Volume 01 • Number 01 • September 2014
Commentary
Review
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Transient hypogammaglobulinemia of infancy (THI) was first described as a distinct entity by Gitlin and Janeway in 1956. Although THI has been recognized for many years, and despite significant progress in understanding the molecular basis and identifying the genes involved in the pathogenesis of many other forms of humoral immunodeficiencies, not much is known about this specific entity. This article summarizes the definition of THI, possible etiologies, clinical manifestations, treatment, and prognosis.
Original Article
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Introduction: Genetic aberrations associated with combined immunodeficiency have been increasingly identified in the past two decades. Yet, there are still 30% of these patients with unidentified genetic cause. Methods: We employed whole genome sequencing to identify the genetic defect leading to combined immunodeficiency. Thymus, gut, and lung tissues were studied using hematoxylin and eosin staining as well as immunohistochemistry. Results: We identified 2 deleterious mutations in the TTC7A gene. Surprisingly, the patient did not have intestinal atresia but suffered repeated infections as well fatal pneumonitis. Dendriform lung ossification developed, which was unique to this case. The patient had typical presentation of combined immunodeficiency including profound lymphopenia, markedly reduced in-vitro response to mitogens, as well as low TRECS. Serum immunoglobulins were also markedly reduced. Conclusion: Mutations in the TTC7A gene can cause combined immunodeficiency with no intestinal atresia and predispose to lung ossification. Statement of novelty: TTC7A mutations can cause profound immunodeficiency without multiple intestinal atresia. We report here for the first time that this defect is associated with dendriform lung ossification.
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Introduction: For close to half a century immunoglobulin replacement therapy has been the main therapy for patients unable to produce functioning antibodies. To date, both subcutaneous (SC) and intravenous delivery methods have been successful at effectively and safely replacing immunoglobulin. Home intravenous and SC therapy programs have been established and have gained attention, but the true motivation and frequency of switching from traditional hospital-based treatment to these alternatives remains unknown. This study aims to determine the willingness of patients in Canada to switch to a home-based gammaglobulin treatment program by quantifying related experiences and preferences. Methods: A cohort of 169 patients in Ontario currently on hospital-based intravenous immunoglobulin (IVIG) replacement therapy (referral centers or community hospitals) were sent a 2.5 page survey consisting of 25 questions. Data were collected and statistically analyzed using Fisher, χ2, and McNemar tests, where P < 0.05 was considered statistically significant. Results: Ninety-one patients responded and most agreed to consider home therapy regardless of the administration route, based on recommendations from an immunologist (IVIG, P = 0.006; SC, P < 0.001). Patients preferred switching to home IVIG rather than to SC (P = 0.01), but their concerns regarding home healthcare costs were more prominent with IVIG (P = 0.01). The main concern with current intravenous therapy was the overall loss of time (P = 0.0001), whereas for home therapy it was the loss of supervision (P = 0.0009) and possible associated costs. Patients considered home treatment more convenient, as it is less time consuming (P = 0.01), and this was perceived as an improvement in quality of life (P = 0.001). It was considered less convenient because it may be unsafe and (or) more expensive. Conclusion: This survey demonstrates that home intravenous therapy maybe the preferred option for patients with antibody deficiency in Ontario, provided this decision was supported by a specialist in the field, secured supervision was available, and it was not associated with personal expenses. Statement of novelty: The first study to examine patient willingness to try a new route of gammaglobulin administration at home.
Novel Mutation
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Introduction: Presentation with severe autoimmune manifestations in early infancy is rare, especially when the gut is not involved. Methods: Lymphocyte phenotyping, determination of autoantibodies, and Sanger sequencing were employed to investigate this case. Results: A novel homozygous mutation in CD25 was identified in the patient who presented in the first weeks of life with insulin-dependent diabetes mellitus (IDDM) and subsequently developed autoimmune cytopenia and pulmonary hemorrhage. Conclusion: CD25 deficiency is present in the Gulf (Oman) and cases with early autoimmune manifestations should be tested for this possibility. Statement of novelty: A novel mutation in CD25 leads to an early presentation of IDDM and pulmonary hemorrhage.
Imaging
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Background: Hyper IgE syndrome (HIES) is a primary immunodeficiency with sporadic, autosomal dominant (STAT3 mutation) and autosomal recessive (DOCK8 and TYK2 mutations) inheritance patterns. HIES is characterized by recurrent Staphylococcus infections including lung infections, skin and visceral abcesses, pulmonary pneumatoceles, mucocutaneous candidiasis, and eczematous rash with associated elevated IgE. Patients with STAT3 mutations have additional features including connective tissue, skeletal, dental, and vascular abnormalities. Methods: This case series highlights the clinical presentation, radiographic findings, and immunologic investigations of 4 siblings with HIES caused by STAT3 mutation. Results: Our patients presented with infections including Staphylococcus aureus visceral abscesses, skin lesions, pneumonia with associated pneumatocele, and minimal signs of inflammation such as fever. Additional characteristic features included eczematous rash, scoliosis, fractures, and delayed shedding of primary teeth. Immune investigations were essentially unremarkable apart from elevated IgE and eosinophil counts. Detailed imaging identified infectious processes and associated noninfectious features of STAT3 mutations. Conclusion: Patients presenting with recurrent Staphylococcal cutaneous and visceral infections, pneumatoceles, candidiasis, and eczematous rash with associated elevated IgE should be investigated for STAT3 mutations. This case series highlights the important role of radiographic imaging to identify infectious processes as well as noninfectious associated features in patients with STAT3 mutations. Statement of novelty: Detailed images of morbidity associated with a STAT3 deficiency.
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