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Erschienen in: Monatsschrift Kinderheilkunde 9/2009

01.09.2009 | Leitthema

Angeborene Immundefekte als Multisystemerkrankungen

verfasst von: Dr. E.D. Renner, N. Rieber, C. Klein, M.H. Albert

Erschienen in: Monatsschrift Kinderheilkunde | Ausgabe 9/2009

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Zusammenfassung

Primäre Immundefekte können sich nicht nur durch eine pathologische Infektionsanfälligkeit, sondern auch mit charakteristischen Krankheitszeichen an anderen Organsystemen manifestieren. Diese Auffälligkeiten an Knochen, Zähnen, Haaren und der Haut können Leitsymptome für die Diagnosestellung des zugrunde liegenden primären Immundefektes sein. Der vorliegende Beitrag erläutert einige dieser Multisystemerkrankungen mit Immundefekt von der Definition über die Diagnosestellung zu aktuellen Therapiemöglichkeiten.
Literatur
1.
Zurück zum Zitat Albert MH, Gennery AR, Greil J et al (2009) Successful stem cell transplantation for Nijmegen breakage syndrome. Bone Marrow Transplant Albert MH, Gennery AR, Greil J et al (2009) Successful stem cell transplantation for Nijmegen breakage syndrome. Bone Marrow Transplant
2.
Zurück zum Zitat Berthet F, Siegrist CA, Ozsahin H et al (1996) Bone marrow transplantation in cartilage-hair hypoplasia: correction of the immunodeficiency but not of the chondrodysplasia. Eur J Pediatr 155:286–290CrossRefPubMed Berthet F, Siegrist CA, Ozsahin H et al (1996) Bone marrow transplantation in cartilage-hair hypoplasia: correction of the immunodeficiency but not of the chondrodysplasia. Eur J Pediatr 155:286–290CrossRefPubMed
3.
Zurück zum Zitat Borges WG, Augustine NH, Hill HR (2000) Defective interleukin-12/interferon-gamma pathway in patients with hyperimmunoglobulinemia E syndrome. J Pediatr 136:176–180CrossRefPubMed Borges WG, Augustine NH, Hill HR (2000) Defective interleukin-12/interferon-gamma pathway in patients with hyperimmunoglobulinemia E syndrome. J Pediatr 136:176–180CrossRefPubMed
4.
Zurück zum Zitat Boztug K, Dewey RA, Klein C (2006) Development of hematopoietic stem cell gene therapy for Wiskott-Aldrich syndrome. Curr Opin Mol Ther 8:390–395PubMed Boztug K, Dewey RA, Klein C (2006) Development of hematopoietic stem cell gene therapy for Wiskott-Aldrich syndrome. Curr Opin Mol Ther 8:390–395PubMed
5.
Zurück zum Zitat Buckley RH, Wray BB, Belmaker EZ (1972) Extreme hyperimmunoglobulinemia E and undue susceptibility to infection. Pediatrics 49:59–70PubMed Buckley RH, Wray BB, Belmaker EZ (1972) Extreme hyperimmunoglobulinemia E and undue susceptibility to infection. Pediatrics 49:59–70PubMed
6.
Zurück zum Zitat Castigli E, Irani AM, Geha RS et al (1995) Defective expression of early activation genes in cartilage-hair hypoplasia (CHH) with severe combined immunodeficiency (SCID). Clin Exp Immunol 102:6–10PubMedCrossRef Castigli E, Irani AM, Geha RS et al (1995) Defective expression of early activation genes in cartilage-hair hypoplasia (CHH) with severe combined immunodeficiency (SCID). Clin Exp Immunol 102:6–10PubMedCrossRef
7.
Zurück zum Zitat Chavanas S, Bodemer C, Rochat A et al (2000) Mutations in SPINK5, encoding a serine protease inhibitor, cause Netherton syndrome. Nat Genet 25:141–142CrossRefPubMed Chavanas S, Bodemer C, Rochat A et al (2000) Mutations in SPINK5, encoding a serine protease inhibitor, cause Netherton syndrome. Nat Genet 25:141–142CrossRefPubMed
8.
