X-linked carriers of chronic granulomatous disease: Illness, lyonization, and stability.
J Allergy Clin Immunol
; 141(1): 365-371, 2018 01.
Article
em En
| MEDLINE
| ID: mdl-28528201
ABSTRACT
BACKGROUND:
Chronic granulomatous disease (CGD) is characterized by recurrent life-threatening bacterial and fungal infections and aberrant inflammation. Mutations in CYBB cause X-linked CGD and account for 65% to 70% of cases in Western countries.OBJECTIVE:
We sought to understand the clinical manifestations associated with the X-linked CGD carrier state.METHODS:
We undertook a comprehensive retrospective study of 162 affected female subjects. We examined dihydrorhodamine 123 (DHR) oxidation data for percentage of X-chromosome inactivation. We correlated lyonization (%DHR+) with clinical features. Where possible, we followed %DHR+ values over time.RESULTS:
Clinical data were available for 93 femalesubjects:
%DHR+ values were 46% (mean) and 47% (median; SD, 24). Using the %DHR+ value as the criterion for X inactivation, 78% of patients had levels of inactivation of 20% to 80%, suggesting random inactivation that was independent of age. In contrast, carriers with CGD-type infections had median %DHR+ values of 8% (n = 14; range, 0.06% to 48%), and those with only autoimmune or inflammatory manifestations had median %DHR+ values of 39% (n = 31; range, 7.4% to 74%). Those with both infections and autoimmunity had low %DHR+ values (n = 6; range, 3% to 14%). A %DHR+ value of less than 10% was strongly associated with infections (odds ratio, 99). Strong association persisted when %DHR+ values were less than 20% (odds ratio, 12). Autoimmunity was not associated with %DHR+ values. In 2 sets of identical twins, the %DHR+ populations tracked closely over time. Although the %DHR+ populations were very similar between sisters, those between mothers and daughters were unrelated.CONCLUSIONS:
A low %DHR+ value strongly predicts infection risk in X-linked CGD carriers, and the carrier state itself is associated with autoimmunity.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fenótipo
/
Genes Ligados ao Cromossomo X
/
Estudos de Associação Genética
/
Doença Granulomatosa Crônica
/
Heterozigoto
Tipo de estudo:
Etiology_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Adolescent
/
Adult
/
Aged
/
Aged80
/
Child
/
Child, preschool
/
Female
/
Humans
/
Infant
/
Middle aged
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article