Advertisement

Journal of Clinical Immunology

, Volume 35, Issue 2, pp 168–181 | Cite as

Infectious and Immunologic Phenotype of MECP2 Duplication Syndrome

  • Michael BauerEmail author
  • Uwe Kölsch
  • Renate Krüger
  • Nadine Unterwalder
  • Karin Hameister
  • Fabian Marc Kaiser
  • Aglaia Vignoli
  • Rainer Rossi
  • Maria Pilar Botella
  • Magdalena Budisteanu
  • Monica Rosello
  • Carmen Orellana
  • Maria Isabel Tejada
  • Sorina Mihaela Papuc
  • Oliver Patat
  • Sophie Julia
  • Renaud Touraine
  • Thusari Gomes
  • Kirsten Wenner
  • Xiu Xu
  • Alexandra Afenjar
  • Annick Toutain
  • Nicole Philip
  • Aleksandra Jezela-Stanek
  • Ludwig Gortner
  • Francisco Martinez
  • Bernard Echenne
  • Volker Wahn
  • Christian Meisel
  • Dagmar Wieczorek
  • Salima El-Chehadeh
  • Hilde Van Esch
  • Horst von BernuthEmail author
Original Research

Abstract

MECP2 (methyl CpG binding protein 2) duplication causes syndromic intellectual disability. Patients often suffer from life-threatening infections, suggesting an additional immunodeficiency. We describe for the first time the detailed infectious and immunological phenotype of MECP2 duplication syndrome. 17/27 analyzed patients suffered from pneumonia, 5/27 from at least one episode of sepsis. Encapsulated bacteria (S.pneumoniae, H.influenzae) were frequently isolated. T-cell immunity showed no gross abnormalities in 14/14 patients and IFNy-secretion upon ConA-stimulation was not decreased in 6/7 patients. In 6/21 patients IgG2-deficiency was detected – in 4/21 patients accompanied by IgA-deficiency, 10/21 patients showed low antibody titers against pneumococci. Supra-normal IgG1-levels were detected in 11/21 patients and supra-normal IgG3-levels were seen in 8/21 patients – in 6 of the patients as combined elevation of IgG1 and IgG3. Three of the four patients with IgA/IgG2-deficiency developed multiple severe infections. Upon infections pronounced acute-phase responses were common: 7/10 patients showed CRP values above 200 mg/l. Our data for the first time show systematically that increased susceptibility to infections in MECP2 duplication syndrome is associated with IgA/IgG2-deficiency, low antibody titers against pneumococci and elevated acute-phase responses. So patients with MECP2 duplication syndrome and low IgA/IgG2 may benefit from prophylactic substitution of sIgA and IgG.

Keywords

Xq28-duplication syndrome methyl CpG binding protein 2 (MECP2) MECP2 duplication syndrome primary immunodeficiency intellectual disability humoral immunodeficiency 

Abbreviations

MECP2

Methyl CpG binding protein 2

XLID

X linked intellectual disability

Notes

Acknowledgments

We thank the patients and their families for participating in this study and Margret Oberreit, Petra Ellensohn (deceased 01/2011), Christine Seib, Kristin Neuhaus, Anne-Hélène Lebrun and Karoline Strehl for discussions, critical reading of the manuscript and technical assistance. This work was supported by the German Research Foundation (DFG BE 3895/3-1), the Federal Ministry of Education and Research, Germany (BMBF PID-NET 01GM1111D/TP-A5) and the Sonnenfeld Stiftung, Berlin.

