Autoimmune disease in primary immunodeficiency: At the Crossroads of Anti-Infective Immunity and Self-Tolerance

Immunology and Allergy Clinics of North America

Volumn 35, Issue 4, 2015, Pages 731-752

  Saifi, Maryam ^a   Wysocki, Christian A ^a  

^a UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

Author keywords

Apoptosis; Autoimmunity; Common variable immunodeficiency; Primary immunodeficiency; Regulatory T cell; Tolerance

Indexed keywords

ACTIVATION INDUCED CYTIDINE DEAMINASE; B CELL ACTIVATING FACTOR; B LYMPHOCYTE RECEPTOR; BRUTON TYROSINE KINASE; CD40 LIGAND; TRANSMEMBRANE ACTIVATOR AND CAML INTERACTOR;

APOPTOSIS; ARTICLE; AUTOIMMUNE DISEASE; AUTOIMMUNE HEPATITIS; AUTOIMMUNE LYMPHOPROLIFERATIVE SYNDROME; AUTOIMMUNE POLYENDOCRINOPATHY CANDIDIASIS ECTODERMAL DYSTROPHY; COMMON VARIABLE IMMUNODEFICIENCY; COMPLEMENT DEFICIENCY; DIGEORGE SYNDROME; ENTEROPATHY; GENE MUTATION; GENETIC PREDISPOSITION; GRANULOMATOUS INTERSTITIAL LUNG DISEASE; HEMOPHAGOCYTIC SYNDROME; HUMAN; HYPER IGM SYNDROME; IMMUNE DEFICIENCY; IMMUNOLOGICAL TOLERANCE; IPEX SYNDROME; NODULAR REGENERATIVE HYPERPLASIA; NONHUMAN; OMENN SYNDROME; PENETRANCE; PRIORITY JOURNAL; REGULATORY T LYMPHOCYTE; RHEUMATOID ARTHRITIS; SEVERE COMBINED IMMUNODEFICIENCY; WISKOTT ALDRICH SYNDROME; X LINKED AGAMMAGLOBULINEMIA; AUTOIMMUNE DISEASES; AUTOIMMUNITY; B LYMPHOCYTE; COMPLICATION; GENETICS; IMMUNOLOGIC DEFICIENCY SYNDROMES; IMMUNOLOGY; INFLAMMATION; METABOLISM; T LYMPHOCYTE;

AUTOIMMUNE DISEASES; AUTOIMMUNITY; B-LYMPHOCYTES; COMMON VARIABLE IMMUNODEFICIENCY; HUMANS; IMMUNE TOLERANCE; IMMUNOLOGIC DEFICIENCY SYNDROMES; INFLAMMATION; T-LYMPHOCYTES;

EID: 84955185358     PISSN: 08898561     EISSN: 15578607     Source Type: Journal    
DOI: 10.1016/j.iac.2015.07.007     Document Type: Review

References (147)

1. Ozen S, Bilginer Y. A clinical guide to autoinflammatory diseases: familial Mediterranean fever and next-of-kin. Nat Rev Rheumatol 2014;10(3):135-47.
2. Klein L, Kyewski B, Allen PM, et al. Positive and negative selection of the Tcell repertoire: what thymocytes see (and don't see). Nat Rev Immunol 2014;14(6):377-91.
3. Anderson MS, Venanzi ES, Klein L, et al. Projection of an immunological self shadow within the thymus by the AIRE protein. Science 2002;298(5597): 1395-401.
4. Zumer K, Saksela K, Peterlin BM. The mechanism of tissue-restricted antigen gene expression by AIRE. J Immunol 2013;190(6):2479-82.
5. Nagamine K, Peterson P, Scott HS, et al. Positional cloning of the APECED gene. Nat Genet 1997;17(4):393-8.
6. De Martino L, Capalbo D, Improda N, et al. APECED: a paradigm of complex interactions between genetic background and susceptibility factors. Front Immunol 2013;4:331.
7. Puel A, Doffinger R, Natividad A, et al. Autoantibodies against IL-17A, IL-17F, and IL-22 in patients with chronic mucocutaneous candidiasis and autoimmune polyendocrine syndrome type I. J Exp Med 2010;207(2):291-7.
