rossi P, Carsetti R, Cancrini C, Humoral immune responses and CD27+ B cells in children with DiGeorge Syndrome. The Authors, 2006(17): p. 382-388.
26. Perez E, S.K., Chromosome 22q11.2 deletion syndrome. Curr Opin Pediatr, 2002(14): p. 678-683.
27. C. Cancrini, P.P., MC Digilio, A. Soresina, S. Martino, R. Rondelli, R. Consolini, EM Ruga, F.Cardinale, A. Finocchi, ML Romiti BSc PhD, Baldassarre Martire
64
MD, R. Bacchetta MD, V. Albano MD et al., Clinical features of a large cohort of 22q.11 del 22 syndrome: an Italian multicenter study.
28. Lewandowski KE, S.V., Berry PM, Kwapil TR, Schizophrenic-like neurocognitive deficits in children and adolescents with 22q11 deletion syndrome. Am J Med Genet B Neuropsychiatr Genet, 2007(144): p. 27-36.
29. Eliez S, B.C., Menon V et al. , Functional brain imaging study of mathematical reasoning abilities in velocardiofacial syndrome (del22q11.2). Genet Med, 2001(3): p. 49-55.
30. Carey AH, K.D., Halford S, Wadey R, Wilson D, Gooship J, et al, Molecular genetic study of the frequency of monosomy 22q11.2 in DiGeorge syndrome. Am J Hum Genet, 1992(51): p. 964-970.
31. Yamagashi H, S.D., Unravelling the genetic and development mysteries of 22q11 deletion syndrome. Trends Mol Med, 2003(9): p. 383-389.
32. Taddei I, M.M., Huynh T, Lindsay EA, Genetic factors are major determinans of phenotype variability in a mouse model of the DiGeorge/del22q11 syndromes. Proc Natl Acad Sci USA, 2001(98): p. 11428-11431.
33. Coppinger J, M.-M.D., Zackai E et al. , Identification of familial and de novo microduplication of 22q11.21-q11.23 distal to the 22q11.21 microdeletion syndrome region. Hum Mol Genet, 2009(18): p. 1377-1383.
34. Driscoll DA, S.J., Sellinger B et al. 7, Prevalence of 22q11 microdeletions in DiGeorge and velocardiofacial syndromes: implications for genetic counselling and prenatal diagnosis. J Med Genet, 1993(30): p. 813-817.
65
35. De la Chapelle A, H.K., Koivisto M, Aula P, A deletion in chromosome 22 can cause DiGeorge syndrome. Hum Genet, 1981(57): p. 253-256.
36. Driscoll DA, B.M., Emanuel BS, A genetic etiology for DiGeorge syndrome: consistent deletions and microdeletions of 22q11. Am J Hum Genet, 1992(50): p. 924-933.
37. Driscoll DA, S.N., Budarf ML, McDonald-McGinn DM, Zackai EH, Goldberg RB, et al, Deletions and microdeletions of 22q11.2 in velo-cardio-facial syndrome. Am J Med Genet, 1992(44): p. 261-268.
38. Hou JW, W.J., Tsai WY, Chou CC, Wang TR, CATCH 22: deletion of locus 22q11 in velocardiofacial syndrome, DiGeorge anomaly, and nonsyndromic conotruncal defects. J Formos Med Assoc, 1997(96): p. 419-423.
39. Lammer EJ, O.J., The DiGeorge anomaly as a development field defect. Am J Hum Genet Suppl, 1986(2): p. 113-127.
40. Rope AF, C.D., Saal HM, Hopkin RJ, DiGeorge anomaly in the absence of chromosome 22q11.2 deletion. J Pediatr, 2009(155): p. 560-565.
41. Abbas AK, L.A., Le basi dell'immunologia 2006.
42. Von Andrian UH, M.T., Homing and cellular traffic in lymph nodes. Nature reviews Immunology, 2003(3): p. 269-279.
43. Underhill DM, O.A., Phagocytosis of microbes: complexity in action. 2003(20): p. 825-852.
44. Lieberman N, M.O., The role of NK cells in innate immunity. Advance in experimental Medicine and Biology, 2000(479): p. 137-145.