Supplementary material

10875_2015_129_MOESM1_ESM.pptx (207 kb)
Supplementary figure 1 Cellular immunological phenotype of patients with MECP2 duplication syndrome. A. Leucocytes. B. Monocytes. C. Neutrophilic leucocytes. D. Eosinophilic leucocytes. E. Basophilic leucocytes. (PPTX 207 kb)
10875_2015_129_MOESM2_ESM.pptx (129 kb)
Supplementary figure 2 Humoral immunological phenotype of patients with MECP2 duplication syndrome. IgG levels against Tetanus toxoid. (PPTX 129 kb)
10875_2015_129_MOESM3_ESM.pptx (65 kb)
Supplementary table 1 Data on duplications of previously non-published patients P11, P14, P16, P18 P19, P23, P24, P25, P26, P28, P29 and P30. (PPTX 64 kb)
10875_2015_129_MOESM4_ESM.pptx (55 kb)
Supplementary table 2 Infectious phenotype of patients with MECP2 duplication syndrome. Pathogens isolated and location of isolation. (PPTX 55 kb)
10875_2015_129_MOESM5_ESM.pptx (81 kb)
Supplementary table 3a Cellular immunological phenotype of patients with MECP2 duplication syndrome. Age group < 6 years and age group 6–10 years. Lymphocyte subsets are depicted in absolute numbers and percentages. Reference values for the respective age group are given. (PPTX 81 kb)
10875_2015_129_MOESM6_ESM.pptx (80 kb)
Supplementary table 3b Cellular immunological phenotype of patients with MECP2 duplication syndrome. Age group 10–18 years and age group >18 years. Lymphocyte subsets are depicted in absolute numbers and percentages. Reference values for the respective age group are given. (PPTX 80 kb)
10875_2015_129_MOESM7_ESM.pptx (66 kb)
Supplementary table 4 Cellular immunological phenotype of patients with MECP2 duplication syndrome. Lymphocyte proliferation assay. Proliferation is depicted as count per minute (cpm). (PPTX 66 kb)

