Skip to main content

Advertisement

SpringerLink
Log in

Inflammatory bowel disease: is it a primary immunodeficiency?

  • Multi-author review
  • Published:
Cellular and Molecular Life Sciences Aims and scope Submit manuscript

Abstract

Inflammatory bowel diseases (IBD) such as ulcerative colitis and Crohn’s disease are chronic and relapsing conditions, characterized by abdominal pain, diarrhea, bleeding and malabsorption. IBD has been considered a hyperinflammatory state due to disturbed interactions between the immune system and the commensal bacterial flora of the gut. However, there is evidence that Crohn’s disease might be the consequence of a reduced release of pro-inflammatory cytokines and an impaired acute inflammatory response, thereby suggesting that IBD might be an immunodeficiency rather than an excessive inflammatory reaction. This theory has been supported by observations in patients with primary immunodeficiencies such as the Wiskott–Aldrich syndrome and IPEX (immunodysregulation, polyendocrinopathy, enteropathy, X-linked syndrome). In contrary, defects in the anti-inflammatory down-regulation of the immune response as they are seen in patients with Mendelian defects in the IL10 signaling pathway support the hyper-inflammatory theory. In this review, we describe and discuss primary immunodeficiencies associated with IBD and show that the bowel is a highly sensitive indicator of dysregulations, making IBD a model disease to study and identify key regulators required to balance the human mucosal immune system.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Podolsky DK (2002) Inflammatory bowel disease. N Engl J Med 347:417–429

    PubMed  CAS  Google Scholar 

  2. Baumgart DC, Carding SR (2007) Inflammatory bowel disease: cause and immunobiology. Lancet 369:1627–1640

    PubMed  CAS  Google Scholar 

  3. Romano C, Famiani A, Gallizzi R et al (2008) Indeterminate colitis: a distinctive clinical pattern of inflammatory bowel disease in children. Pediatrics 122:e1278–e1281

    PubMed  Google Scholar 

  4. Xavier RJ, Podolsky DK (2007) Unravelling the pathogenesis of inflammatory bowel disease. Nature 448:427–434

    PubMed  CAS  Google Scholar 

  5. Carter MJ, Lobo AJ (2004) Travis SP; IBD Section, British Society of Gastroenterology. Guidelines for the management of inflammatory bowel disease in adults. Gut 53(Suppl 5):V1–V16

    PubMed  Google Scholar 

  6. Engel MA, Neurath MF (2010) New pathophysiological insights and modern treatment of IBD. J Gastroenterol 45:571–583

    PubMed  CAS  Google Scholar 

  7. Spencer SD, Di Marco F, Hooley J et al (1998) The orphan receptor CRF2–4 is an essential subunit of the interleukin 10 receptor. J Exp Med 187:571–578

    PubMed  CAS  Google Scholar 

  8. Mizoguchi A, Mizoguchi E (2008) Inflammatory bowel disease, past, present and future: lessons from animal models. J Gastroenterol 43:1–17

    PubMed  Google Scholar 

  9. Elson CO, Cong Y, McCracken VJ, Dimmitt RA, Lorenz RG, Weaver CT (2005) Experimental models of inflammatory bowel disease reveal innate, adaptive, and regulatory mechanisms of host dialogue with the microbiota. Immunol Rev 206:260–276

    PubMed  Google Scholar 

  10. Onderdonk AB, Hermos JA, Bartlett JG (1977) The role of the intestinal microflora in experimental colitis. Am J Clin Nutr 30:1819–1825

    PubMed  CAS  Google Scholar 

  11. Barnes M, Powrie F (2009) Regulatory T cells reinforce intestinal homeostasis. Immunity 31:401–411

    PubMed  CAS  Google Scholar 

  12. Artis D (2008) Epithelial-cell recognition of commensal bacteria and maintenance of immune homeostasis in the gut. Nat Rev Immunol 8:411–420