Zurück zum Zitat Devriendt K, Kim AS, Mathijs G et al (2001) Constitutively activating mutation in WASP causes X-linked severe congenital neutropenia. Nat Genet 27:313–317CrossRefPubMed Devriendt K, Kim AS, Mathijs G et al (2001) Constitutively activating mutation in WASP causes X-linked severe congenital neutropenia. Nat Genet 27:313–317CrossRefPubMed
9.
Zurück zum Zitat Greene Sl, Muller SA (1985) Netherton’s syndrome. Report of a case and review of the literature. J Am Acad Dermatol 13:329–337CrossRefPubMed Greene Sl, Muller SA (1985) Netherton’s syndrome. Report of a case and review of the literature. J Am Acad Dermatol 13:329–337CrossRefPubMed
10.
Zurück zum Zitat Grimbacher B, Holland SM, Gallin JI et al (1999) Hyper-IgE syndrome with recurrent infections – an autosomal dominant multisystem disorder. N Engl J Med 340:692–702CrossRefPubMed Grimbacher B, Holland SM, Gallin JI et al (1999) Hyper-IgE syndrome with recurrent infections – an autosomal dominant multisystem disorder. N Engl J Med 340:692–702CrossRefPubMed
11.
Zurück zum Zitat Group Tinbss (2000) Nijmegen breakage syndrome. Arch Dis Child 82:400–406CrossRef Group Tinbss (2000) Nijmegen breakage syndrome. Arch Dis Child 82:400–406CrossRef
12.
Zurück zum Zitat Holland SM, Deleo FR, Elloumi HZ et al (2007) STAT3 mutations in the hyper-IgE syndrome. N Engl J Med 357:1608–1619CrossRefPubMed Holland SM, Deleo FR, Elloumi HZ et al (2007) STAT3 mutations in the hyper-IgE syndrome. N Engl J Med 357:1608–1619CrossRefPubMed
13.
Zurück zum Zitat Jayakumar A, Kang Y, Henderson Y et al (2005) Consequences of C-terminal domains and N-terminal signal peptide deletions on LEKTI secretion, stability, and subcellular distribution. Arch Biochem Biophys 435:89–102CrossRefPubMed Jayakumar A, Kang Y, Henderson Y et al (2005) Consequences of C-terminal domains and N-terminal signal peptide deletions on LEKTI secretion, stability, and subcellular distribution. Arch Biochem Biophys 435:89–102CrossRefPubMed
14.
Zurück zum Zitat Jones SK, Thomason LM, Surbrugg SK et al (1986) Neonatal hypernatraemia in two siblings with Netherton’s syndrome. Br J Dermatol 114:741–743CrossRefPubMed Jones SK, Thomason LM, Surbrugg SK et al (1986) Neonatal hypernatraemia in two siblings with Netherton’s syndrome. Br J Dermatol 114:741–743CrossRefPubMed
15.
Zurück zum Zitat Judge MR, Morgan G, Harper JI (1994) A clinical and immunological study of Netherton’s syndrome. Br J Dermatol 131:615–621CrossRefPubMed Judge MR, Morgan G, Harper JI (1994) A clinical and immunological study of Netherton’s syndrome. Br J Dermatol 131:615–621CrossRefPubMed
16.
Zurück zum Zitat Katugampola RP, Finlay AY, Harper JI et al (2005) Primary cutaneous CD30+ T-cell lymphoproliferative disorder following cardiac transplantation in a 15-year-old boy with Netherton’s syndrome. Br J Dermatol 153:1041–1046CrossRefPubMed Katugampola RP, Finlay AY, Harper JI et al (2005) Primary cutaneous CD30+ T-cell lymphoproliferative disorder following cardiac transplantation in a 15-year-old boy with Netherton’s syndrome. Br J Dermatol 153:1041–1046CrossRefPubMed
17.
