Infectious and Immunologic Phenotype of MECP2 Duplication Syndrome

• DOI: 10.1007/s10875-015-0129-5
• Publication Date: 2015-02-26T05:32:05Z
• Authors: Michael Bauer; 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...; Ludwig Gortner; Francisco Martinez; Bernard Echenne; Volker Wahn; Christian Meisel; Dagmar Wieczorek; Salima El-Chehadeh; Hilde Van Esch; Horst von Bernuth
• Keywords: Medical microbiology; MeCP2; Primary Immunodeficiency; Common Variable Immunodeficiency

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.