Infectious and immunologic phenotype of MECP2 duplication syndrome

J Clin Immunol. 2015 Feb;35(2):168-81. doi: 10.1007/s10875-015-0129-5. Epub 2015 Feb 27.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute-Phase Proteins / metabolism
  • Adolescent
  • Adult
  • C-Reactive Protein / metabolism
  • Child
  • Child, Preschool
  • Cohort Studies
  • Female
  • Gene Duplication*
  • Genotype
  • Humans
  • Immunity, Cellular
  • Immunity, Humoral
  • Immunoglobulins / blood
  • Immunoglobulins / immunology
  • Infections / diagnosis
  • Infections / drug therapy
  • Infections / etiology*
  • Male
  • Mental Retardation, X-Linked / complications*
  • Mental Retardation, X-Linked / diagnosis
  • Mental Retardation, X-Linked / immunology*
  • Methyl-CpG-Binding Protein 2 / genetics*
  • Middle Aged
  • Phenotype*
  • Young Adult


  • Acute-Phase Proteins
  • Immunoglobulins
  • Methyl-CpG-Binding Protein 2
  • C-Reactive Protein

Supplementary concepts

  • Lubs X-linked mental retardation syndrome