Zurück zum Zitat Kavadas FD, Giliani S, Gu Y et al (2008) Variability of clinical and laboratory features among patients with ribonuclease mitochondrial RNA processing endoribonuclease gene mutations. J Allergy Clin Immunol 122:1178–1184CrossRefPubMed Kavadas FD, Giliani S, Gu Y et al (2008) Variability of clinical and laboratory features among patients with ribonuclease mitochondrial RNA processing endoribonuclease gene mutations. J Allergy Clin Immunol 122:1178–1184CrossRefPubMed
18.
Zurück zum Zitat Land MH, Garcia-Lloret MI, Borzy MS et al (2007) Long-term results of bone marrow transplantation in complete DiGeorge syndrome. J Allergy Clin Immunol 120:908–915CrossRefPubMed Land MH, Garcia-Lloret MI, Borzy MS et al (2007) Long-term results of bone marrow transplantation in complete DiGeorge syndrome. J Allergy Clin Immunol 120:908–915CrossRefPubMed
19.
Zurück zum Zitat Levy DE, Lee CK (2002) What does Stat3 do? J Clin Invest 109:1143–1148PubMed Levy DE, Lee CK (2002) What does Stat3 do? J Clin Invest 109:1143–1148PubMed
20.
Zurück zum Zitat Magert HJ, Kreutzmann P, Standker L et al (2002) LEKTI: a multidomain serine proteinase inhibitor with pathophysiological relevance. Int J Biochem Cell Biol 34:573–576CrossRefPubMed Magert HJ, Kreutzmann P, Standker L et al (2002) LEKTI: a multidomain serine proteinase inhibitor with pathophysiological relevance. Int J Biochem Cell Biol 34:573–576CrossRefPubMed
21.
Zurück zum Zitat Makitie O, Kaitila I, Savilahti E (2000) Deficiency of humoral immunity in cartilage-hair hypoplasia. J Pediatr 137:487–492CrossRefPubMed Makitie O, Kaitila I, Savilahti E (2000) Deficiency of humoral immunity in cartilage-hair hypoplasia. J Pediatr 137:487–492CrossRefPubMed
22.
Zurück zum Zitat Makitie O, Perheentupa J, Kaitila I (1992) Growth in cartilage-hair hypoplasia. Pediatr Res 31:176–180PubMed Makitie O, Perheentupa J, Kaitila I (1992) Growth in cartilage-hair hypoplasia. Pediatr Res 31:176–180PubMed
23.
Zurück zum Zitat Markert Ml, Devlin BH, Chinn IK et al (2009) Thymus transplantation in complete DiGeorge anomaly. Immunol Res 44:61–70CrossRefPubMed Markert Ml, Devlin BH, Chinn IK et al (2009) Thymus transplantation in complete DiGeorge anomaly. Immunol Res 44:61–70CrossRefPubMed
24.
Zurück zum Zitat Mckusick VA, Eldridge R, Hostetler JA et al (1965) Dwarfism in the Amish. Ii. Cartilage-Hair Hypoplasia. Bull Johns Hopkins Hosp 116:285–326PubMed Mckusick VA, Eldridge R, Hostetler JA et al (1965) Dwarfism in the Amish. Ii. Cartilage-Hair Hypoplasia. Bull Johns Hopkins Hosp 116:285–326PubMed
25.
Zurück zum Zitat Minegishi Y, Saito M, Morio T et al (2006) Human tyrosine kinase 2 deficiency reveals its requisite roles in multiple cytokine signals involved in innate and acquired immunity. Immunity 25:745–755CrossRefPubMed Minegishi Y, Saito M, Morio T et al (2006) Human tyrosine kinase 2 deficiency reveals its requisite roles in multiple cytokine signals involved in innate and acquired immunity. Immunity 25:745–755CrossRefPubMed
26.