8. Su MA, Anderson MS. AIRE: an update. Curr Opin Immunol 2004;16(6):746-52.
9. Zuklys S, Balciunaite G, Agarwal A, et al. 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(4):1976-83.
10. Cavadini P, Vermi W, Facchetti F, et al. AIRE deficiency in thymus of 2 patients with Omenn syndrome. J Clin Invest 2005;115(3):728-32.
11. Capalbo D, Giardino G, Martino LD, et al. Genetic basis of altered central tolerance and autoimmune diseases: a lesson from AIRE mutations. Int Rev Immunol 2012;31(5):344-62.
12. Jawad AF, McDonald-Mcginn DM, Zackai E, et al. Immunologic features of chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial syndrome). J Pediatr 2001;139(5):715-23.
13. Gennery AR, Barge D, O'Sullivan JJ, et al. Antibody deficiency and autoimmunity in 22q11.2 deletion syndrome. Arch Dis Child 2002;86(6):422-5.
14. Ferrando-Martinez S, Lorente R, Gurbindo D, et al. Low thymic output, peripheral homeostasis deregulation, and hastened regulatory T cells differentiation in children with 22q11.2 deletion syndrome. J Pediatr 2014;164(4):882-9.
15. Siggs OM, Miosge LA, Yates AL, et al. Opposing functions of the T cell receptor kinase ZAP-70 in immunity and tolerance differentially titrate in response to nucleotide substitutions. Immunity 2007;27(6):912-26.
16. Kim KD, Srikanth S, Yee MK, et al. ORAI1 deficiency impairs activated T cell death and enhances T cell survival. J Immunol 2011;187(7):3620-30.
17. McCarl CA, Picard C, Khalil S, et al. ORAI1 deficiency and lack of storeoperated Ca21 entry cause immunodeficiency, myopathy, and ectodermal dysplasia. J Allergy Clin Immunol 2009;124(6):1311-8.e17.
18. Picard C, McCarl CA, Papolos A, et al. STIM1 mutation associated with a syndrome of immunodeficiency and autoimmunity. N Engl J Med 2009;360(19):1971-80.
19. Oh-Hora M, Yamashita M, Hogan PG, et al. Dual functions for the endoplasmic reticulum calcium sensors STIM1 and STIM2 in T cell activation and tolerance. Nat Immunol 2008;9(4):432-43.
20. Lenardo M, Chan KM, Hornung F, et al. Mature T lymphocyte apoptosis-immune regulation in a dynamic and unpredictable antigenic environment. Annu Rev Immunol 1999;17:221-53.
21. Watanabe-Fukunaga R, Brannan CI, Copeland NG, et al. Lymphoproliferation disorder in mice explained by defects in Fas antigen that mediates apoptosis. Nature 1992;356(6367):314-7.
22. Wilson NS, Dixit V, Ashkenazi A. Death receptor signal transducers: nodes of coordination in immune signaling networks. Nat Immunol 2009;10(4):348-55.
23. Oliveira JB. The expanding spectrum of the autoimmune lymphoproliferative syndromes. Curr Opin Pediatr 2013;25(6):722-9.
24. Del-Rey M, Ruiz-Contreras J, Bosque A, et al. A homozygous Fas ligand gene mutation in a patient causes a new type of autoimmune lymphoproliferative syndrome. Blood 2006;108(4):1306-12.
25. Wang J, Zheng L, Lobito A, et al. Inherited human Caspase 10 mutations underlie defective lymphocyte and dendritic cell apoptosis in autoimmune lymphoproliferative syndrome type II. Cell 1999;98(1):47-58.
26. Chun HJ, Zheng L, Ahmad M, et al. Pleiotropic defects in lymphocyte activation caused by caspase-8 mutations lead to human immunodeficiency. Nature 2002; 419(6905):395-9.
27. Bolze A, Byun M, McDonald D, et al. Whole-exome-sequencing-based discovery of human FADD deficiency. Am J Hum Genet 2010;87(6):873-81.
28. Kuehn HS, Niemela JE, Rangel-Santos A, et al. Loss-of-function of the protein kinase C delta (PKCdelta) causes a B-cell lymphoproliferative syndrome in humans. Blood 2013;121(16):3117-25.