    PubMed  CAS  Google Scholar 

  13. Boden EK, Snapper SB (2008) Regulatory T cells in inflammatory bowel disease. Curr Opin Gastroenterol 24:733–741

    PubMed  Google Scholar 

  14. Fontenot JD, Gavin MA, Rudensky AY (2003) Foxp3 programs the development and function of CD4+ CD25+ regulatory T cells. Nat Immunol 4:330–336

    PubMed  CAS  Google Scholar 

  15. Li MO, Wan YY, Flavell RA (2007) T cell-produced transforming growth factor-beta1 controls T cell tolerance and regulates Th1- and Th17-cell differentiation. Immunity 26:579–591

    PubMed  CAS  Google Scholar 

  16. Rubtsov YP, Rasmussen JP, Chi EY, Fontenot J, Castelli L, Ye X, Treuting P, Siewe L, Roers A, Henderson WR Jr, Muller W, Rudensky AY (2008) Regulatory T cell-derived interleukin-10 limits inflammation at environmental interfaces. Immunity 28:546–558

    PubMed  CAS  Google Scholar 

  17. Cho JH (2008) The genetics and immunopathogenesis of inflammatory bowel disease. Nat Rev Immunol 8:458–466

    PubMed  CAS  Google Scholar 

  18. Van Limbergen J, Wilson DC, Satsangi J (2009) The genetics of Crohn’s disease. Annu Rev Genomics Hum Genet 10:89–116

    PubMed  Google Scholar 

  19. Barrett JC, Hansoul S, Nicolae DL et al (2008) Genome-wide association defines more than 30 distinct susceptibility loci for Crohn’s disease. Nat Genet 40:955–962

    PubMed  CAS  Google Scholar 

  20. Hampe J, Franke A, Rosenstiel P et al (2007) A genome-wide association scan of nonsynonymous SNPs identifies a susceptibility variant for Crohn disease in ATG16L1. Nat Genet 39:207–211

    PubMed  CAS  Google Scholar 

  21. Parkes M, Barrett JC, Prescott NJ et al (2007) Sequence variants in the autophagy gene IRGM and multiple other replicating loci contribute to Crohn’s disease susceptibility. Nat Genet 39:830–832

    PubMed  CAS  Google Scholar 

  22. Cadwell K, Liu JY, Brown SL et al (2008) A key role for autophagy and the autophagy gene Atg16l1 in mouse and human intestinal Paneth cells. Nature 456:259–263

    PubMed  CAS  Google Scholar 

  23. Hugot JP, Chamaillard M, Zouali H et al (2001) Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn’s disease. Nature 411:599–603

    PubMed  CAS  Google Scholar 

  24. Economou M, Trikalinos TA, Loizou KT et al (2004) Differential effects of NOD2 variants on Crohn’s disease risk and phenotype in diverse populations: a metaanalysis. Am J Gastroenterol 99:2393–2404

    PubMed  CAS  Google Scholar 

  25. Pierik M, Joossens S, Van Steen K et al (2006) Toll-like receptor-1, -2, and -6 polymorphisms influence disease extension in inflammatory bowel diseases. Inflamm Bowel Dis 12:1–8

    PubMed  Google Scholar 

  26. van Heel DA, Fisher SA, Kirby A et al (2004) Inflammatory bowel disease susceptibility loci defined by genome scan meta-analysis of 1952 affected relative pairs. Hum Mol Genet 13:763–770

    PubMed  Google Scholar 

  27. Duerr RH, Taylor KD, Brant SR et al (2006) A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science 314:1461–1463

    PubMed  CAS  Google Scholar 

  28. Glas J, Seiderer J, Wetzke M et al (2007) rs1004819 is the main disease-associated IL23R variant in German Crohn’s disease patients: combined analysis of IL23R, CARD15, and OCTN1/2 variants. PLoS One 2:e819

    PubMed  Google Scholar 

  29. Fisher SA, Tremelling M, Anderson CA et al (2008) Genetic determinants of ulcerative colitis include the ECM1 locus and five loci implicated in Crohn’s disease. Nat Genet 40:710–712

    PubMed  CAS  Google Scholar 

  30. Taylor KD, Targan SR, Mei L et al (2008) IL23R haplotypes provide a large population attributable risk for Crohn’s disease. Inflamm Bowel Dis 14:1185–1191

