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Immune Dysfunction in Children with CHARGE Syndrome: A Cross-Sectional Study.

Wong MT, Lambeck AJ, van der Burg M, la Bastide-van Gemert S, Hogendorf LA, van Ravenswaaij-Arts CM, Schölvinck EH - PLoS ONE (2015)

Bottom Line: All CHARGE patients had a history of infections (often frequent), mainly otitis media and pneumonia, leading to frequent use of antibiotics and to hospital admissions.Decreased T-cell numbers were found in 12 (50%) patients, presumably caused by insufficient thymic output since TREC amounts were also diminished in CHARGE patients.Based on our results, we recommend immunological evaluation of CHARGE patients with recurrent infections.

View Article: PubMed Central - PubMed

Affiliation: University of Groningen, University Medical Centre Groningen, Department of Genetics, Groningen, The Netherlands.

ABSTRACT
CHARGE syndrome is a variable, multiple congenital malformation syndrome. Patients with CHARGE syndrome have frequent infections that are presumed to be due to anatomical anomalies of the craniofacial region and upper airway, and cranial nerve problems resulting in swallowing difficulties and aspiration. The possible contribution of immunological abnormalities to these infections has not been systematically studied even though immune deficiencies have been described in patients with 22q11.2 deletion syndrome, a condition which shares remarkable clinical overlap with CHARGE syndrome. We assessed the frequency and nature of immune dysfunction in 24 children with genetically proven CHARGE syndrome. All patients, or their parents, completed a questionnaire on infectious history. Their immune system was extensively assessed through full blood counts, immunoglobulin levels, lymphocyte subpopulations, peripheral B- and T-cell differentiation, T-receptor excision circle (TREC) analysis, T-cell function, and vaccination responses. All CHARGE patients had a history of infections (often frequent), mainly otitis media and pneumonia, leading to frequent use of antibiotics and to hospital admissions. Decreased T-cell numbers were found in 12 (50%) patients, presumably caused by insufficient thymic output since TREC amounts were also diminished in CHARGE patients. Despite normal peripheral B-cell differentiation and immunoglobulin production in all patients, 83% of patients had insufficient antibody titers to one or more early childhood vaccinations. Based on our results, we recommend immunological evaluation of CHARGE patients with recurrent infections.

No MeSH data available.


Related in: MedlinePlus

IgM and IgG expression on memory B-cells.IgM and IgG expression on memory B-cells (CD27+IgD-) of a CHARGE patient (B, D) and a simultaneously analyzed healthy control (A, C). A, B) IgG and IgM expression are used to differentiate between class-switched memory B-cells (CD27+IgD-IgM-/CD27+IgD-IgG+) and IgM-only memory B-cells (CD27+IgD-IgG-IgM++). Memory B-cells with high IgM expression and no expression of IgG are considered to be IgM-only memory B-cells (upper-left quadrant), all other memory B-cells are considered to be class-switched memory B-cells. C, D) Part of the CHARGE patients show abnormal expression of IgM on class-switched memory B-cells compared to healthy controls. MFI, mean fluorescence intensity.
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pone.0142350.g001: IgM and IgG expression on memory B-cells.IgM and IgG expression on memory B-cells (CD27+IgD-) of a CHARGE patient (B, D) and a simultaneously analyzed healthy control (A, C). A, B) IgG and IgM expression are used to differentiate between class-switched memory B-cells (CD27+IgD-IgM-/CD27+IgD-IgG+) and IgM-only memory B-cells (CD27+IgD-IgG-IgM++). Memory B-cells with high IgM expression and no expression of IgG are considered to be IgM-only memory B-cells (upper-left quadrant), all other memory B-cells are considered to be class-switched memory B-cells. C, D) Part of the CHARGE patients show abnormal expression of IgM on class-switched memory B-cells compared to healthy controls. MFI, mean fluorescence intensity.

Mentions: Interestingly, in eight patients (33%), the memory B-cells, which clearly had undergone class-switch recombination as shown by strong IgG expression, retained IgM expression (Table 3 and Fig 1).