References

  1. 1.
    Lubs H, Abidi F, Bier JA, Abuelo D, Ouzts L, Voeller K, et al. XLMR syndrome characterized by multiple respiratory infections, hypertelorism, severe CNS deterioration and early death localizes to distal Xq28. Am J Med Genet. 1999;85(3):243–8.CrossRefPubMedGoogle Scholar
  2. 2.
    Meins M, Lehmann J, Gerresheim F, Herchenbach J, Hagedorn M, Hameister K, et al. Submicroscopic duplication in Xq28 causes increased expression of the MECP2 gene in a boy with severe mental retardation and features of Rett syndrome. J Med Genet. 2005;42(2):e12.CrossRefPubMedCentralPubMedGoogle Scholar
  3. 3.
    Van Esch H, Bauters M, Ignatius J, Jansen M, Raynaud M, Hollanders K, et al. Duplication of the MECP2 region is a frequent cause of severe mental retardation and progressive neurological symptoms in males. Am J Hum Genet. 2005;77(3):442–53.CrossRefPubMedCentralPubMedGoogle Scholar
  4. 4.
    Ariani F, Mari F, Pescucci C, Longo I, Bruttini M, Meloni I, et al. Real-time quantitative PCR as a routine method for screening large rearrangements in Rett syndrome: report of one case of MECP2 deletion and one case of MECP2 duplication. Hum Mutat. 2004;24(2):172–7.CrossRefPubMedGoogle Scholar
  5. 5.
    Lugtenberg D, de Brouwer AP, Kleefstra T, Oudakker AR, Frints SG, Schrander-Stumpel CT, et al. Chromosomal copy number changes in patients with non-syndromic X linked mental retardation detected by array CGH. J Med Genet. 2006;43(4):362–70.CrossRefPubMedCentralPubMedGoogle Scholar
  6. 6.
    Friez MJ, Jones JR, Clarkson K, Lubs H, Abuelo D, Bier JA, et al. Recurrent infections, hypotonia, and mental retardation caused by duplication of MECP2 and adjacent region in Xq28. Pediatrics. 2006;118(6):e1687–95.CrossRefPubMedGoogle Scholar
  7. 7.
    del Gaudio D, Fang P, Scaglia F, Ward PA, Craigen WJ, Glaze DG, et al. Increased MECP2 gene copy number as the result of genomic duplication in neurodevelopmentally delayed males. Genet Med. 2006;8(12):784–92.CrossRefPubMedGoogle Scholar
  8. 8.
    Madrigal I, Rodríguez-Revenga L, Armengol L, González E, Rodriguez B, Badenas C, et al. X-chromosome tiling path array detection of copy number variants in patients with chromosome X-linked mental retardation. BMC Genomics. 2007;8:443.CrossRefPubMedCentralPubMedGoogle Scholar
  9. 9.
    Bauters M, Van Esch H, Friez MJ, Boespflug-Tanguy O, Zenker M, Vianna-Morgante AM, et al. Nonrecurrent MECP2 duplications mediated by genomic architecture-driven DNA breaks and break-induced replication repair. Genome Res. 2008;18(6):847–58.CrossRefPubMedCentralPubMedGoogle Scholar
  10. 10.
    Smyk M, Obersztyn E, Nowakowska B, Nawara M, Cheung SW, Mazurczak T, et al. Different-sized duplications of Xq28, including MECP2, in three males with mental retardation, absent or delayed speech, and recurrent infections. Am J Med Genet B Neuropsychiatr Genet. 2008;147B(6):799–806.CrossRefPubMedGoogle Scholar
  11. 11.
    Velinov M, Novelli A, Gu H, Fenko M, Dolzhanskaya N, Bernardini L, et al. De-novo 2.15 Mb terminal Xq duplication involving MECP2 but not L1CAM gene in a male patient with mental retardation. Clin Dysmorphol. 2009;18(1):9–12.CrossRefPubMedGoogle Scholar
  12. 12.
    Sanlaville D, Schluth-Bolard C, Turleau C. Distal Xq duplication and functional Xq disomy. Orphanet J Rare Dis. 2009;4:4.CrossRefPubMedCentralPubMedGoogle Scholar
  13. 13.
    Kirk EP, Malaty-Brevaud V, Martini N, Lacoste C, Levy N, Maclean K, et al. The clinical variability of the MECP2 duplication syndrome: description of two families with duplications excluding L1CAM and FLNA. Clin Genet. 2009;75(3):301–3.CrossRefPubMedGoogle Scholar
  14. 14.
