RESUMO
OBJECTIVE: Hyper-IgE syndrome (HIES) is a rare primary immunodeficiency caused by autosomal dominant STAT3 mutations resulting in recurrent infections and connective tissue abnormalities. Coronary artery abnormalities have been reported infrequently. We aimed to determine the frequency and characteristics of coronary artery abnormalities. DESIGN: STAT3-mutated HIES patients (n=38), ranging in age from 8 to 57 years, underwent coronary artery imaging by computed tomography or magnetic resonance imaging. Images were evaluated for tortuosity, dilation, and aneurysm. Charts were reviewed for cardiac risk factors. To allow blinded image interpretation, an age- and gender-matched non-HIES group was also evaluated (n=33). RESULTS: Coronary artery tortuosity or dilation occurred in 70% of HIES patients, with aneurysms present in 37%, incidences much higher than in the literature and in our non-HIES group, in which 21% had tortuosity or dilation and 3% had aneurysms. Hypertension was more common in the HIES group than in the general population and was associated with vessel abnormalities. Atherosclerosis was uncommon and mild. CONCLUSIONS: Coronary artery aneurysms and tortuosity are common in HIES, despite a paucity of atherosclerosis, suggesting that STAT3 plays an integral role in human vascular remodeling and atherosclerosis.
Assuntos
Aneurisma Coronário/patologia , Doença da Artéria Coronariana/patologia , Vasos Coronários/patologia , Hipertensão/patologia , Síndrome de Job/patologia , Fator de Transcrição STAT3 , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Estudos de Coortes , Aneurisma Coronário/complicações , Aneurisma Coronário/genética , Aneurisma Coronário/fisiopatologia , Angiografia Coronária , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/genética , Doença da Artéria Coronariana/fisiopatologia , Vasos Coronários/fisiopatologia , Feminino , Genes Dominantes , Humanos , Hipertensão/complicações , Hipertensão/genética , Hipertensão/fisiopatologia , Síndrome de Job/complicações , Síndrome de Job/genética , Síndrome de Job/fisiopatologia , Angiografia por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Mutação , Fator de Transcrição STAT3/genética , Tomografia Computadorizada por Raios XRESUMO
Hypomorphic mutations that lead to "leaky" severe combined immunodeficiency presentation with partial protein function are increasingly being identified. Mutations in recombination-activating genes (RAGs) 1 and 2 cause immunodeficiency and dysregulation ranging from severe combined immunodeficiency to Omenn syndrome to more mild immunodeficiencies. We report here the cases of 3 patients with hypomorphic RAG1 mutations with distinct presentations. One patient had granulomatous skin disease and disseminated nontuberculous mycobacteria; the second patient presented with predominantly autoimmune manifestations; and the third patient presented with relatively late onset of infections and had isolated T-cell lymphopenia. These disparate and atypical presentations of hypomorphic RAG1 mutations highlight the role of RAG1 in immune function and autoimmunity and expand the disease spectrum linked to these genes.
