Infectious and Immunologic Phenotype of MECP2 Duplication Syndrome

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

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.