    Clayton-Smith J, Walters S, Hobson E, Burkitt-Wright E, Smith R, Toutain A, et al. Xq28 duplication presenting with intestinal and bladder dysfunction and a distinctive facial appearance. Eur J Hum Genet. 2009;17(4):434–43.CrossRefPubMedCentralPubMedGoogle Scholar
  15. 15.
    Lugtenberg D, Kleefstra T, Oudakker AR, Nillesen WM, Yntema HG, Tzschach A, et al. Structural variation in Xq28: MECP2 duplications in 1% of patients with unexplained XLMR and in 2% of male patients with severe encephalopathy. Eur J Hum Genet. 2009;17(4):444–53.CrossRefPubMedCentralPubMedGoogle Scholar
  16. 16.
    Prescott TE, Rødningen OK, Bjørnstad A, Stray-Pedersen A. Two brothers with a microduplication including the MECP2 gene: rapid head growth in infancy and resolution of susceptibility to infection. Clin Dysmorphol. 2009;18(2):78–82.CrossRefPubMedGoogle Scholar
  17. 17.
    Carvalho CM, Zhang F, Liu P, Patel A, Sahoo T, Bacino CA, et al. Complex rearrangements in patients with duplications of MECP2 can occur by fork stalling and template switching. Hum Mol Genet. 2009;18(12):2188–203.CrossRefPubMedCentralPubMedGoogle Scholar
  18. 18.
    Echenne B, Roubertie A, Lugtenberg D, Kleefstra T, Hamel BC, Van Bokhoven H, et al. Neurologic aspects of MECP2 gene duplication in male patients. Pediatr Neurol. 2009;41(3):187–91.CrossRefPubMedGoogle Scholar
  19. 19.
    Vandewalle J, Van Esch H, Govaerts K, Verbeeck J, Zweier C, Madrigal I, et al. Dosage-dependent severity of the phenotype in patients with mental retardation due to a recurrent copy-number gain at Xq28 mediated by an unusual recombination. Am J Hum Genet. 2009;85(6):809–22.CrossRefPubMedCentralPubMedGoogle Scholar
  20. 20.
    Ramocki MB, Peters SU, Tavyev YJ, Zhang F, Carvalho CM, Schaaf CP, et al. Autism and other neuropsychiatric symptoms are prevalent in individuals with MeCP2 duplication syndrome. Ann Neurol. 2009;66(6):771–82.CrossRefPubMedCentralPubMedGoogle Scholar
  21. 21.
    Bartsch O, Gebauer K, Lechno S, van Esch H, Froyen G, Bonin M, et al. Four unrelated patients with Lubs X-linked mental retardation syndrome and different Xq28 duplications. Am J Med Genet A. 2010;152A(2):305–12.CrossRefPubMedGoogle Scholar
  22. 22.
    Campos Jr M, Churchman SM, Santos-Rebouças CB, Ponchel F, Pimentel MM. High frequency of nonrecurrent MECP2 duplications among Brazilian males with mental retardation. J Mol Neurosci. 2010;41(1):105–9.CrossRefPubMedGoogle Scholar
  23. 23.
    Belligni EF, Palmer RW, Hennekam RC. MECP2 duplication in a patient with congenital central hypoventilation. Am J Med Genet A. 2010;152A(6):1591–3.PubMedGoogle Scholar
  24. 24.
    Reardon W, Donoghue V, Murphy AM, King MD, Mayne PD, Horn N, et al. Progressive cerebellar degenerative changes in the severe mental retardation syndrome caused by duplication of MECP2 and adjacent loci on Xq28. Eur J Pediatr. 2010;169(8):941–9.CrossRefPubMedGoogle Scholar
  25. 25.
    Makrythanasis P, Moix I, Gimelli S, Fluss J, Aliferis K, Antonarakis SE, et al. De novo duplication of MECP2 in a girl with mental retardation and no obvious dysmorphic features. Clin Genet. 2010;78(2):175–80.CrossRefPubMedGoogle Scholar
  26. 26.
    Honda S, Hayashi S, Imoto I, Toyama J, Okazawa H, Nakagawa E, et al. Copy-number variations on the X chromosome in Japanese patients with mental retardation detected by array-based comparative genomic hybridization analysis. J Hum Genet. 2010;55(9):590–9.CrossRefPubMedGoogle Scholar
  27. 27.
    Fernández RM, Núñez-Torres R, González-Meneses A, Antiñolo G, Borrego S. Novel association of severe neonatal encephalopathy and Hirschsprung disease in a male with a duplication at the Xq28 region. BMC Med Genet. 2010;11:137.CrossRefPubMedCentralPubMedGoogle Scholar
  28. 28.