29. Oliveira JB, Bidere N, Niemela JE, et al. NRAS mutation causes a human autoimmune lymphoproliferative syndrome. Proc Natl Acad Sci U S A 2007;104(21): 8953-8.
30. Niemela JE, Lu L, Fleisher TA, et al. Somatic KRAS mutations associated with a human nonmalignant syndrome of autoimmunity and abnormal leukocyte homeostasis. Blood 2011;117(10):2883-6.
31. Takagi M, Shinoda K, Piao J, et al. Autoimmune lymphoproliferative syndromelike disease with somatic KRAS mutation. Blood 2011;117(10):2887-90.
32. Arason GJ, Jorgensen GH, Ludviksson BR. Primary immunodeficiency and autoimmunity: lessons from human diseases. Scand J Immunol 2010;71(5):317-28.
33. Pickering MC, Botto M, Taylor PR, et al. Systemic lupus erythematosus, complement deficiency, and apoptosis. Adv Immunol 2000;76:227-324.
34. Arason GJ, Geirsson AJ, Kolka R, et al. Deficiency of complement-dependent prevention of immune precipitation in systemic sclerosis. Ann Rheum Dis 2002;61(3):257-60.
35. Arason GJ, Steinsson K, Kolka R, et al. Patients with systemic lupus erythematosus are deficient in complement-dependent prevention of immune precipitation. Rheumatology 2004;43(6):783-9.
36. Bussone G, Mouthon L. Autoimmune manifestations in primary immune deficiencies. Autoimmun Rev 2009;8(4):332-6.
37. Etzioni A. Immune deficiency and autoimmunity. Autoimmun Rev 2003;2(6): 364-9.
38. Kang EM, Marciano BE, DeRavin S, et al. Chronic granulomatous disease: overview and hematopoietic stem cell transplantation. J Allergy Clin Immunol 2011; 127(6):1319-26 [quiz: 1327-8].
39. Kelkka T, Kienhofer D, Hoffmann M, et al. Reactive oxygen species deficiency induces autoimmunity with type 1 interferon signature. Antioxid Redox Signal 2014;21(16):2231-45.
40. Toro-Dominguez D, Carmona-Saez P, Alarcon-Riquelme ME. Shared signatures between rheumatoid arthritis, systemic lupus erythematosus and Sjogren's syndrome uncovered through gene expression meta-analysis. Arthritis Res Ther 2014;16(6):489.
41. Kraaij MD, Savage ND, van der Kooij SW, et al. Induction of regulatory T cells by macrophages is dependent on production of reactive oxygen species. Proc Natl Acad Sci U S A 2010;107(41):17686-91.
42. Sakaguchi S, Sakaguchi N, Asano M, et al. Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J Immunol 1995;155(3):1151-64.
43. Fontenot JD, Gavin MA, Rudensky AY. Foxp3 programs the development and function of CD41CD251 regulatory T cells. Nat Immunol 2003;4(4):330-6.
44. Bennett CL, Christie J, Ramsdell F, et al. The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3. Nat Genet 2001;27(1):20-1.
45. Wildin RS, Ramsdell F, Peake J, et al. X-linked neonatal diabetes mellitus, enteropathy and endocrinopathy syndrome is the human equivalent of mouse scurfy. Nat Genet 2001;27(1):18-20.
46. Chatila TA, Blaeser F, Ho N, et al. JM2, encoding a fork head-related protein, is mutated in X-linked autoimmunity-allergic dysregulation syndrome. J Clin Invest 2000;106(12):R75-81.
47. Zhang L, Zhao Y. The regulation of Foxp3 expression in regulatory CD4(1) CD25(1)T cells: multiple pathways on the road. J Cell Physiol 2007;211(3): 590-7.
48. Caudy AA, Reddy ST, Chatila T, et al. CD25 deficiency causes an immune dysregulation, polyendocrinopathy, enteropathy, X-linked-like syndrome, and defective IL-10 expression from CD4 lymphocytes. J Allergy Clin Immunol 2007;119(2):482-7.
