US study results show that the genetic abnormality underlying the pediatric condition methyl-CpG binding protein 2 (MECP2) duplication syndrome also causes immune dysfunction.
This, say David Corry (Baylor College of Medicine, Houston, Texas) and colleagues, provides an explanation for the high rates of recurrent infections, namely pneumonia, seen in children with the condition.
"Our findings confirm that when overexpressed in human and mouse T-helper (Th) cells, MECP2 selectively impairs cytokine interferon-γ (IFN-γ) secretion and Th type 1 (Th1) responses by acting as a transcriptional repressor and regulator of IFN-γ locus accessibility," add the authors.
Indeed, assessment of the medical records of 10 children with MECP2 duplication syndrome showed that all but one child suffered from recurrent respiratory tract infections.
Analysis of blood samples taken from these children revealed a high frequency of immune anomalies, such as mucosal inflammatory reactions and abnormal immunoglobulin (Ig) assay results.
Similar immune anomalies were also observed among a second group of 27 children with MECP2 duplication syndrome.
As reported in Science Translational Medicine, detailed immunotyping of lymphocytes obtained from blood samples taken from the group revealed a lack of the Th1 cells required to produce IFN-γ.
Corry et al say: "These findings indicate that children with duplication or triplication of the MECP2 gene have immune impairments related to their inability to mount robust Th1 responses, and suggest that the high frequency of pulmonary and other inflammatory complications affecting these children may be due to opportunistic pathogens."
Mouse model analyses revealed findings similar to those obtained from the two groups of children.
Specifically, mice genetically altered to overexpress MECP2 showed immune impairment and were unable to launch Th1cell-based immune responses when infected with the intra-macrophage parasite Leishmania major.
"The next step is to go back and aggressively figure out which pathogens are infecting these children and how best to treat them," concluded one of the study authors Melissa Ramocki, also from Baylor College of Medicine.
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