TY - JOUR
T1 - Immune Dysfunction in Children with CHARGE Syndrome
T2 - A Cross-Sectional Study
AU - Wong, Monica T. Y.
AU - Lambeck, Annechien J. A.
AU - van der Burg, Mirjam
AU - la Bastide-van Gemert, Sacha
AU - Hogendorf, Lianne A.
AU - van Ravenswaaij-Arts, Conny M. A.
AU - Scholvinck, Elisabeth H.
PY - 2015/11/6
Y1 - 2015/11/6
N2 - 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.
AB - 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.
KW - 22Q11.2 DELETION SYNDROME
KW - CONJUGATE-VACCINE
KW - PRIMARY IMMUNODEFICIENCY
KW - MULTIPLEX IMMUNOASSAY
KW - PHENOTYPIC SPECTRUM
KW - NON-IMMUNOLOGISTS
KW - CHD7 GENE
KW - DIPHTHERIA
KW - IMMUNIZATION
KW - UPDATE
U2 - 10.1371/journal.pone.0142350
DO - 10.1371/journal.pone.0142350
M3 - Article
C2 - 26544072
SN - 1932-6203
VL - 10
JO - PLoS ONE
JF - PLoS ONE
IS - 11
M1 - e0142350
ER -