Infectious and Immunologic Phenotype of MECP2 Duplication Syndrome

Autores de IIS La Fe

• Mónica Pilar Roselló Piera

  Autor

• Carmen Orellana Alonso

  Autor

• 

  Francisco Martínez Castellano

  Autor

Participantes ajenos a IIS La Fe

• Bauer M
• Kölsch U
• Krüger R
• Unterwalder N
• Hameister K
• Kaiser FM
• Vignoli A
• Rossi R
• Botella MP
• Budisteanu M
• Tejada MI
• Papuc SM
• Patat O
• Julia S
• Touraine R
• Gomes T
• Wenner K
• Xu X
• Afenjar A
• Toutain A
• Philip N
• Jezela-Stanek A
• Gortner L
• Echenne B
• Wahn V
• Meisel C
• Wieczorek D
• El-Chehadeh S
• Van Esch H
• von Bernuth H

Grupos

• Investigación Traslacional en Genética

  

  Leader

  Francisco Martínez Castellano

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 IgG(2)-deficiency was detected - in 4/21 patients accompanied by IgA-deficiency, 10/21 patients showed low antibody titers against pneumococci. Supra-normal IgG(1)-levels were detected in 11/21 patients and supra-normal IgG(3)-levels were seen in 8/21 patients - in 6 of the patients as combined elevation of IgG(1) and IgG(3). Three of the four patients with IgA/IgG(2)-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/IgG(2)-deficiency, low antibody titers against pneumococci and elevated acute-phase responses. So patients with MECP2 duplication syndrome and low IgA/IgG(2) 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