    Jezela-Stanek A, Ciara E, Juszczak M, Pelc M, Materna-Kiryluk A, Krajewska-Walasek M. Cryptic x; autosome translocation in a boy–delineation of the phenotype. Pediatr Neurol. 2011;44(3):221–4.CrossRefPubMedGoogle Scholar
  29. 29.
    Breman AM, Ramocki MB, Kang SH, Williams M, Freedenberg D, Patel A, et al. MECP2 duplications in six patients with complex sex chromosome rearrangements. Eur J Hum Genet. 2011;19(4):409–15.CrossRefPubMedCentralPubMedGoogle Scholar
  30. 30.
    Grasshoff U, Bonin M, Goehring I, Ekici A, Dufke A, Cremer K, et al. De novo MECP2 duplication in two females with random X-inactivation and moderate mental retardation. Eur J Hum Genet. 2011;19(5):507–12.CrossRefPubMedCentralPubMedGoogle Scholar
  31. 31.
    Budisteanu M, Papuc SM, Tutulan-Cunita A, Budisteanu B, Arghir A. Novel clinical finding in MECP2 duplication syndrome. Eur Child Adolesc Psychiatry. 2011;20(7):373–5.CrossRefPubMedGoogle Scholar
  32. 32.
    Mayo S, Monfort S, Roselló M, Orellana C, Oltra S, Armstrong J, et al. De novo interstitial triplication of MECP2 in a girl with neurodevelopmental disorder and random X chromosome inactivation. Cytogenet Genome Res. 2011;135(2):93–101.CrossRefPubMedGoogle Scholar
  33. 33.
    Carvalho CM, Ramocki MB, Pehlivan D, Franco LM, Gonzaga-Jauregui C, Fang P, et al. Inverted genomic segments and complex triplication rearrangements are mediated by inverted repeats in the human genome. Nat Genet. 2011;43(11):1074–81.CrossRefPubMedCentralPubMedGoogle Scholar
  34. 34.
    Tang SS, Fernandez D, Lazarou LP, Singh R, Fallon P. MECP2 triplication in 3 brothers - a rarely described cause of familial neurological regression in boys. Eur J Paediatr Neurol. 2012;16(2):209–12.CrossRefPubMedGoogle Scholar
  35. 35.
    Honda S, Satomura S, Hayashi S, Imoto I, Nakagawa E, Goto Y, et al. Japanese mental retardation consortium. Concomitant microduplications of MECP2 and ATRX in male patients with severe mental retardation. J Hum Genet. 2012;57(1):73–7.CrossRefPubMedGoogle Scholar
  36. 36.
    Utine GE, Kiper PO, Alanay Y, Haliloğlu G, Aktaş D, Boduroğlu K, et al. Searching for copy number changes in nonsyndromic X-linked intellectual disability. Mol Syndromol. 2012;2(2):64–71.PubMedCentralPubMedGoogle Scholar
  37. 37.
    Bijlsma EK, Collins A, Papa FT, Tejada MI, Wheeler P, Peeters EA, et al. Xq28 duplications including MECP2 in five females: expanding the phenotype to severe mental retardation. Eur J Med Genet. 2012;55(6–7):404–13.CrossRefPubMedGoogle Scholar
  38. 38.
    Honda S, Hayashi S, Nakane T, Imoto I, Kurosawa K, Mizuno S, et al. The incidence of hypoplasia of the corpus callosum in patients with dup (X)(q28) involving MECP2 is associated with the location of distal breakpoints. Am J Med Genet A. 2012;158A(6):1292–303.CrossRefPubMedGoogle Scholar
  39. 39.
    Sanmann JN, Bishay DL, Starr LJ, Bell CA, Pickering DL, Stevens JM, et al. Characterization of six novel patients with MECP2 duplications due to unbalanced rearrangements of the X chromosome. Am J Med Genet A. 2012;158A(6):1285–91.CrossRefPubMedGoogle Scholar
  40. 40.
    Vignoli A, Borgatti R, Peron A, Zucca C, Ballarati L, Bonaglia C, et al. Electroclinical pattern in MECP2 duplication syndrome: eight new reported cases and review of literature. Epilepsia. 2012;53(7):1146–55.CrossRefPubMedGoogle Scholar
  41. 41.
    Shimada S, Okamoto N, Ito M, Arai Y, Momosaki K, Togawa M, Maegaki Y, Sugawara M, Shimojima K, Osawa M, Yamamoto T. MECP2 duplication syndrome in both genders. Brain Dev. 2012.Google Scholar
  42. 42.
    Hanchard NA, Carvalho CM, Bader P, Thome A, Omo-Griffith L, Del Gaudio D, et al. A partial MECP2 duplication in a mildly affected adult male: a putative role for the 3′ untranslated region in the MECP2 duplication phenotype. BMC Med Genet. 2012;13:71.CrossRefPubMedCentralPubMedGoogle Scholar