    PubMed  Google Scholar 

  31. Stoll M, Corneliussen B, Costello CM et al (2004) Genetic variation in DLG5 is associated with inflammatory bowel disease. Nat Genet 36:476–480

    PubMed  CAS  Google Scholar 

  32. Kaser A, Lee AH, Franke A et al (2008) XBP1 links ER stress to intestinal inflammation and confers genetic risk for human inflammatory bowel disease. Cell 134:743–756

    PubMed  CAS  Google Scholar 

  33. Zhernakova A, Festen EM, Franke L et al (2008) Genetic analysis of innate immunity in Crohn’s disease and ulcerative colitis identifies two susceptibility loci harboring CARD9 and IL18RAP. Am J Hum Genet 82:1202–1210

    PubMed  CAS  Google Scholar 

  34. Glocker EO, Kotlarz D, Boztug K et al (2009) Inflammatory bowel disease and mutations affecting the interleukin-10 receptor. N Engl J Med 361:2033–2045

    PubMed  CAS  Google Scholar 

  35. Glocker EO, Frede N, Perro M, et al. Severe early-onset colitis due to a mutation in interleukin-10. The Lancet (accepted)

  36. Akman IO, Ostrov BE, Neudorf S (1998) Autoimmune manifestations of the Wiskott–Aldrich syndrome. Semin Arthritis Rheum 27:218–225

    PubMed  CAS  Google Scholar 

  37. Marks DJB, Segal AW (2008) Innate immunity in inflammatory bowel disease: a disease hypothesis. J Pathol 214:260–266

    PubMed  CAS  Google Scholar 

  38. Marks DJB, Miyagi K, Rahman FZ et al (2009) Inflammatory bowel disease in CGD reproduces the clinicopathological features of Crohn’s disease. Am J Gastroenterol 104:117–124

    PubMed  CAS  Google Scholar 

  39. Rahman FZ, Marks DJB, Hayee BH et al (2008) Phagocytic dysfunction and inflammatory bowel disease. Inflamm Bowel Dis 14:1443–1452

    PubMed  Google Scholar 

  40. Bouma G, Strober W (2003) The immunological and genetic basis of inflammatory bowel disease. Nat Rev Immunol 3:521–533

    PubMed  CAS  Google Scholar 

  41. Segal AW, Loewi G (1976) Neutrophil dysfunction in Crohn’s disease. Lancet 308:219–221

    Google Scholar 

  42. Marks DJB, Harbord MWN, MacAllister R et al (2006) Defective acute inflammation in Crohn’s disease: a clinical investigation. Lancet 367:668–678

    PubMed  CAS  Google Scholar 

  43. Smith AM, Rahman FZ, Hayee BH et al (2009) Disordered macrophage cytokine secretion underlies impaired acute inflammation and bacterial clearance in Crohn’s disease. J Exp Med 206:1883–1897

    PubMed  CAS  Google Scholar 

  44. Casanova JL, Abel L (2009) Revisiting Crohn’s disease as a primary immunodeficiency of macrophages. J Exp Med 206:1839–1843

    PubMed  CAS  Google Scholar 

  45. Ephgrave K (2007) Extra-intestinal manifestations of Crohn’s disease. Surg Clin North Am 87:673–680

    PubMed  Google Scholar 

  46. Moore KW, de Waal Malefyt R, Coffman RL, O’Garra A (2001) Interleukin-10 and the interleukin-10 receptor. Annu Rev Immunol 19:683–765

    PubMed  CAS  Google Scholar 

  47. Bogdan C, Vodovotz Y, Nathan C (1991) Macrophage deactivation by interleukin 10. J Exp Med 174:1549–1555

    PubMed  CAS  Google Scholar 

  48. de Waal Malefyt R, Haanen J, Spits H et al (1991) Interleukin-10 (IL-10) and viral IL-10 strongly reduce antigen-specific human T cell proliferation by diminishing the antigen-presenting capacity of monocytes via down regulation of class II major histocompatibility complex expression. J Exp Med 174:915–924