66
45. Bulet PR, S.R., Menin L, Anti-microbial peptides: from invertebrates to vertebrates. Immunological Reviews, 2004(198): p. 169-189.
46. T, G., Defensis: anti-microbial peptides of innate immunity Nature reviews Immunology, 2003(3): p. 710-720.
47. Scluns KS, L.L., Cytokine control of memory T-cell developmente and survival. Nature reviews Immunology, 2003(3): p. 269-279.
48. Ackerman AL, C.P., Cellular mechanism governing cross-presentation of exogenous antigens. Nature Immunology, 2004(5): p. 678-684.
49. Davis SJ, I.S., Evans EJ, Fugger L, Bakker TR, Vander Merwe PA, The nature of molecular recognition by T cells. Nature Immunology, 2003(4): p. 217-224.
50. Herwadkar A, G.A., Moran AS, Haeney MR, Arkwright PD, Association between hypoparathyroidism and defective T cell immunity in 22q11.2 deletion syndrome. J Clin Pathol, 2010.
51. Clark EA, L.J., How B and T cells talk to each other. Nature, 1994(367): p. 425-428.
52. PJ, B., MHC restrictionin three dimensions: a view of T cell receptor/ligand interactions. Cell, 1997(89): p. 167-170.
53. Germain RN, S.I., The dynamics of T cell receptor signaling: complex orchestration and the key roles of tempo and cooperation. Annual Reviw of Immunology, (19): p. 467-522.
54. Hollander G, G.J., Zuklys S, Iwanami N, Liu C. Takahama Y, Cellular and molecular events during early thymus development. Immunol Rev, 2006(209): p. 28-46.
67
55. Barthlott T, K.M., Krenger W, Hollander GA, A shorter primer on early molecular and cellular events in thymus organogenesis and replacement. Swiss Med Wkly, 2006(136): p. 356-369.
56. Le Lievre CS, L.D.n., Mesenchymal derivatives of the neural crest: analysis of chimeric quail and chick embryos. J Embryol Exp Morphol, 1975(34): p. 125-154. 57. Haynes BF, H.C., Early human T cell development: analysis of the human thymus
at the time of initial entry of hematopoietic stem cells into the fetal thymic microenvironment. J Exp Med, 1995(181): p. 1445-1458.
58. CM, R., Studies of patients' thymi aid in the discovery and characterization of immunodeficiency in humans. Immunol Rev, 2006(203): p. 143-155.
59. Blackburn CC, M.N., Developing a new paradigm for thymus organogenesis. Nat Rev Immunol, 2004(4): p. 278-289.
60. Starr TK, J.S., Hogquist KA, Positive and negative selection of T cells. Annu Rev Immunol, 2003(21): p. 139-176.
61. Akiyama T, S.Y., Yanai H, Qin J, Ohshima D, Maruyama Y, Asaumi Y, Kitazawa J, Takahama Y, Inoue J, The tumor necrosis factor family receptors RANK and CD40 cooperatively establish the thymic medullary microenviroment and self-tollerance. Immunity, 2008(29): p. 423-437.
62. Zuklys S, B.G., Agarwal A, Fasler-Kan E, Palmer E, Hollander GA, Normal thymic architecture and negative selection are associated with Aire expression, the gene defective in the autoimmune-polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). J Immunol, 2000(165): p. 1976-1983.
68
63. Watanabe N, W.Y., Lee HK, Ito T, Cao W, Liu YJ, Hassal's corpuscles intruct dendritic cells to induce CD4+CD25+ regulatory T cells in human thymus. Nature, 2005(436): p. 1181-1185.
64. APECED, C.F.-G., An autoimmune disease, APECED, caused by mutations in a novel gene featuring two PHD-type zinc-finger domains. Nat Genet, 1999(17): p. 399-403.