Immune Dysfunction in Children with CHARGE Syndrome: A Cross-Sectional Study.

Wong MT, Lambeck AJ, van der Burg M, la Bastide-van Gemert S, Hogendorf LA, van Ravenswaaij-Arts CM, Schölvinck EH - PLoS ONE (2015)

IgM and IgG expression on memory B-cells.IgM and IgG expression on memory B-cells (CD27+IgD-) of a CHARGE patient (B, D) and a simultaneously analyzed healthy control (A, C). A, B) IgG and IgM expression are used to differentiate between class-switched memory B-cells (CD27+IgD-IgM-/CD27+IgD-IgG+) and IgM-only memory B-cells (CD27+IgD-IgG-IgM++). Memory B-cells with high IgM expression and no expression of IgG are considered to be IgM-only memory B-cells (upper-left quadrant), all other memory B-cells are considered to be class-switched memory B-cells. C, D) Part of the CHARGE patients show abnormal expression of IgM on class-switched memory B-cells compared to healthy controls. MFI, mean fluorescence intensity.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4636349&req=5

pone.0142350.g001: IgM and IgG expression on memory B-cells.IgM and IgG expression on memory B-cells (CD27+IgD-) of a CHARGE patient (B, D) and a simultaneously analyzed healthy control (A, C). A, B) IgG and IgM expression are used to differentiate between class-switched memory B-cells (CD27+IgD-IgM-/CD27+IgD-IgG+) and IgM-only memory B-cells (CD27+IgD-IgG-IgM++). Memory B-cells with high IgM expression and no expression of IgG are considered to be IgM-only memory B-cells (upper-left quadrant), all other memory B-cells are considered to be class-switched memory B-cells. C, D) Part of the CHARGE patients show abnormal expression of IgM on class-switched memory B-cells compared to healthy controls. MFI, mean fluorescence intensity.
Mentions: Interestingly, in eight patients (33%), the memory B-cells, which clearly had undergone class-switch recombination as shown by strong IgG expression, retained IgM expression (Table 3 and Fig 1).

Bottom Line: All CHARGE patients had a history of infections (often frequent), mainly otitis media and pneumonia, leading to frequent use of antibiotics and to hospital admissions.Decreased T-cell numbers were found in 12 (50%) patients, presumably caused by insufficient thymic output since TREC amounts were also diminished in CHARGE patients.Based on our results, we recommend immunological evaluation of CHARGE patients with recurrent infections.

View Article: PubMed Central - PubMed

Affiliation: University of Groningen, University Medical Centre Groningen, Department of Genetics, Groningen, The Netherlands.

ABSTRACT
CHARGE syndrome is a variable, multiple congenital malformation syndrome. Patients with CHARGE syndrome have frequent infections that are presumed to be due to anatomical anomalies of the craniofacial region and upper airway, and cranial nerve problems resulting in swallowing difficulties and aspiration. The possible contribution of immunological abnormalities to these infections has not been systematically studied even though immune deficiencies have been described in patients with 22q11.2 deletion syndrome, a condition which shares remarkable clinical overlap with CHARGE syndrome. We assessed the frequency and nature of immune dysfunction in 24 children with genetically proven CHARGE syndrome. All patients, or their parents, completed a questionnaire on infectious history. Their immune system was extensively assessed through full blood counts, immunoglobulin levels, lymphocyte subpopulations, peripheral B- and T-cell differentiation, T-receptor excision circle (TREC) analysis, T-cell function, and vaccination responses. All CHARGE patients had a history of infections (often frequent), mainly otitis media and pneumonia, leading to frequent use of antibiotics and to hospital admissions. Decreased T-cell numbers were found in 12 (50%) patients, presumably caused by insufficient thymic output since TREC amounts were also diminished in CHARGE patients. Despite normal peripheral B-cell differentiation and immunoglobulin production in all patients, 83% of patients had insufficient antibody titers to one or more early childhood vaccinations. Based on our results, we recommend immunological evaluation of CHARGE patients with recurrent infections.

No MeSH data available.


Related in: MedlinePlus