49. Cohen AC, Nadeau KC, Tu W, et al. Cutting edge: decreased accumulation and regulatory function of CD41 CD25(high) T cells in human STAT5b deficiency. J Immunol 2006;177(5):2770-4.
50. Lohr NJ, Molleston JP, Strauss KA, et al. Human ITCH E3 ubiquitin ligase deficiency causes syndromic multisystem autoimmune disease. Am J Hum Genet 2010;86(3):447-53.
51. Venuprasad K, Huang H, Harada Y, et al. The E3 ubiquitin ligase Itch regulates expression of transcription factor Foxp3 and airway inflammation by enhancing the function of transcription factor TIEG1. Nat Immunol 2008;9(3):245-53.
52. Sansom DM, Walker LS. The role of CD28 and cytotoxic T-lymphocyte antigen-4 (CTLA-4) in regulatory T-cell biology. Immunol Rev 2006;212:131-48.
53. Waterhouse P, Penninger JM, Timms E, et al. Lymphoproliferative disorders with early lethality in mice deficient in Ctla-4. Science 1995;270(5238):985-8.
54. Tivol EA, Borriello F, Schweitzer AN, et al. Loss of CTLA-4 leads to massive lymphoproliferation and fatal multiorgan tissue destruction, revealing a critical negative regulatory role of CTLA-4. Immunity 1995;3(5):541-7.
55. Schubert D, Bode C, Kenefeck R, et al. Autosomal dominant immune dysregulation syndrome in humans with CTLA4 mutations. Nat Med 2014;20(12): 1410-6.
56. Kuehn HS, Ouyang W, Lo B, et al. Immune dysregulation in human subjects with heterozygous germline mutations in CTLA4. Science 2014;345(6204):1623-7.
57. Charbonnier LM, Janssen E, Chou J, et al. Regulatory T-cell deficiency and immune dysregulation, polyendocrinopathy, enteropathy, X-linked-like disorder caused by loss-of-function mutations in LRBA. J Allergy Clin Immunol 2015; 135(1):217-27.e219.
58. Lopez-Herrera G, Tampella G, Pan-Hammarstrom Q, et al. Deleterious mutations in LRBA are associated with a syndrome of immune deficiency and autoimmunity. Am J Hum Genet 2012;90(6):986-1001.
59. Serwas NK, Kansu A, Santos-Valente E, et al. Atypical manifestation of LRBA deficiency with predominant IBD-like phenotype. Inflamm Bowel Dis 2015; 21(1):40-7.
60. Alangari A, Alsultan A, Adly N, et al. LPS-responsive beige-like anchor (LRBA) gene mutation in a family with inflammatory bowel disease and combined immunodeficiency. J Allergy Clin Immunol 2012;130(2):481-8.e2.
61. Fevang B, Yndestad A, Sandberg WJ, et al. Low numbers of regulatory T cells in common variable immunodeficiency: association with chronic inflammation in vivo. Clin Exp Immunol 2007;147(3):521-5.
62. Yu GP, Chiang D, Song SJ, et al. Regulatory T cell dysfunction in subjects with common variable immunodeficiency complicated by autoimmune disease. Clin Immunol 2009;131(2):240-53.
63. Arumugakani G, Wood PM, Carter CR. Frequency of Treg cells is reduced in CVID patients with autoimmunity and splenomegaly and is associated with expanded CD21lo B lymphocytes. J Clin Immunol 2010;30(2):292-300.
64. Genre J, Errante PR, Kokron CM, et al. Reduced frequency of CD4(1) CD25(HIGH)FOXP3(1) cells and diminished FOXP3 expression in patients with common variable immunodeficiency: a link to autoimmunity? Clin Immunol 2009;132(2):215-21.
65. Maillard MH, Cotta-de-Almeida V, Takeshima F, et al. The Wiskott-Aldrich syndrome protein is required for the function of CD4(1)CD25(1)Foxp3(1) regulatory T cells. J Exp Med 2007;204(2):381-91.
66. Milner JD, Vogel TP, Forbes L, et al. Early-onset lymphoproliferation and autoimmunity caused by germline STAT3 gain-of-function mutations. Blood 2015; 125(4):591-9.