65. Poliani PL, F.F., Ravanini M, Gennery AR, Villa A, Roifman CM, Notarangelo LD, Early defects in human T-cell development severely affect distribuition and maturation of thymic stromal cells: possible implications fot the patho-physiology of Omenn syndrome. Blood, 2009(114): p. 105-108.
66. Bennett CL, C.J., Ramsdell F, Brunkow ME, Ferguson PJ, Whitesell L, Kelly TE, Saulsbury FT, Chance PF, Ochs HD, The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3. Nat Genet, 2001(27): p. 20-21.
67. Poliani PL, V.W., Facchetti F, Thymus microenviroment in human primary immunodeficiency diseases. Curr Opin Allergy Clin Immunol, 2009(9): p. 489-495. 68. Fu YX, C.D., Development and maturation of secondary lymphoid tissues Annual
Reviw of Immunology, 1999(17): p. 399-433.
69. Piliero LM, S.A., Donald-McGinn DM, Zackai EH, Sullivan KE, T-cell homeostasis in humans with thymic hypoplasia due to chormosome 22q11 deletion syndrome. Blood, 2004(103): p. 1020-1025.
70. Bastian J, L.S., Vogler L et al., Prediction of persistent immunodeficiency in the DiGeorge anomaly. J Pediatr, 1989(115): p. 391-396.
69
71. R, H., The DiGeorge anomaly. Immunodefic Rev, 1991(3): p. 1-14.
72. H. Xu, F.C., A. Baldini Timed mutation and cell-fate mapping reveal reitered roles of TBX1 during embryogenesis and a crucial function during segmentation of the pharyngeal system via regulation of endoderm expansion. Development, 2005(132): p. 4387-4395.
73. Bockman DE, K.M., Dependence of thymus development on derivates of the neural crest. Science, 1984(223): p. 498-500.
74. Gennary, A., Immunological aspects of 22q11.2 deletion syndrome. Cell Mol Life Sci, 2011.
75. KE, S., The clinical, immunological, and molecular spectrum of chromosome 22q11.2 deletion syndrome and DiGeorge syndrome. Curr Opin Allergy Clin Immunol, 2004(27): p. 238-240.
76. Chinen J, R.H., Smith EO, Sherer WT, Noroski LM, Long term assessment of T-cell populations in DiGeorge syndrome. J Allergy Clin Immunol, 2003(111): p. 573-579.
77. Markert ML, B.A., Hale LP et al. , Transplantation of thymus tissue in complete DiGeorge syndrome. N Engl J Med, 1999(341): p. 1180-1189.
78. Shah SS, L.S., Ruchelli E, Kazahaya K, Mahboubi S, Retropharyngeal aberrant thymus. Pediatrics, 2001(108).
79. Sediva A, B.J., Zachova R et al, Early development of immunity in DiGeorge syndrome. Med Sci Monit, 2005(11): p. 182-187.
70
80. Pierdominici M, M.F., Caprini E, et al, Biased T-cell receptor repertoires in patients with chromosome 22q11.2 deletion syndrome. Clin Exp Immunol, 2003(132): p. 323-331.
81. Markert ML, A.M., Li J et al, Complete DiGeorge syndrome: development of rash, lymphadenopathy, and oligoclonal T cells in 5 cases, J Allergy Clin Immunol, 2004(113): p. 734-741.
82. Puliafito P, D.C.S., Romiti ML, Martino S, Rondelli R, Putti C, Soresina A, Digilio MC, Cocchi G, Martire B, Marchetti V, Montin D, Azzarri C, Pignata C, Pietrogrande MC, Carsetti R, Aiuti A, Plebani A, Rossi P, Cancrini C, Immunological alteration in a large cohort of 22q11.2 deletion syndrome patients. Network for Primary Immunodeficiencies.
83. Eberle P, B.C., Junge S, Dougoud S, Buchel EV, Riegel M, Schinzel A, Seger R, Gungor T, Persistent low thymic activity and non-cardiac mortality in children with chromosome 22q11.2 microdeletion and partial DiGeorge syndrome. Clin Exp Immunol, 2009(155): p. 189-198.
