Infectious and Immunologic Phenotype of MECP2 Duplication Syndrome

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.

Electronic supplementary material

The online version of this article (doi:10.1007/s10875-015-0129-5) contains supplementary material, which is available to authorized users.