Top

Published in:

01-03-2008 | Original Paper

Monozygous twins with a microdeletion syndrome involving BTK, DDP1, and two other genes; evidence of intact dendritic cell development and TLR responses

Authors: Harumi Jyonouchi, Lee Geng, Gökçe A. Törüner, Kavita Vinekar, Di Feng, Patricia Fitzgerald-Bocarsly

Published in: European Journal of Pediatrics | Issue 3/2008

Abstract

We report for the first time monozygous twins with a microdeletion syndrome involving genes coding for Bruton’s tyrosine kinase (Btk) and deafness-dystonia peptide 1 (DDP1), and two other genes. Apart from its essential role in B cell development, Btk is indicated to affect signaling mediated by toll like receptors (TLRs) and development of dendritic cells (DCs) but results are conflictive. The twins revealed normal numbers of plasmacytoid and myeloid DCs (pDCs and mDCs). Moreover, BTK null cells from these patients exhibited robust responses to TLR agonists, normal natural killer (NK) cell activity, and normal pDC functions.

Conclusion: Our results do not indicate the essential role of Btk in TLR signaling and DC development.

Bayry J, Lacroix-Desmazes S, Donkova-Petrini V, Carbonneil C, Misra N, Lepelletier Y, Delignat S, Varambally S, Oksenhendler E, Lévy Y, Debré M, Kazatchkine M, Hermine O, Kaveri SV (2004) Natural antibodies sustain differentiation and maturation of human dendritic cells. PNAS 101:14210–14215PubMedCrossRef

Binder J, Hofmann S, Kreisel S, Wohrle JC, Bazner H, Krauss JK, Hennerici MG, Bauer MF (2003) Clinical and molecular findings in a patient with novel mutation in the deafness-dystonia peptide (DDP1) gene. Brain 126:1814–1820PubMedCrossRef

Broides A, Yang W, Conley ME (2006) Genotype/phenotype correlations in X-linked agammaglobulinemia. Clin Immunol 118:195–200PubMedCrossRef

Feldman S, Stein D, Amrute S, Megjugorac N, Denny T, Garcia Z, Kloser P, Sun W, Fitzgerald-Bocarsly P (2001) Decreased IFN-alpha production in HIV infected patients correlates with numerical and functional deficiencies in circulating type 2 dendritic cell precursors. Clin Immunol 101:201–210PubMedCrossRef

Fitzgerald-Bocarsly P (2002) Plasmacytoid dendritic cells, the natural interferon alpha producing cells. BioTechniques 22:S16–S29

Gagliardi MC, Finocchi A, Orlandi P, Cursi L, Cancrini C, Moschese V, Miyawaki T, Rossi P (2003) Bruton’s tyrosine kinase defect in dedritic cells from X-linked agammaglobulinaemia patients does not influence their differentiation, maturation and antigen-presenting cell function. Clin Exp Immunol 133:115–122PubMedCrossRef

Horwood NJ, Mahon T, McDaid JP, Campbell J, Mano H, Brennan FM, Webster D, Foxwell BMJ (2003) Bruton’s tyrosine kinase is required for lipopolysaccharide-induced tumor necrosis factor α production. J Exp Med 197:1603–1611PubMedCrossRef

Horwood NJ, Page TH, McDaid JP, Palmer CD, Campbell J, Mahon T, Brennan FM, Webster D, Foxwell BM (2006) Bruton’s tyrosine kinase is required for TLR2 and TLR4-induced TNF, but not IL-6, production. J Immunol 176:3635–3641PubMed

Howell D, Fitzgerald-Bocarsly P (1991) Natural killer-mediated lysis of some, but not all, HSV-1- or VSV-infected targets requires the participation of HLA-DR-positive accessory cells. Immunology 72:443–447PubMed

10.

Jyonouchi H, Geng L, Ruby A, Zimmerman-Bier B (2005) Dysregulated innate immune responses in young children with Autism Spectrum Disorders (ASD): their relationship to Gastrointestinal (GI) symptoms and dietary intervention. Neuropsychobiology 51:77–85PubMedCrossRef

11.

Lund J, Sato A, Akira S, Medzhitov R, Iwasaki A (2003) Toll-like receptor 9-mediated recognition of herpes simplex virus-2 by plasmacytoid dendritic cells. J Exp Med 198:513–520PubMedCrossRef

12.

López-Granados E, Pérez de Diego R, Cerdán AF, Casariego GF, Rodriguez MCG (2005) A genotype-phenotype correlation study in a group of 54 patients with X-linked agmamaglobulinemia. J Allergy Clin Immunol 116:690–697PubMedCrossRef

13.