84. Smith CA, D.D., Emanuel BS, et al, Increased prevalence of immunoglobulin a deficiency in patients with the chromosome 22q11.2 deletion syndrome. Clin Diagn Lab immunol, 1998(5): p. 415-417.
85. Kornfeld SJ, Z.B., Christodoulou CS, et al, DiGeorge anomaly: a comparative study of the clinical and immunologic characteristicd of patients positive and negative by fluorescence in situ hybridization. J Allergy Clin Immunol, 2000(105): p. 983-987.
71
86. Schubert MS, M.R., Selective polysaccharide antibody deficiency in familial 22q11.2 syndrome. Ann Allergy, 1992(69): p. 231-238.
87. Patel K, J.A., Kobrynski L, Gathman B, Davis O, Sullivan KE, Immunoglobulin Deficiencies: the B lymphocyte side of DiGeorge syndrome. J Pediatr, 2012. 161(5). 88. Shubert MS, M.R., Selective polysaccharide antibody deficiency in familial
DiGeorge syndrome. Ann Allergy, 1992(69): p. 231-238.
89. Kung SJ, G.K., Stephan MJ, Fairchock MP, McGeady SJ, Selective IgM deficiency and 22q11.2 deletion syndrome. Ann Allergy Asthma Immunol, 2007(99): p. 87-92.
90. Vos Q, L.A., Wu ZQ, Snapper CM, Mond JJ, B-cell activation by T-cell-independent type 2 antigens as an integral part of the humoral immune response to pathogenic microorganism. Immunol Rev, (176): p. 154-170.
91. Kroon FP, V.D.J., Ravensbergen E, Nibbering PH, Van Furth R, Antobodies against pneumococcal polysaccharides after vaccination in HIV-infected individuals: 5-years follow-up of antobody concentrations. Vaccine, 1999(18): p. 524.
92. Mayumi M, K.H., Suehiro Y, et al, 22q11.2 syndrome with hypogammaglobulinaemia: a patient with excess suppressor T cell activity treted with fetal thymus transplantation. Eur J Pediatr, 1989(149): p. 512-522.
93. Kanaya Y, O.S., Ikeda K, Furuno K, Ohno T, Takada H, Kinukawa N, Hara T, Maturational alterations of peripheral T cell subsets and cytokine gene expression in 22q11.2 deletion syndrome. Clin Exp Immunol, 2006(144): p. 85-93.
72
94. Legitimo A, C.G., Ottaviano V, Consolini R, Macchia P, Petrini M, Measurement of thymic outoput by multicolor flow cytometry. Cytometry, 2010. Part A 77A(184): p. 144-202.
95. Orsini G, F.A., Legitimo A, Adinolfi B, Romanini A, Consolini R, Zoledronic acid modulates maturation of human monocyte-derived dendritic cells. Exp Biol Med, 2011.
96. Orsini G, L.A., Failli A, Massei F, Biver P, Consolini R, Distribution of human circulating dendritic cells throughout the life.
97. Boyman O, L.S., Krieg C, Sprent J, Homeostatic proliferation and survival of naive and memory T cells. Eur J Pediatr, 2009(39): p. 2088-2094.
98. Boyman O, P.J., Surh CD, Sprent J, Citokinines and T-cell homeostasis. Curr Opin Allergy Clin Immunol, 2007(19): p. 320-326.
99. Kieper WC, J.S., Homeostatic expansion and phenotype conversion of naive T cells in response to self/MHC ligands. Proc Natl Acad Sci USA, 1999(96): p. 13306-13311.
100. SC, J., Maintaining the norm: T-cell homeostasis. Nat Rev Immunol, 2002(2): p. 547-556.
101. Prlic M, B.B., Khoruts A, Zell T, Jameson SC, Homeostatic expansion occurs independently of costimulatory signals. J Immunol, 2001(167): p. 5664-5668. 102. Tan JT, E.B., Kieper WC, LeRoy E, Sprent J, Surh CD, Interleukin (IL)-15 and
IL-7 jointly regulate homeostatic proliferation of memory phenotype CD8+ cells but are not require for memory phenotype CD4+ cells. J Exp Med, 2002(195): p. 1523-1532.