    PubMed  Google Scholar 

  49. Williams LM, Ricchetti G, Sarma U et al (2004) Interleukin-10 suppression of myeloid cell activation—a continuing puzzle. Immunology 113:281–292

    PubMed  CAS  Google Scholar 

  50. Kühn R, Lohler J, Rennick D et al (1993) Interleukin-10-deficient mice develop chronic enterocolitis. Cell 75:263–274

    PubMed  Google Scholar 

  51. Berg DJ, Kühn R, Rajewsky K et al (1995) Interleukin-10 is a central regulator of the response to LPS in murine models of endotoxic shock and the Shwartzman reaction but not endotoxin tolerance. J Clin Invest 96:2339–2347

    PubMed  CAS  Google Scholar 

  52. Franke A, Balschun T, Karlsen TH et al (2008) Sequence variants in IL10, ARPC2 and multiple other loci contribute to ulcerative colitis susceptibility. Nat Genet 40:1319–1323

    PubMed  CAS  Google Scholar 

  53. van der Linde K, Boor PP, Sandkuijl LA et al (2003) A Gly15Arg mutation in the interleukin-10 gene reduces secretion of interleukin-10 in Crohn disease. Scand J Gastroenterol 38:611–617

    PubMed  Google Scholar 

  54. Noguchi E, Homma Y, Kang X et al (2009) A Crohn’s disease-associated NOD2 mutation suppresses transcription of human IL10 by inhibiting activity of the nuclear ribonucleoprotein hnRNP-A1. Nat Immunol 10:471–479

    PubMed  CAS  Google Scholar 

  55. Girardin SE, Hugot JP, Sansonetti PJ (2003) Lessons from Nod2 studies: towards a link between Crohn’s disease and bacterial sensing. Trends Immunol 24:652–658

    PubMed  CAS  Google Scholar 

  56. Ogura Y, Bonen DK, Inohara N et al (2001) A frameshift mutation in NOD2 associated with susceptibility to Crohn’s disease. Nature 411:603–606

    PubMed  CAS  Google Scholar 

  57. Donnelly RP, Dickensheets H, Finbloom DS (1999) The interleukin-10 signal transduction pathway and regulation of gene expression in mononuclear phagocytes. J Interferon Cytokine Res 19:563–573

    PubMed  CAS  Google Scholar 

  58. Kotenko SV, Krause CD, Izotova LS et al (1997) Identification and functional characterization of a second chain of the interleukin-10 receptor complex. The EMBO J 16:5894–5903

    CAS  Google Scholar 

  59. O’Shea JJ, Murray PJ (2008) Cytokine signaling modules in inflammatory responses. Immunity 28:477–487

    PubMed  Google Scholar 

  60. Williams L, Bradley L, Smith A, Foxwell B (2004) Signal transducer and activator of transcription 3 is the dominant mediator of the anti-inflammatory effects of IL-10 in human macrophages. J Immunol 172:567–576

    PubMed  CAS  Google Scholar 

  61. Wolk K, Sabat R (2006) Interleukin-22: A novel T- and NK-cell derived cytokine that regulates the biology of tissue cells. Cytokine & Growth Factor Rev 17:367–380

    CAS  Google Scholar 

  62. Commins S, Steinke JW, Borish L (2008) The extended IL-10 superfamily: IL-10, IL-19, IL-20, IL-22, IL-24, IL-26, IL-28, and IL-29. J Allergy Clin Immunol 121:1108–1111

    PubMed  CAS  Google Scholar 

  63. Donnelly RP, Sheikh F, Kotenko SV, Dickensheets H (2004) The expanded family of class II cytokines that share the IL-10 receptor-2(IL-10R2) chain. J Leukoc Biol 76:314–321

    PubMed  CAS  Google Scholar 

  64. Sugimoto K, Ogawa A, Mizoguchi E et al (2008) IL-22 ameliorates intestinal inflammation in a mouse model of ulcerative colitis. J Clin Invest 118:534–544

