Clinical, immunological and molecular findings of patients with DOCK‐8 deficiency from India

Background DOCK8 deficiency is an autosomal recessive form of combined immunodeficiency characterized by increased predisposition to allergy, autoimmunity and malignancies. Objective To analyze clinical, immunological, and molecular profiles of patients with DOCK8 deficiency. Methods Clinic records of all patients attending the primary immunodeficiency clinic from 2018 to 2021 were reviewed. Six patients from five families were found to have DOCK8 deficiency. Results Median age at diagnosis was 7.5 years (range: 2–13 years), with a male–female ratio of 5:1. Recurrent eczematous skin lesions were the predominant cutaneous manifestation present in 83% (5/6) of the patients. Warts and molluscum contagiosum were evident in 33% (2/6) and 16% (1/6) of the patients, respectively. Two patients had recalcitrant prurigo nodularis lesions and two had epidermodysplasia verruciformis (EV)-like lesions. Food allergies and asthma were reported by one patient each. Recurrent sinopulmonary infections were detected in 83% (5/6) of the patients. Epstein-Barr virus (EBV)-driven non-Hodgkin lymphoma with liver metastases was the only case of malignancy in a 4-year-old boy. IgE was elevated in all patients. Lymphopenia and eosinophilia were observed in 3/6 patients (50%) and 5/6 patients (83.3%), respectively. Genetic analysis showed homozygous deletion mutations in 2 patients, compound heterozygous deletion mutations in 1, and homozygous nonsense mutations in 2. A novel pathogenic homozygous missense variant in the DOCK8 gene was identified in one patient. Conclusions DOCK8 deficiency should be considered as a possibility in any patient with early onset eczema, cutaneous viral infections and increased predisposition to allergy, autoimmunity and malignancy.

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Viral infections and inborn errors of immunity

Ewing,

Madan

2024

Current Opinion in Infectious Diseases

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Purpose of review The purpose of this focused review is to discuss unusual presentations of viral infections in the context of specific inborn errors of immunity. We will discuss hyper immunoglobulin E (IgE) syndromes, epidermodysplasia verruciformis, and X-linked agammaglobulinemia as examples of inborn errors of immunity associated with specific presentations of viral infection and disease. Recent findings Advances in both genetic and viral diagnostics have broadened our understanding of viral pathogenesis in the setting of immune dysfunction and the variable phenotype of inborn errors of immunity. Dedicator of cytokinesis 8 (DOCK8) deficiency is now recognized as an inborn error of immunity within the hyper IgE syndrome phenotype and is associated with unusually aggressive cutaneous disease caused by herpes simplex and other viruses. Studies of patients with epidermodysplasia verruciformis have proven that rarely detected human papillomavirus subtypes may cause malignancy in the absence of adequate host defenses. Finally, patients with X-linked agammaglobulinemia may remain at risk for severe and chronic viral infections, even as immune globulin supplementation reduces the risk of bacterial infection. Summary Susceptibility to viral infections in patients with inborn errors of immunity is conferred by specific, molecular defects. Recurrent, severe, or otherwise unusual presentations of viral disease should prompt investigation for an underlying genetic defect.

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Clinical, immunological and molecular findings of patients with DOCK‐8 deficiency from India

Cited by 5 publications

References 22 publications

Emerging Spectrum of DOCK8 Deficiency in Children and Challenges Associated with Providing Treatment

Emerging Spectrum of DOCK8 Deficiency in Children and Challenges Associated with Providing Treatment

Clinical, immunological and molecular profiles of DOCK8 deficiency in six patients from a tertiary care centre in North India

Viral infections and inborn errors of immunity

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