  43. 43.
    Xu X, Xu Q, Zhang Y, Zhang X, Cheng T, Wu B, et al. A case report of Chinese brothers with inherited MECP2-containing duplication: autism and intellectual disability, but not seizures or respiratory infections. BMC Med Genet. 2012;13:75.CrossRefPubMedCentralPubMedGoogle Scholar
  44. 44.
    Yang T, Ramocki MB, Neul JL, Lu W, Roberts L, Knight J, et al. Overexpression of methyl-CpG binding protein 2 impairs T(H)1 responses. Sci Transl Med. 2012;5:4(163).Google Scholar
  45. 45.
    Shimada S, Okamoto N, Hirasawa K, Yoshii K, Tani Y, Sugawara M, et al. Clinical manifestations of Xq28 functional disomy involving MECP2 in one female and two male patients. Am J Med Genet A. 2013;161A(7):1779–85.CrossRefPubMedGoogle Scholar
  46. 46.
    Wax JR, Pinette MG, Smith R, Chard R, Cartin A. Second-trimester prenasal and prefrontal skin thickening - association with MECP2 triplication syndrome. J Clin Ultrasound. 2013;41(7):434–7.CrossRefPubMedGoogle Scholar
  47. 47.
    Peters SU, Hundley RJ, Wilson AK, Carvalho CM, Lupski JR, Ramocki MB. Brief report: regression timing and associated features in MECP2 duplication syndrome. J Autism Dev Disord. 2013;43(10):2484–90.CrossRefPubMedGoogle Scholar
  48. 48.
    Novara F, Simonati A, Sicca F, Battini R, Fiori S, Contaldo A, et al. MECP2 duplication phenotype in symptomatic females: report of three further cases. Mol Cytogenet. 2014;7(1):10.CrossRefPubMedCentralPubMedGoogle Scholar
  49. 49.
    Scott Schwoerer J, Laffin J, Haun J, Raca G, Friez MJ, Giampietro PF. MECP2 duplication: possible cause of severe phenotype in females. Am J Med Genet A. 2014;164A(4):1029–34.CrossRefPubMedGoogle Scholar
  50. 50.
    Fukushi D, Yamada K, Nomura N, Naiki M, Kimura R, Yamada Y, et al. Clinical characterization and identification of duplication breakpoints in a Japanese family with Xq28 duplication syndrome including MECP2. Am J Med Genet A. 2014;164A(4):924–33.CrossRefPubMedGoogle Scholar
  51. 51.
    Ramocki MB, Tavyev YJ, Peters SU. The MECP2 duplication syndrome. Am J Med Genet A. 2010;152A(5):1079–88.CrossRefPubMedCentralPubMedGoogle Scholar
  52. 52.
    Van Esch H. MECP2 duplication syndrome. Mol Syndromol. 2012;2(3–5):128–36.PubMedCentralPubMedGoogle Scholar
  53. 53.
    Tomás JM. The main Aeromonas pathogenic factors. ISRN Microbiol. 2012;2012:256261.CrossRefPubMedCentralPubMedGoogle Scholar
  54. 54.
    Gibson 3rd FC, Tzianabos AO, Onderdonk AB. The capsular polysaccharide complex of Bacteroides fragilis induces cytokine production from human and murine phagocytic cells. Infect Immun. 1996;64(3):1065–9.PubMedCentralPubMedGoogle Scholar
  55. 55.
    Kalka-Moll WM, Wang Y, Comstock LE, Gonzalez SE, Tzianabos AO, Kasper DL. Immunochemical and biological characterization of three capsular polysaccharides from a single Bacteroides fragilis strain. Infect Immun. 2001;69(4):2339–44.CrossRefPubMedCentralPubMedGoogle Scholar
  56. 56.
    Coyne MJ, Tzianabos AO, Mallory BC, Carey VJ, Kasper DL, Comstock LE. Polysaccharide biosynthesis locus required for virulence of Bacteroides fragilis. Infect Immun. 2001;69(7):4342–50.CrossRefPubMedCentralPubMedGoogle Scholar
  57. 57.
    Buttery J, Moxon ER. Capsulate bacteria and the lung. Br Med Bull. 2002;61:63–80.CrossRefPubMedGoogle Scholar
  58. 58.
    Bao G, Zhang Y, Du C, Chen Z, Li Y, Cao Z, Ma Y. Genome sequence of Klebsiella oxytoca M5al, a promising strain for nitrogen fixation and chemical production. Genome Announc. 2013; 1(1).Google Scholar
  59. 59.
    Llobet E, Tomás JM, Bengoechea JA. Capsule polysaccharide is a bacterial decoy for antimicrobial peptides. Microbiology. 2008;154(Pt 12):3877–86.CrossRefPubMedGoogle Scholar