    PubMed  CAS  Google Scholar 

  65. Zenewicz LA, Yancopoulos GD, Valenzuela DM et al (2008) Innate and adaptive interleukin-22 protects mice from inflammatory bowel disease. Immunity 29:947–957

    PubMed  CAS  Google Scholar 

  66. Zheng Y, Valdez PA, Danilenko DM et al (2008) Interleukin-22 mediates early host defense against attaching and effacing bacterial pathogens. Nat Med 14:282–289

    PubMed  CAS  Google Scholar 

  67. Wolk K, Kunz S, Witte E, Friedrich M, Asadullah K, Sabat R (2004) IL-22 increases the innate immunity of tissues. Immunity 21:241–254

    PubMed  CAS  Google Scholar 

  68. Wolk K, Witte E, Wallace E, Döcke WD, Kunz S, Asadullah K, Volk HD, Sterry W, Sabat R (2006) IL-22 regulates the expression of genes responsible for antimicrobial defense, cellular differentiation, and mobility in keratinocytes: a potential role in psoriasis. Eur J Immunol 36:1309–1323

    PubMed  CAS  Google Scholar 

  69. Kolls JK, McCray PB Jr, Chan YR (2008) Cytokine-mediated regulation of antimicrobial proteins. Nat Rev Immunol 8:829–835

    PubMed  CAS  Google Scholar 

  70. Kotenko SV, Gallagher G, Baurin VV et al (2003) IFN-λs mediate antiviral protection through a distinct class II cytokine receptor complex. Nat Immunol 4:69–77

    PubMed  CAS  Google Scholar 

  71. Sheppard P, Kindsvogel W, Xu W et al (2003) IL-28, IL-29 and their class II cytokine receptor IL-28R. Nat Immunol 4:63–68

    PubMed  CAS  Google Scholar 

  72. Maloy KJ, Salaun L, Cahill R et al (2003) CD4 + CD25 + T(R) cells suppress innate immune pathology through cytokine-dependent mechanisms. J Exp Med 197:111–119

    PubMed  CAS  Google Scholar 

  73. Read S, Malmström V, Powrie F (2000) Cytotoxic T lymphocyte-associated antigen 4 plays an essential role in the function of CD25(+)CD4(+) regulatory cells that control intestinal inflammation. J Exp Med 192:295–302

    PubMed  CAS  Google Scholar 

  74. Mottet C, Uhlig HH, Powrie F (2003) Cutting edge: cure of colitis by CD4+ CD25+ regulatory T cells. J Immunol 170:3939–3943

    PubMed  CAS  Google Scholar 

  75. Feuerer M, Hill JA, Mathis D, Benoist C (2009) Foxp3+ regulatory T cells: differentiation, specification, subphenotypes. Nat Immunol 10:689–695

    PubMed  CAS  Google Scholar 

  76. Josefowicz SZ, Rudensky A (2009) Control of regulatory T cell lineage commitment and maintenance. Immunity 30:616–625

    PubMed  CAS  Google Scholar 

  77. Lio CW, Hsieh CS (2008) A two-step process for thymic regulatory T cell development. Immunity 28:100–111

    PubMed  CAS  Google Scholar 

  78. Powrie F, Leach MW, Mauze S et al (1993) Phenotypically distinct subsets of CD4+ T cells induce or protect from chronic intestinal inflammation in C. B-17 scid mice. Int Immunol 5:1461–1471

    PubMed  CAS  Google Scholar 

  79. Bennett CL, Yoshioka R, Kiyosawa H et al (2000) X-Linked syndrome of polyendocrinopathy, immune dysfunction, and diarrhea maps to Xp11.23–Xq13.3. Am J Hum Genet 66:461–468

    PubMed  CAS  Google Scholar 

  80. Powell BR, Buist NR, Stenzel P (1982) An X-linked syndrome of diarrhea, polyendocrinopathy, and fatal infection in infancy. J Pediatr 100:731–737