67. Janssen E, Morbach H, Ullas S, et al. Dedicator of cytokinesis 8-deficient patients have a breakdown in peripheral B-cell tolerance and defective regulatory T cells. J Allergy Clin Immunol 2014;134(6):1365-74.
68. Sullivan KE, McDonald-McGinn D, Zackai EH. CD4(1) CD25(1) T-cell production in healthy humans and in patients with thymic hypoplasia. Clin Diagn Lab Immunol 2002;9(5):1129-31.
69. Goodnow CC, Sprent J, Fazekas de St Groth B, et al. Cellular and genetic mechanisms of self tolerance and autoimmunity. Nature 2005;435(7042):590-7.
70. Ng YS, Wardemann H, Chelnis J, et al. Bruton's tyrosine kinase is essential for human B cell tolerance. J Exp Med 2004;200(7):927-34.
71. Chew GY, Sinha U, Gatenby PA, et al. Autoimmunity in primary antibody deficiency is associated with protein tyrosine phosphatase nonreceptor type 22 (PTPN22). J Allergy Clin Immunol 2013;131(4):1130-5, 1135.e1.
72. Isnardi I, Ng YS, Srdanovic I, et al. IRAK-4-and MyD88-dependent pathways are essential for the removal of developing autoreactive B cells in humans. Immunity 2008;29(5):746-57.
73. Castigli E, Wilson SA, Garibyan L, et al. TACI is mutant in common variable immunodeficiency and IgA deficiency. Nat Genet 2005;37(8):829-34.
74. Salzer U, Chapel HM, Webster AD, et al. Mutations in TNFRSF13B encoding TACI are associated with common variable immunodeficiency in humans. Nat Genet 2005;37(8):820-8.
75. Lee JJ, Ozcan E, Rauter I, et al. Transmembrane activator and calciummodulator and cyclophilin ligand interactor mutations in common variable immunodeficiency. Curr Opin Allergy Clin Immunol 2008;8(6):520-6.
76. Romberg N, Chamberlain N, Saadoun D, et al. CVID-associated TACI mutations affect autoreactive B cell selection and activation. J Clin Invest 2013;123(10): 4283-93.
77. Notarangelo LD, Lanzi G, Peron S, et al. Defects of class-switch recombination. J Allergy Clin Immunol 2006;117(4):855-64.
78. Quartier P, Bustamante J, Sanal O, et al. Clinical, immunologic and genetic analysis of 29 patients with autosomal recessive hyper-IgM syndrome due to Activation-Induced Cytidine Deaminase deficiency. Clin Immunol 2004;110(1): 22-9.
79. Revy P, Muto T, Levy Y, et al. Activation-induced cytidine deaminase (AID) deficiency causes the autosomal recessive form of the Hyper-IgM syndrome (HIGM2). Cell 2000;102(5):565-75.
80. Meyers G, Ng YS, Bannock JM, et al. Activation-induced cytidine deaminase (AID) is required for B-cell tolerance in humans. Proc Natl Acad Sci U S A 2011;108(28):11554-9.
81. Jesus AA, Duarte AJ, Oliveira JB. Autoimmunity in hyper-IgM syndrome. J Clin Immunol 2008;28(Suppl 1):S62-6.
82. Herve M, Isnardi I, Ng YS, et al. CD40 ligand and MHC class II expression are essential for human peripheral B cell tolerance. J Exp Med 2007;204(7): 1583-93.
83. Kumanogoh A, Wang X, Lee I, et al. Increased T cell autoreactivity in the absence of CD40-CD40 ligand interactions: a role of CD40 in regulatory T cell development. J Immunol 2001;166(1):353-60.
84. Stohl W, Xu D, Kim KS, et al. BAFF overexpression and accelerated glomerular disease in mice with an incomplete genetic predisposition to systemic lupus erythematosus. Arthritis Rheum 2005;52(7):2080-91.
85. Thien M, Phan TG, Gardam S, et al. Excess BAFF rescues self-reactive B cells from peripheral deletion and allows them to enter forbidden follicular and marginal zone niches. Immunity 2004;20(6):785-98.
86. Lesley R, Xu Y, Kalled SL, et al. Reduced competitiveness of autoantigenengaged B cells due to increased dependence on BAFF. Immunity 2004; 20(4):441-53.