Mangla A, Khare A, Vineeth V, Panday NN, Mukhopadhyay A, Ravindran B, Bal V, George A, Rath S (2004) Pleiotrophic consequences of Bruton tyrosine kinase deficiency in myeloid lineages lead to poor inflammatory responses. Blood 104:1191–1197PubMedCrossRef

14.

Megjugorac NJ, Young HA, Amrute SB, Olshalsky SL, Fitzgerald-Bocarsly P (2004) Virally stimulated plasmacytoid dendritic cells produce chemokines and induce migration of T and NK cells. J Leukoc Biol 75:504–514PubMedCrossRef

15.

Mukhopadhyay S, Mohanty M, Mangla A, George A, Bal V, Rath S, Ravindran B (2002) Macrophage effector functions controlled by Bruton’s tyrosine kinase are more crucial than the cytokine balance of T cell responses for microfilarial clearance. J Immunol 168:2914–2921PubMed

16.

Pérez de Diego R, López-Granados E, Pozo M, Rodriguez C, Sabina P, Ferreira A, Fontan G, García-Rodriguez MC, Alemany S (2006) Bruton’s tyrosine kinase is not essential for LPS-induced activation of human monocytes. J Allergy Clin Immunol 117:1462–1469PubMedCrossRef

17.

Richter D, Conley ME, Rohrer J, Myers LA, Zahradka K, Kelečić J, Sertić J, Stavljenić-Rukavina A (2001) A contiguous deletion syndrome of X-linked agammaglobulinemia and sensorineural deafness. Pediatr Allergy Immunol 12:107–111PubMedCrossRef

18.

Schmidt NW, Thieu VT, Mann BA, Ahyi AN, Kaplan MH (2006) Bruton’s tyrosine kinase is required for TLR-induced IL-10 production. J Immunol 177:7203–7210PubMed

19.

Sherman DL, Fabrizi C, Gillespie CS, Brophy PJ (2001) Specific disruption of a schwann cell dystrophin-related protein complex in a demyelinating neuropathy. Neuron 30:677–687PubMedCrossRef

20.

Sochorva K, Horvath R, Rozkova D, Litzman J, Bartunkova J, Sediva A, Spiesek R (2006) Impaired Toll-like receptor 8-mediated IL-6 and TNF-α production in antigen presenting cells from patients with X-linked agammaglobulinaemia. Blood 7 [Epub ahead of print]

21.

Toruner GA, Streck DL, Schwalb MN, Dermody JJ (2007) An oligonucleotide based array-CGH system for detection of genome wide copy number changes including subtelomeric regions for genetic evaluation of mental retardation. Am J Med Genet A (in press)

22.

Turvey SE, Hawn TR (2006) Towards subtlety: understanding the role of Toll-like receptor signaling in susceptibility to human infections. Clin Immunol 120:1–9PubMedCrossRef

23.

Wang PJ, McCarrey JR, Yang F, Page DC (2001) An abundance of X-linked genes expressed in spermatogonia. Nat Genet 27:422–426PubMedCrossRef

24.

Winkelstein JA, Marino MC, Lederman HM, Jones SM, Sullivan K, Burks AW, Conley ME, Cunningham-Rundles C, Ochs HD (2006) X-linked agammaglobulinemia: report on a United States registry of 201 patients. Medicine 85:193–202PubMedCrossRef

25.

Yang WC, Collette Y, Nunes JA, Oliver D (2000) Tec kinases: a family with multiple roles in immunity. Immunity 12:373–382PubMedCrossRef

Title: Monozygous twins with a microdeletion syndrome involving BTK, DDP1, and two other genes; evidence of intact dendritic cell development and TLR responses
Authors: Harumi Jyonouchi
Lee Geng
Gökçe A. Törüner
Kavita Vinekar
Di Feng
Patricia Fitzgerald-Bocarsly
Publication date: 01-03-2008
Publisher: Springer-Verlag
Published in: European Journal of Pediatrics / Issue 3/2008
Print ISSN: 0340-6199
Electronic ISSN: 1432-1076
DOI: https://doi.org/10.1007/s00431-007-0493-0

At a glance: The STEP trials

Springer Medicine

Monozygous twins with a microdeletion syndrome involving BTK, DDP1, and two other genes; evidence of intact dendritic cell development and TLR responses

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 3/2008

Arginine-vasopressin as a rescue therapy in children and neonates for catecholamine-resistant shock

The predictive value of the pediatric symptom checklist in 5-year-old Austrian children

An estimation of indirect costs caused by acute rotavirus gastroenteritis in a Galician area, Spain

Is Familial Mediterranean Fever a thrombotic disease or not?

Ventilator assessment of respiratory mechanics in paediatric intensive care

Moebius-Poland syndrome and hypogonadotropic hypogonadism