Zurück zum Zitat Minegishi Y, Saito M, Tsuchiya S et al (2007) Dominant-negative mutations in the DNA-binding domain of STAT3 cause hyper-IgE syndrome. Nature 448:1058–1062CrossRefPubMed Minegishi Y, Saito M, Tsuchiya S et al (2007) Dominant-negative mutations in the DNA-binding domain of STAT3 cause hyper-IgE syndrome. Nature 448:1058–1062CrossRefPubMed
27.
Zurück zum Zitat Moin M, Farhoudi A, Movahedi M et al (2006) The clinical and laboratory survey of Iranian patients with hyper-IgE syndrome. Scand J Infect Dis 38:898–903CrossRefPubMed Moin M, Farhoudi A, Movahedi M et al (2006) The clinical and laboratory survey of Iranian patients with hyper-IgE syndrome. Scand J Infect Dis 38:898–903CrossRefPubMed
28.
Zurück zum Zitat Notarangelo LD, Roifman CM, Giliani S (2008) Cartilage-hair hypoplasia: molecular basis and heterogeneity of the immunological phenotype. Curr Opin Allergy Clin Immunol 8:534–539CrossRefPubMed Notarangelo LD, Roifman CM, Giliani S (2008) Cartilage-hair hypoplasia: molecular basis and heterogeneity of the immunological phenotype. Curr Opin Allergy Clin Immunol 8:534–539CrossRefPubMed
29.
Zurück zum Zitat Ochs HDS, Edward CI Puck, Jennifer M (2006) Primary immunodeficiency diseases: a molecular & cellular approach. Oxford University Press, USA, pp 518–524 Ochs HDS, Edward CI Puck, Jennifer M (2006) Primary immunodeficiency diseases: a molecular & cellular approach. Oxford University Press, USA, pp 518–524
30.
Zurück zum Zitat Polmar SH, Pierce GF (1986) Cartilage hair hypoplasia: immunological aspects and their clinical implications. Clin Immunol Immunopathol 40:87–93CrossRefPubMed Polmar SH, Pierce GF (1986) Cartilage hair hypoplasia: immunological aspects and their clinical implications. Clin Immunol Immunopathol 40:87–93CrossRefPubMed
31.
Zurück zum Zitat Renner ED, Hartl D, Rylaarsdam S et al (2009) Comèl-Netherton syndrome – defined as primary immunodeficiency J Allergy Clin Immunol (in press) Renner ED, Hartl D, Rylaarsdam S et al (2009) Comèl-Netherton syndrome – defined as primary immunodeficiency J Allergy Clin Immunol (in press)
32.
Zurück zum Zitat Renner ED, Puck JM, Holland SM et al (2004) Autosomal recessive hyperimmunoglobulin E syndrome: a distinct disease entity. J Pediatr 144:93–99CrossRefPubMed Renner ED, Puck JM, Holland SM et al (2004) Autosomal recessive hyperimmunoglobulin E syndrome: a distinct disease entity. J Pediatr 144:93–99CrossRefPubMed
33.
Zurück zum Zitat Renner ED, Rylaarsdam S, Anover-Sombke S et al (2008) Novel signal transducer and activator of transcription 3 (STAT3) mutations, reduced T(H)17 cell numbers, and variably defective STAT3 phosphorylation in hyper-IgE syndrome. J Allergy Clin Immunol 122:181–187CrossRefPubMed Renner ED, Rylaarsdam S, Anover-Sombke S et al (2008) Novel signal transducer and activator of transcription 3 (STAT3) mutations, reduced T(H)17 cell numbers, and variably defective STAT3 phosphorylation in hyper-IgE syndrome. J Allergy Clin Immunol 122:181–187CrossRefPubMed
34.
Zurück zum Zitat Ridanpaa M, Van Eenennaam H, Pelin K et al (2001) Mutations in the RNA component of RNase MRP cause a pleiotropic human disease, cartilage-hair hypoplasia. Cell 104:195–203CrossRefPubMed Ridanpaa M, Van Eenennaam H, Pelin K et al (2001) Mutations in the RNA component of RNase MRP cause a pleiotropic human disease, cartilage-hair hypoplasia. Cell 104:195–203CrossRefPubMed
35.