87. Knight AK, Radigan L, Marron T, et al. High serum levels of BAFF, APRIL, and TACI in common variable immunodeficiency. Clin Immunol 2007;124(2):182-9.
88. Mackay F, Sierro F, Grey ST, et al. The BAFF/APRIL system: an important player in systemic rheumatic diseases. Curr Dir Autoimmun 2005;8:243-65.
89. Foerster C, Voelxen N, Rakhmanov M, et al. B cell receptor-mediated calcium signaling is impaired in B lymphocytes of type Ia patients with common variable immunodeficiency. J Immunol 2010;184(12):7305-13.
90. Rakhmanov M, Keller B, Gutenberger S, et al. Circulating CD21low B cells in common variable immunodeficiency resemble tissue homing, innate-like B cells. Proc Natl Acad Sci U S A 2009;106(32):13451-6.
91. Isnardi I, Ng YS, Menard L, et al. Complement receptor 2/CD21-human naive B cells contain mostly autoreactive unresponsive clones. Blood 2010;115(24): 5026-36.
92. Wehr C, Kivioja T, Schmitt C, et al. The EUROclass trial: defining subgroups in common variable immunodeficiency. Blood 2008;111(1):77-85.
93. Chandrakasan S, Filipovich AH. Hemophagocytic lymphohistiocytosis: advances in pathophysiology, diagnosis, and treatment. J Pediatr 2013;163(5): 1253-9.
94. Terrell CE, Jordan MB. Perforin deficiency impairs a critical immunoregulatory loop involving murine CD8(1) T cells and dendritic cells. Blood 2013;121(26): 5184-91.
95. Jessen B, Kogl T, Sepulveda FE, et al. Graded defects in cytotoxicity determine severity of hemophagocytic lymphohistiocytosis in humans and mice. Front Immunol 2013;4:448.
96. Henter JI, Elinder G, Soder O, et al. Hypercytokinemia in familial hemophagocytic lymphohistiocytosis. Blood 1991;78(11):2918-22.
97. Henter JI, Horne A, Arico M, et al. HLH-2004: diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer 2007; 48(2):124-31.
98. Parvaneh N, Filipovich AH, Borkhardt A. Primary immunodeficiencies predisposed to Epstein-Barr virus-driven haematological diseases. Br J Haematol 2013;162(5):573-86.
99. Cunningham-Rundles C, Bodian C. Common variable immunodeficiency: clinical and immunological features of 248 patients. Clin Immunol 1999;92(1): 34-48.
100. Resnick ES, Moshier EL, Godbold JH, et al. Morbidity and mortality in common variable immune deficiency over 4 decades. Blood 2012;119(7):1650-7.
101. Chapel H, Lucas M, Lee M, et al. Common variable immunodeficiency disorders: division into distinct clinical phenotypes. Blood 2008;112(2): 277-86.
102. Bates CA, Ellison MC, Lynch DA, et al. Granulomatous-lymphocytic lung disease shortens survival in common variable immunodeficiency. J Allergy Clin Immunol 2004;114(2):415-21.
103. Lee AH, Levinson AI, Schumacher HR Jr. Hypogammaglobulinemia and rheumatic disease. Semin Arthritis Rheum 1993;22(4):252-64.
104. Swierkot J, Lewandowicz-Uszynska A, Chlebicki A, et al. Rheumatoid arthritis in a patient with common variable immunodeficiency: difficulty in diagnosis and therapy. Clin Rheumatol 2006;25(1):92-4.
105. Resnick ES, Cunningham-Rundles C. The many faces of the clinical picture of common variable immune deficiency. Curr Opin Allergy Clin Immunol 2012; 12(6):595-601.
106. Jin R, Kaneko H, Suzuki H, et al. Age-related changes in BAFF and APRIL profiles and upregulation of BAFF and APRIL expression in patients with primary antibody deficiency. Int J Mol Med 2008;21(2):233-8.
107. Wehr C, Eibel H, Masilamani M, et al. A new CD21low B cell population in the peripheral blood of patients with SLE. Clin Immunol 2004;113(2):161-71.
108. Park J, Munagala I, Xu H, et al. Interferon signature in the blood in inflammatory common variable immune deficiency. PLoS One 2013;8(9):e74893.