    PubMed  CAS  Google Scholar 

  81. Ziegler SF (2006) FOXP3: of mice and men. Annu Rev Immunol 24:209–226

    PubMed  CAS  Google Scholar 

  82. Moraes-Vasconcelos D, Costa-Carvalho BT, Torgerson TR, Ochs HD (2008) Primary immune deficiency disorders presenting as autoimmune diseases: IPEX and APECED. J Clin Immunol 28(Suppl 1):S11–S19

    PubMed  CAS  Google Scholar 

  83. Gambineri E, Torgerson TR, Ochs HD (2003) Immune dysregulation, polyendocrinopathy, enteropathy, and X-linked inheritance (IPEX), a syndrome of systemic autoimmunity caused by mutations of FOXP3, a critical regulator of T cell homeostasis. Curr Opin Rheumatol 15:430–435

    PubMed  CAS  Google Scholar 

  84. Nieves DS, Phipps RP, Pollock SJ et al (2004) Dermatologic and immunologic findings in the immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome. Arch Dermatol 140:466–472

    PubMed  Google Scholar 

  85. Torgerson TR, Ochs HD (2007) Immune dysregulation, polyendocrinopathy, enteropathy, X-linked: forkhead box protein 3 mutations and lack of regulatory T cells. J Allergy Clin Immunol 120:744–750

    PubMed  CAS  Google Scholar 

  86. Heltzer ML, Choi JK, Ochs HD et al (2007) A potential screening tool for IPEX syndrome. Pediatr Dev Pathol 10:98–105

    PubMed  CAS  Google Scholar 

  87. Bennett CL, Ochs HD (2001) IPEX is a unique X-linked syndrome characterized by immune dysfunction, polyendocrinopathy, enteropathy, and a variety of autoimmune phenomena. Curr Opin Pediatr 13:533–538

    PubMed  CAS  Google Scholar 

  88. Costa-Carvalho BT, de Moraes-Pinto MI, de Almeida LC et al (2008) A remarkable depletion of both naïve CD4+ and CD8+ with high proportion of memory T cells in an IPEX infant with a FOXP3 mutation in the forkhead domain. Scand J Immunol 68:85–91

    PubMed  CAS  Google Scholar 

  89. Watanabe N, Wang YH, Lee HK et al (2005) Hassall’s corpuscles instruct dendritic cells to induce CD4+ CD25+ regulatory T cells in human thymus. Nature 436:1181–1185

    PubMed  CAS  Google Scholar 

  90. Korzenik JR (2007) Is Crohn’s disease due to defective immunity? Gut 56:2–5

    PubMed  CAS  Google Scholar 

  91. Thrasher AJ, Keep NH, Wientjes F, Segal AW (1994) Chronic granulomatous disease. Biochim Biophys Acta 1227:1–24

    PubMed  CAS  Google Scholar 

  92. Segal AW, Abo A (1993) The biochemical basis of the NADPH oxidase of phagocytes. Trends Biochem Sci 18:43–47

    PubMed  CAS  Google Scholar 

  93. Segal AW (2005) How neutrophils kill microbes. Annu Rev Immunol 23:197–223

    PubMed  CAS  Google Scholar 

  94. Segal BH, Romani LR (2009) Invasive aspergillosis in chronic granulomatous disease. Med Mycol 47(Suppl 1):S282–S290

    PubMed  CAS  Google Scholar 

  95. Stasia MJ, Li XJ (2008) Genetics and immunopathology of chronic granulomatous disease. Semin Immunopathol 30:209–235

    PubMed  Google Scholar 

  96. Werlin SL, Chusid MJ, Caya J, Oechler HW (1982) Colitis in chronic granulomatous disease. Gastroenterology 82:328–331

    PubMed  CAS  Google Scholar 

  97. Marciano BE, Rosenzweig SD, Kleiner DE et al (2004) Gastrointestinal involvement in chronic granulomatous disease. Pediatrics 114:462–468

    PubMed  Google Scholar 

  98. Westerberg LS, Meelu P, Baptista M et al (2010) Activating WASP mutations associated with X-linked neutropenia result in enhanced actin polymerization, altered cytoskeletal responses, and genomic instability in lymphocytes. J Exp Med 207:1145–1152