73
103. Tan Jt, D.E., LeRoy E, Murray R, Sprent J, Weinberg KI, Surh CD, IL-7 is critical for homeostatic proliferation and survival of naive T cells. Proc Natl Acad Sci USA, 2001(98): p. 8732-8737.
104. Sprent J, C.J., Boyman O, Surh CD, T cell homeostasis. Immunol Cell Biol, 2008(86): p. 312-319.
105. Milner JD, W.J., Keane-Myers, Paul WE, Lymphopenic mice reconstituted with limited repertoire T cells develop severe, multiorgan, Th2-associated inflammatory disease. Proc Natl Acad Sci USA, 2007(104): p. 576-581.
106. King C, I.A., Koelsch K, Sarvetnick N, Homeostatic expansion of T cells during immune insufficiency generates autoimmunity. Cell, 2004(117): p. 265-277.
107. Min B, F.G., Meier-Schellersheim M, Paul WE, Spontaneous proliferation, a response of naive CD4 T cells determined by the diversity of the memory cell repertoire. Proc Natl Acad Sci USA, 2004(101): p. 3874-3879.
108. Surh CD, S.J., Homeostasis of naive and memory T cells. Immunity, 2008(29): p. 848-862.
109. Jang E, K.H., Cho SH, Paik DJ, Kim JM, Lee SK, Youn J, Prevention of spontaneous arthritis by inhibiting homeostatic expansion oh autoreactive CD4+ T cells in the K/BxN mouse model. Arthritis Rheum, 2006(54): p. 492-498.
110. Marleau AM, S.N., T cell homeostasis in tolerance and immunity. J Leukoc Biol, 2005(78): p. 575-584.
111. Tison BE, N.S., Abramson SL, Hanson IC, Paul ME, Seeborg FO, Shearer WT, Perez MD, Noroski LM, Chinen J, Autoimmunity in a cohort of 130 pediatric
74
patients with partial DiGeorge syndrome. J Allergy Clin Immunol, 2011. 128: p. 1115-1116.
112. Shurman SH, C.F., Autoimmunty in Wiskott-Aldrich syndrome Curr Opin Rheumatol, 2003(15): p. 446-453.
113. Zemble R, L.P.E., McDonald K, McDonald-McGinn D, Zackai E, Sullivan K, Secondary immunoloigc consequences in chromosome 22q11.2 deletion syndrome. Clin Immunol, 2010(136): p. 409-418.
114. Dejaco C, D.C., Grubeck-Loebenstein B, Schirmer M, Imbalance of regulatory T cells in human autoimmune diseases. Immunology, 2006(117): p. 289-300.
115. Le Bras S, G.R., IPEX and the role of FOXP3 in the development and function of human Tregs. J Clin Invest, 2006(116): p. 1473-1475.
116. Asano M, T.M., Sakaguchi N, Sakaguchi S, Autoimmune disease as a consequence of development abnormality of a T cell subpopulation. J Exp Med, 1996(184): p. 387-396.
117. Cavadini P, V.W., Facchetti F et al, AIRE deficiency in thymus of 2 patients with Omenn syndrome J Clin Invest, 2005(115): p. 728-732.
118. Gleeson PA, T.B., Van Driel IR, Organ specific autoimmunity induced by lymphopenia. Immunol Rev, 1996(149): p. 97-125.
119. Mackall CL, H.F., Gress RE, Restoration of T cell homeostasis after lymphocyte depletion. Semin Immunol, 1997(9): p. 339-346.
120. Cox AL, T.S., Jones JL et al, Lymphocyte homeostasis following therapeutic lymphocyte depletion in multiple sclerosis. Eur J Immunol, 2005(35): p. 3332-3342.