109. Gathmann B, Mahlaoui N, CEREDIH, et al. Clinical picture and treatment of 2212 patients with common variable immunodeficiency. J Allergy Clin Immunol 2014; 134(1):116-26.
110. Luzi G, Zullo A, Iebba F, et al. Duodenal pathology and clinical-immunological implications in common variable immunodeficiency patients. Am J Gastroenterol 2003;98(1):118-21.
111. Malamut G, Verkarre V, Suarez F, et al. The enteropathy associated with common variable immunodeficiency: the delineated frontiers with celiac disease. Am J Gastroenterol 2010;105(10):2262-75.
112. Teahon K, Webster AD, Price AB, et al. Studies on the enteropathy associated with primary hypogammaglobulinaemia. Gut 1994;35(9):1244-9.
113. Biagi F, Bianchi PI, Zilli A, et al. The significance of duodenal mucosal atrophy in patients with common variable immunodeficiency: a clinical and histopathologic study. Am J Clin Pathol 2012;138(2):185-9.
114. VenhoffN, Emmerich F, Neagu M, et al. The role of HLA DQ2 and DQ8 in dissecting celiac-like disease in common variable immunodeficiency. J Clin Immunol 2013;33(5):909-16.
115. Shulzhenko N, Morgun A, Hsiao W, et al. Crosstalk between B lymphocytes, microbiota and the intestinal epithelium governs immunity versus metabolism in the gut. Nat Med 2011;17(12):1585-93.
116. Mannon PJ, Fuss IJ, Dill S, et al. Excess IL-12 but not IL-23 accompanies the inflammatory bowel disease associated with common variable immunodeficiency. Gastroenterology 2006;131(3):748-56.
117. Lo B, Zhang K, Lu W, et al. Patients with LRBA deficiency show CTLA4 loss and immune dysregulation responsive to abatacept therapy. Science 2015; 359(6246):436-40.
118. Orange JS, Glessner JT, Resnick E, et al. Genome-wide association identifies diverse causes of common variable immunodeficiency. J Allergy Clin Immunol 2011;127(6):1360-7.e6.
119. Shi XZ, Sarna SK. Gene therapy of Cav1.2 channel with VIP and VIP receptor agonists and antagonists: a novel approach to designing promotility and antimotility agents. Am J Physiol Gastrointest Liver Physiol 2008;295(1):G187-96.
120. Maglione PJ, Ko HM, Beasley MB, et al. Tertiary lymphoid neogenesis is a component of pulmonary lymphoid hyperplasia in patients with common variable immunodeficiency. J Allergy Clin Immunol 2014;133(2):535-42.
121. Randall TD. Bronchus-associated lymphoid tissue (BALT) structure and function. Adv Immunol 2010;107:187-241.
122. Baris S, Schulze I, Ozen A, et al. Clinical heterogeneity of immunodysregulation, polyendocrinopathy, enteropathy, X-linked: pulmonary involvement as a nonclassical disease manifestation. J Clin Immunol 2014;34(6):601-6.
123. Saunders BM, Britton WJ. Life and death in the granuloma: immunopathology of tuberculosis. Immunol Cell Biol 2007;85(2):103-11.
124. Mullighan CG, Fanning GC, Chapel HM, et al. TNF and lymphotoxin-alpha polymorphisms associated with common variable immunodeficiency: role in the pathogenesis of granulomatous disease. J Immunol 1997;159(12): 6236-41.
125. Wheat WH, Cool CD, Morimoto Y, et al. Possible role of human herpesvirus 8 in the lymphoproliferative disorders in common variable immunodeficiency. J Exp Med 2005;202(4):479-84.
126. Prasse A, Kayser G, Warnatz K. Common variable immunodeficiencyassociated granulomatous and interstitial lung disease. Curr Opin Pulm Med 2013;19(5):503-9.
127. Fuss IJ, Friend J, Yang Z, et al. Nodular regenerative hyperplasia in common variable immunodeficiency. J Clin Immunol 2013;33(4):748-58.
128. Ward C, Lucas M, Piris J, et al. Abnormal liver function in common variable immunodeficiency disorders due to nodular regenerative hyperplasia. Clin Exp Immunol 2008;153(3):331-7.