  60. 60.
    Dumanski AJ, Hedelin H, Edin-Liljegren A, Beauchemin D, McLean RJ. Unique ability of the Proteus mirabilis capsule to enhance mineral growth in infectious urinary calculi. Infect Immun. 1994;62(7):2998–3003.PubMedCentralPubMedGoogle Scholar
  61. 61.
    Deretic V, Dikshit R, Konyecsni WM, Chakrabarty AM, Misra TK. The algR gene, which regulates mucoidy in Pseudomonas aeruginosa, belongs to a class of environmentally responsive genes. J Bacteriol. 1989;171(3):1278–83.PubMedCentralPubMedGoogle Scholar
  62. 62.
    O’Riordan K, Lee JC. Staphylococcus aureus capsular polysaccharides. Clin Microbiol Rev. 2004;17(1):218–34.CrossRefPubMedCentralPubMedGoogle Scholar
  63. 63.
    Coldren FM, Palavecino EL, Levi-Polyachenko NH, Wagner WD, Smith TL, Smith BP, et al. Encapsulated Staphylococcus aureus strains vary in adhesiveness assessed by atomic force microscopy. J Biomed Mater Res A. 2009;89(2):402–10.CrossRefPubMedGoogle Scholar
  64. 64.
    Spellberg B, Daum R. Development of a vaccine against Staphylococcus aureus. Semin Immunopathol. 2012;34(2):335–48.CrossRefPubMedCentralPubMedGoogle Scholar
  65. 65.
    Nanra JS, Buitrago SM, Crawford S, Ng J, Fink PS, Hawkins J, et al. Capsular polysaccharides are an important immune evasion mechanism for Staphylococcus aureus. Hum Vaccin Immunother. 2012;18:9(3).Google Scholar
  66. 66.
    Foster TJ. Immune evasion by staphylococci. Nat Rev Microbiol. 2005;3(12):948–58.CrossRefPubMedGoogle Scholar
  67. 67.
    McKenney D, Hübner J, Muller E, Wang Y, Goldmann DA, Pier GB. The ica locus of Staphylococcus epidermidis encodes production of the capsular polysaccharide/adhesin. Infect Immun. 1998;66(10):4711–20.PubMedCentralPubMedGoogle Scholar
  68. 68.
    Dinkla K, Sastalla I, Godehardt AW, Janze N, Chhatwal GS, Rohde M, et al. Upregulation of capsule enables Streptococcus pyogenes to evade immune recognition by antigen-specific antibodies directed to the G-related alpha2-macroglobulin-binding protein GRAB located on the bacterial surface. Microbes Infect. 2007;9(8):922–31.CrossRefPubMedGoogle Scholar
  69. 69.
    Stollerman GH, Dale JB. The importance of the group a streptococcus capsule in the pathogenesis of human infections: a historical perspective. Clin Infect Dis. 2008;46(7):1038–45.CrossRefPubMedGoogle Scholar
  70. 70.
    Kang SO, Wright JO, Tesorero RA, Lee H, Beall B, Cho KH. Thermoregulation of capsule production by Streptococcus pyogenes. PLoS One. 2012;7(5):e37367.CrossRefPubMedCentralPubMedGoogle Scholar
  71. 71.
    Zhang SY, Boisson-Dupuis S, Chapgier A, Yang K, Bustamante J, Puel A, et al. Inborn errors of interferon (IFN)-mediated immunity in humans: insights into the respective roles of IFN-alpha/beta, IFN-gamma, and IFN-lambda in host defense. Immunol Rev. 2008;226:29–40.CrossRefPubMedGoogle Scholar
  72. 72.
    de Beaucoudrey L, Samarina A, Bustamante J, Cobat A, Boisson-Dupuis S, Feinberg J, et al. Revisiting human IL-12Rβ1 deficiency: a survey of 141 patients from 30 countries. Medicine (Baltimore). 2010;89(6):381–402.CrossRefGoogle Scholar
  73. 73.
    Bogunovic D, Byun M, Durfee LA, Abhyankar A, Sanal O, Mansouri D, et al. Mycobacterial disease and impaired IFN-γ immunity in humans with inherited ISG15 deficiency. Science. 2012;337(6102):1684–8.CrossRefPubMedCentralPubMedGoogle Scholar
  74. 74.
    Parvaneh N, Casanova JL, Notarangelo LD, Conley ME. Primary immunodeficiencies: a rapidly evolving story. J Allergy Clin Immunol. 2013;131(2):314–23.CrossRefPubMedGoogle Scholar
  75. 75.
    Snapper CM, Paul WE. Interferon-gamma and B cell stimulatory factor-1 reciprocally regulate Ig isotype production. Science. 1987;236(4804):944–7.CrossRefPubMedGoogle Scholar
