Clinical, Immunological and Molecular Characterization of DOCK8 and DOCK8-like Deficient Patients: Single Center Experience of Twenty Five Patients

Abstract

Autosomal recessive hyper-IgE syndrome is a combined immunodeficiency disease characterized by high morbidity and mortality rate. The different genetic background and environmental factors may explain the more severe phenotypes seen in our series. DOCK8 defect is the most common identified genetic cause. Patients with no identified genetic etiology are likely to carry mutations in the regulatory elements of genes tested or in novel genes that are yet to be discovered.

DOCK8 enforces immunological tolerance by promoting IL-2 signaling and immune synapse formation in Tregs

“…However, DOCK8-deficient patients only sporadically develop autoimmune disease (20,(23)(24)(25)(26). We report that mice with selective deficiency of DOCK8 in Tregs, but not Dock8 -/-mice, develop rampant autoimmunity, suggesting that deficient T effector cells (Teff) function may protect DOCK8-deficient patients from autoimmunity.…”

Cardiovascular abnormalities in primary immunodeficiency diseases

“…Similar vascular abnormalities including giant aortic aneurysm, brain infarction, and moya-moya syndrome were identified in patients with DOCK8 mutations (Alsum et al 2013). It is still not clear whether the vascular lesions are secondary to congenital angiogenesis defects post-infectious inflammation or to autoimmunity.…”

“…Pulmonary infections often result in pneumatoceles and (or) bronchiectasis. The autosomal recessive form (OMIM# 243700) is often associated with a more profound immunodeficiency resulting in susceptibility to viral infections, particularly papilloma and herpes viruses, autoimmunity, sclerosing cholangitis, and vasculitis (Heimall et al 2010;Alsum et al 2013).…”

Serum IgE Düzeyi ve Eozinofil Sayısı ile Atopik Hastalıklar Hiper IgE Sendromu’ndan Ayırt Edilebilir mi?

“…Ancak anaflaksi ve allerjik hastalık bildirilen olgular da literatürde mevcuttur (13,14). Bununla beraber DOCK8 gen defekti olan hastalarda inek sütü başta olmak üzere gıda allerjileri sık görülmektedir (15,16). Özellikle klinik bulguların henüz tam yerleşmediği küçük çocuklarda HİES yanlışlıkla gıda allerjisi, atopik dermatit tanıları alabilmektedir (17).…”