129. Hartleb M, Gutkowski K, Milkiewicz P. Nodular regenerative hyperplasia: evolving concepts on underdiagnosed cause of portal hypertension. World J Gastroenterol 2011;17(11):1400-9.
130. Malamut G, Ziol M, Suarez F, et al. Nodular regenerative hyperplasia: the main liver disease in patients with primary hypogammaglobulinemia and hepatic abnormalities. J Hepatol 2008;48(1):74-82.
131. Wanless IR. Micronodular transformation (nodular regenerative hyperplasia) of the liver: a report of 64 cases among 2, 500 autopsies and a new classification of benign hepatocellular nodules. Hepatology 1990;11(5):787-97.
132. Nakanuma Y. Nodular regenerative hyperplasia of the liver: retrospective survey in autopsy series. J Clin Gastroenterol 1990;12(4):460-5.
133. Reshamwala PA, Kleiner DE, Heller T. Nodular regenerative hyperplasia: not all nodules are created equal. Hepatology 2006;44(1):7-14.
134. Ziol M, Poirel H, Kountchou GN, et al. Intrasinusoidal cytotoxic CD81 T cells in nodular regenerative hyperplasia of the liver. Hum Pathol 2004;35(10):1241-51.
135. Kiyuna A, Sunagawa T, Hokama A, et al. Nodular regenerative hyperplasia of the liver and Castleman's disease: potential role of interleukin-6. Dig Dis Sci 2005; 50(2):314-6.
136. Klein R, Goller S, Bianchi L. Nodular regenerative hyperplasia (NRH) of the liver-a manifestation of 'organ-specific antiphospholipid syndrome'? Immunobiology 2003;207(1):51-7.
137. Barzaghi F, Passerini L, Bacchetta R. Immune dysregulation, polyendocrinopathy, enteropathy, x-linked syndrome: a paradigm of immunodeficiency with autoimmunity. Front Immunol 2012;3:211.
138. Kluger N, Ranki A, Krohn K. APECED: is this a model for failure of T cell and B cell tolerance? Front Immunol 2012;3:232.
139. Tison BE, Nicholas SK, Abramson SL, et al. Autoimmunity in a cohort of 130 pediatric patients with partial DiGeorge syndrome. J Allergy Clin Immunol 2011; 128(5):1115-7.e1-3.
140. McLean-Tooke A, Barge D, Spickett GP, et al. Immunologic defects in 22q11.2 deletion syndrome. J Allergy Clin Immunol 2008;122(2):362-7, 367.e1-4.
141. Diehl L, Den Boer AT, van der Voort EI, et al. The role of CD40 in peripheral T cell tolerance and immunity. J Mol Med (Berlin, Germany) 2000;78(7):363-71.
142. Imai K, Slupphaug G, Lee WI, et al. Human uracil-DNA glycosylase deficiency associated with profoundly impaired immunoglobulin class-switch recombination. Nat Immunol 2003;4(10):1023-8.
143. Hanson EP, Monaco-Shawver L, Solt LA, et al. Hypomorphic nuclear factorkappaB essential modulator mutation database and reconstitution system identifies phenotypic and immunologic diversity. J Allergy Clin Immunol 2008;122(6): 1169-77.e16.
144. Yoshioka T, Nishikomori R, Hara J, et al. Autosomal dominant anhidrotic ectodermal dysplasia with immunodeficiency caused by a novel NFKBIA mutation, p. Ser36Tyr, presents with mild ectodermal dysplasia and non-infectious systemic inflammation. J Clin Immunol 2013;33(7):1165-74.
145. Hernandez-Trujillo VP, Scalchunes C, Cunningham-Rundles C, et al. Autoimmunity and inflammation in X-linked agammaglobulinemia. J Clin Immunol 2014; 34(6):627-32.
146. Cleland SY, Siegel RM. Wiskott-Aldrich syndrome at the nexus of autoimmune and primary immunodeficiency diseases. FEBS Lett 2011;585(23):3710-4.
147. Abbott JK, Gelfand EW. Common Variable Immunodeficiency: Diagnosis, Management, and Treatment. Immunol Allergy Clin North Am 2015, in press.