  76. 76.
    Snapper CM, McIntyre TM, Mandler R, Pecanha LM, Finkelman FD, Lees A, et al. Induction of IgG3 secretion by interferon gamma: a model for T cell-independent class switching in response to T cell-independent type 2 antigens. J Exp Med. 1992;175(5):1367–71.CrossRefPubMedGoogle Scholar
  77. 77.
    Gerth AJ, Lin L, Peng SL. T-bet regulates T-independent IgG2a class switching. Int Immunol. 2003;15(8):937–44.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Michael Bauer
    • 1
    • 25
    Email author
  • Uwe Kölsch
    • 2
  • Renate Krüger
    • 1
  • Nadine Unterwalder
    • 2
  • Karin Hameister
    • 3
  • Fabian Marc Kaiser
    • 4
  • Aglaia Vignoli
    • 5
  • Rainer Rossi
    • 6
  • Maria Pilar Botella
    • 7
  • Magdalena Budisteanu
    • 8
  • Monica Rosello
    • 9
  • Carmen Orellana
    • 9
  • Maria Isabel Tejada
    • 10
  • Sorina Mihaela Papuc
    • 11
  • Oliver Patat
    • 12
  • Sophie Julia
    • 12
  • Renaud Touraine
    • 13
  • Thusari Gomes
    • 14
  • Kirsten Wenner
    • 15
  • Xiu Xu
    • 16
  • Alexandra Afenjar
    • 17
  • Annick Toutain
    • 18
  • Nicole Philip
    • 19
  • Aleksandra Jezela-Stanek
    • 20
  • Ludwig Gortner
    • 14
  • Francisco Martinez
    • 9
  • Bernard Echenne
    • 21
  • Volker Wahn
    • 1
  • Christian Meisel
    • 2
  • Dagmar Wieczorek
    • 22
  • Salima El-Chehadeh
    • 23
  • Hilde Van Esch
    • 24
  • Horst von Bernuth
    • 1
    • 2
    • 25
    Email author
  1. 1.Pediatric Pneumology and ImmunologyCharité University MedicineBerlinGermany
  2. 2.Labor Berlin GmbH, Department of ImmunologyBerlinGermany
  3. 3.Pediatric Neurology and Social Medicine KönigsbornUnnaGermany
  4. 4.Department of Stem Cell Transplantation and Immunology, Children’s HospitalGoethe University HospitalFrankfurt am MainGermany
  5. 5.Epilepsy Center, San Paolo Hospital, Department of Health SciencesUniversity of MilanMilanItaly
  6. 6.Childrens’ Hospital Neukölln, Vivantes GmbHBerlinGermany
  7. 7.Pediatric NeurologyTxagorritxu HospitalVitoria-GasteizSpain
  8. 8.“Prof. Dr. Alexandru Obregia” Clinical Hospital of PsychiatryBucharestRomania
  9. 9.Department of Genetics and prenatal diagnosticsHospital Universitario La FeValènciaSpain
  10. 10.Molecular Genetics Laboratory, Genetics Service, BioCruces Health Research InstituteCruces University HospitalBarakaldoSpain
  11. 11.“Victor Babes” National Institute of PathologyBucharestRomania
  12. 12.Service de génétique médicaleCHU Toulouse - Hôpital PurpanToulouseFrance
  13. 13.Service de génétiqueCHU de Saint-EtienneSaint-EtienneFrance
  14. 14.Department of General Pediatrics and Neonatology, Faculty of MedicineUniversity Children’s Hospital of the SaarlandHomburg/SaarGermany
  15. 15.Children’s University Hospital and Outpatient ClinicHamburg EppendorfGermany
  16. 16.Department of Child HealthcareChildren’s Hospital of Fudan UniversityShanghaiChina
  17. 17.Département de génétiqueCHU Paris-GH La Pitié Salpêtrière Hôpital Pitié-SalpêtrièreParisFrance
  18. 18.Service de génétiqueCHRU de Tours Hôpital BretonneauToursFrance
  19. 19.Unité de génétique clinique, Département de génétique médicaleCHU de Marseille, Hôpital de la TimoneMarseilleFrance
  20. 20.Department of Medical GeneticsThe Children’s Memorial Health InstituteWarsawPoland
  21. 21.Pediatric NeurologyCHU MontpellierMontpellierFrance
  22. 22.Institute of Human GeneticsUniversity Hospital Essen, University of Duisburg-EssenEssenGermany
  23. 23.Centre de GenetiqueHopital d’EnfantsDijonFrance
  24. 24.Center for Human GeneticsUniversity Hospital Leuven, KU LeuvenLeuvenBelgium
  25. 25.Charité – Kinderklinik mit Schwerpunkt Pneumologie und ImmunologieBerlinGermany

Personalised recommendations