Zurück zum Zitat Thrasher AJ (2002) WASp in immune-system organization and function. Nat Rev Immunol 2:635–646CrossRefPubMed Thrasher AJ (2002) WASp in immune-system organization and function. Nat Rev Immunol 2:635–646CrossRefPubMed
36.
Zurück zum Zitat Van Gysel D, Koning H, Baert MR et al (2001) Clinico-immunological heterogeneity in Comel-Netherton syndrome. Dermatology 202:99–107CrossRef Van Gysel D, Koning H, Baert MR et al (2001) Clinico-immunological heterogeneity in Comel-Netherton syndrome. Dermatology 202:99–107CrossRef
37.
Zurück zum Zitat Varon R, Vissinga C, Platzer M et al (1998) Nibrin, a novel DNA double-strand break repair protein, is mutated in Nijmegen breakage syndrome. Cell 93:467–476CrossRefPubMed Varon R, Vissinga C, Platzer M et al (1998) Nibrin, a novel DNA double-strand break repair protein, is mutated in Nijmegen breakage syndrome. Cell 93:467–476CrossRefPubMed
38.
Zurück zum Zitat Wilkinson RD, Curtis GH, Hawk WA (1964) Netherton’s disease; trichorrhexis invaginata (bamboo hair), congenital ichthyosiform erythroderma and the atopic diathesis. A histopathologic study. Arch Dermatol 89:46–54PubMedCrossRef Wilkinson RD, Curtis GH, Hawk WA (1964) Netherton’s disease; trichorrhexis invaginata (bamboo hair), congenital ichthyosiform erythroderma and the atopic diathesis. A histopathologic study. Arch Dermatol 89:46–54PubMedCrossRef
39.
Zurück zum Zitat Wiskott A (1937) Familiärer, angeborener Morbus Werlhof? Monatsschr Kinderheilkd 68:212–216 Wiskott A (1937) Familiärer, angeborener Morbus Werlhof? Monatsschr Kinderheilkd 68:212–216
40.
Zurück zum Zitat Woellner C, Schaffer AA, Puck JM et al (2007) The hyper IgE syndrome and mutations in TYK2. Immunity 26:535; author reply 536CrossRefPubMed Woellner C, Schaffer AA, Puck JM et al (2007) The hyper IgE syndrome and mutations in TYK2. Immunity 26:535; author reply 536CrossRefPubMed
41.
Zurück zum Zitat Yagi H, Furutani Y, Hamada H et al (2003) Role of TBX1 in human del22q11.2 syndrome. Lancet 362:1366–1373CrossRefPubMed Yagi H, Furutani Y, Hamada H et al (2003) Role of TBX1 in human del22q11.2 syndrome. Lancet 362:1366–1373CrossRefPubMed
42.
Zurück zum Zitat Yel L, Aggarwal S, Gupta S (1999) Cartilage-hair hypoplasia syndrome: increased apoptosis of T lymphocytes is associated with altered expression of Fas (CD95), FasL (CD95L), IAP, Bax, and Bcl2. J Clin Immunol 19:428–434CrossRefPubMed Yel L, Aggarwal S, Gupta S (1999) Cartilage-hair hypoplasia syndrome: increased apoptosis of T lymphocytes is associated with altered expression of Fas (CD95), FasL (CD95L), IAP, Bax, and Bcl2. J Clin Immunol 19:428–434CrossRefPubMed
Metadaten
Titel
Angeborene Immundefekte als Multisystemerkrankungen
verfasst von
Dr. E.D. Renner
N. Rieber
C. Klein
M.H. Albert
Publikationsdatum
01.09.2009
Verlag
Springer-Verlag
Erschienen in
Monatsschrift Kinderheilkunde / Ausgabe 9/2009
Print ISSN: 0026-9298
Elektronische ISSN: 1433-0474
DOI
https://doi.org/10.1007/s00112-009-1987-9

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