    PubMed  CAS  Google Scholar 

  99. Thrasher AJ, Burns SO (2010) WASP: a key immunological multitasker. Nat Rev Immunol 10:182–192

    PubMed  CAS  Google Scholar 

  100. Symons M, Derry JM, Karlak B et al (1996) Wiskott–Aldrich syndrome protein, a novel effector for the GTPase CDC42Hs, is implicated in actin polymerization. Cell 84:723–734

    PubMed  CAS  Google Scholar 

  101. Blanchoin L, Amann KJ, Higgs HN et al (2000) Direct observation of dendritic actin filament networks nucleated by Arp2/3 complex and WASP/Scar proteins. Nature 404:1007–1011

    PubMed  CAS  Google Scholar 

  102. Ochs HD, Thrasher AJ (2006) The Wiskott-Aldrich syndrome. J Allergy Clin Immunol 117:725–738

    PubMed  CAS  Google Scholar 

  103. Villa A, Notarangelo L, Macchi P et al (1995) X-linked thrombocytopenia and Wiskott–Aldrich syndrome are allelic diseases with mutations in the WASP gene. Nat Genet 9:414–417

    PubMed  CAS  Google Scholar 

  104. Notarangelo LD, Mazza C, Giliani S et al (2002) Missense mutations of the WASP gene cause intermittent X-linked thrombocytopenia. Blood 99:2268–2269

    PubMed  CAS  Google Scholar 

  105. Devriendt K, Kim AS, Mathijs G et al (2001) Constitutively activating mutation in WASP causes X-linked severe congenital neutropenia. Nat Genet 27:313–317

    PubMed  CAS  Google Scholar 

  106. Wiskott A (1937) Familiarer, angeborener Morbus Werlhofii? Monastsschr Kinderheilkd 68:212–216

    Google Scholar 

  107. Aldrich RA, Steinberg AG, Campbell DC (1954) Pedigree demonstrating a sex-linked recessive condition characterized by draining ears, eczematoid dermatitis and bloody diarrhea. Pediatrics 13:133–139

    PubMed  CAS  Google Scholar 

  108. Sullivan KE, Mullen CA, Blaese RM, Winkelstein JA (1994) A multiinstitutional survey of the Wiskott-Aldrich syndrome. J Pediatr 125:876–885

    PubMed  CAS  Google Scholar 

  109. Cannioto Z, Berti I, Martelossi S et al (2009) IBD and IBD mimicking enterocolitis in children younger than 2 years of age. Eur J Pediatr 168:149–155

    PubMed  CAS  Google Scholar 

  110. Dupuis-Girod S, Medioni J, Haddad E et al (2003) Autoimmunity in Wiskott–Aldrich syndrome: risk factors, clinical features, and outcome in a single-center cohort of 55 patients. Pediatrics 111(5 Pt 1):e622–e627

    PubMed  Google Scholar 

  111. Rohr J, Pannicke U, Döring M et al (2010) Chronic inflammatory bowel disease as key manifestation of atypical ARTEMIS deficiency. J Clin Immunol 30:314–320

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Medical Microbiology and Hygiene, University Medical Centre Freiburg, Hermann-Herder-Str. 11, 79104, Freiburg, Germany

    Erik Glocker

  2. Centre of Chronic Immunodeficiency, University Medical Centre Freiburg, Breisacher Straße 177 - 2nd floor, 79106, Freiburg, Germany

    Bodo Grimbacher

  3. Department of Immunology, University College London Medical School (Royal Free Campus), Rowland Hill Street, London, NW3 2PF, UK

    Bodo Grimbacher

Authors
  1. Erik Glocker
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bodo Grimbacher
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Erik Glocker or Bodo Grimbacher.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Glocker, E., Grimbacher, B. Inflammatory bowel disease: is it a primary immunodeficiency?. Cell. Mol. Life Sci. 69, 41–48 (2012). https://doi.org/10.1007/s00018-011-0837-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00018-011-0837-9

Keywords

Search

Navigation