The Potential and Limits of Hematopoietic Stem Cell Transplantation for the Treatment of Autosomal Dominant Hyper-IgE Syndrome

Yanagimachi, Masakatsu; Ohya, Takashi; Yokosuka, Tomoko; Kajiwara, Ryosuke; Tanaka, Fumiko; Goto, Hiroaki; Takashima, Takehiro; Morio, Tomohiro; Yokota, Shumpei

doi:10.1007/s10875-016-0278-1

Cited by 38 publications

(33 citation statements)

References 15 publications

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“…Although earlier attempts at HSCT did not demonstrate long-term benefits in AD-HIES, 36,37 recent experiences have been more successful and are somewhat more encouraging. 17,38,39 This is the first study to report on quality of life in patients with AD-HIES revealing both depression and fatigue in a significant number, and associated with lung conditions. Because depression can lead to poor adherence to medical advice, 40 it would be important to screen patients for this and provide appropriate care.…”

Section: Discussionmentioning

confidence: 83%

Autosomal Dominant Hyper-IgE Syndrome in the USIDNET Registry

Gernez

Freeman

Holland

et al. 2018

The Journal of Allergy and Clinical Immunology: In Practice

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BACKGROUND Autosomal dominant hyper-IgE syndrome (AD-HIES) is a rare condition. OBJECTIVE Data from the USIDNET Registry provide a resource to examine the characteristics of patients with rare immune deficiency diseases. METHODS A query was submitted to the USIDNET requesting deidentified data for patients with physician-diagnosed AD-HIES through July 2016. RESULTS Data on 85 patients diagnosed with AD-HIES (50 males; 35 females) born between 1950 and 2013, collected by 14 physicians from 25 states and Quebec, were entered into the USIDNET Registry by July 2016. Cumulative follow-up was 2157 years. Of these patients, 45.9% had a family history of HIES. The complications reported included skin abscesses (74.4%), eczema (57.7%), retained primary teeth (41.4%), fractures (39%), scoliosis (34.1%), and cancer (7%). Reported allergic diseases included food (37.8%), environmental (18%), and drugs (42.7%). The mean serum IgE level was 8383.7 kU/mL and was inversely correlated to the patient’s age. A total of 49.4% had eosinophilia; 56% were known to be on trimethoprim-sulfamethoxazole, 26.6% on antifungal coverage, and 30.6% on immunoglobulin replacement therapy. Pneumonias were more commonly attributed to Staphylococcus aureus (55.3%) or Aspergillus fumigatus (22.4%); 19.5% had a history of lung abscess; these were most often associated with Pseudomonas aeruginosa (P Fisher’s exact test = .029) or A. fumigatus (P Fisher’s exact test = .016). Lung abscesses were significantly associated with drug reactions (P χ2 = .01; odds ratio: 4.03 [1.2–12.97]), depression (P Fisher’s exact test = .036), and lower Karnofsky index scores (P Mann-Whitney = .007). DISCUSSION Data from the USIDNET Registry summarize the currently reported clinical characteristics of a large cohort of subjects with AD-HIES.

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Section: Discussionmentioning

confidence: 83%

Autosomal Dominant Hyper-IgE Syndrome in the USIDNET Registry

Gernez

Freeman

Holland

et al. 2018

The Journal of Allergy and Clinical Immunology: In Practice

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“…Hematopoetic stem cell transplant, a treatment of choice in several primary immunodeficiencies, is of questionable benefit in STAT3‐HIES, likely due to extra‐hematopoietic alterations, and its inability to correct existing pulmonary complications. Lung surgery does not cure the underlying STAT3 defect, has a high rate of complications, reduces the total amount of functional lung tissue, and thus has a negative effect on the long‐term outcome .…”

Section: Discussionmentioning

confidence: 99%

“…Therapeutic options in STAT3‐HIES, such as hematopoetic stem cell transplant (HSCT), are of uncertain benefit . In particular, pulmonary complications such as pneumatoceles and bronchiectasis have been shown to persist after HSCT, though the frequency of pulmonary infections may be reduced . Lung transplantation has been reported for a single patient, who died due to pulmonary posttransplant Aspergillus fumigatus (A fumigatus) infection and transplant vasculopathy.…”

Section: Introductionmentioning

confidence: 99%

Lung disease in STAT3 hyper‐IgE syndrome requires intense therapy

Kröner

Neumann

Ley‐Zaporozhan

et al. 2019

Allergy

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Background: Pulmonary complications are responsible for high morbidity and mortality rates in patients with the rare immunodeficiency disorder STAT3 hyper-IgE syndrome (STAT3-HIES). The aim of this study was to expand knowledge about lung disease in STAT3-HIES.Methods: The course of pulmonary disease, radiological and histopathological interrelations, therapeutic management, and the outcome of 14 STAT3-HIES patients were assessed.

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“…Moreover, IL-22 is involved in clearance of skin infections and in b-defensin production by keratinocytes and lung epithelial cells [49]. Despite impairment of IL-22, signaling has not been proven in keratinocytes and epithelial cells of HIES patients, improvement of cutaneous manifestations after bone marrow transplantation suggests a prominent role of hematopoietic cells in skin defense of HIES patients [50].…”

Section: Stat3 Lof Heterozygous Mutations Results In Immune Dysregulatmentioning

confidence: 99%

STAT mutations as program switchers: turning primary immunodeficiencies into autoimmune diseases

Lorenzini

Dotta

Giacomelli

et al. 2016

Journal of Leukocyte Biology

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STAT proteins are a family of transcription factors that mediate cellular response to cytokines and growth factors. Study of patients with familial susceptibility to pathogens and/or autoimmune diseases has led to the identification of 7 inherited disorders that are caused by mutations of 4 STAT family genes. Homozygous or compound heterozygous mutations of STAT1 lead to complete or partial forms of STAT1 deficiency that are associated with susceptibility to intracellular pathogens and herpetic infections. Patients with heterozygous STAT1 gain-of-function (GOF) mutations usually present with chronic mucocutaneous candidiasis (CMC) but may also experience bacterial and viral infections, autoimmune manifestations, lymphopenia, cerebral aneurysms, and increased risk to develop tumors. STAT2 deficiency has been described in 5 family members and is characterized by selective susceptibility to viral infections, whereas STAT3 loss-of-function (LOF) mutations are causative of the autosomal-dominant hyper-IgE syndrome (HIES), a condition that is characterized by cutaneous and respiratory infections in association with mucocutaneous candidiasis, eczema, skeletal and connective tissue abnormalities, eosinophilia, and high levels IgE. STAT5B LOF and STAT3 GOF mutations are both associated with disorders characterized by autoimmune or allergic manifestations, together with increased risk of infections. Particularly, STAT5b deficiency results in growth hormone (GH) insensitivity, immunodeficiency, diarrhea, and generalized eczema, whereas STAT3 GOF mutations result in autoimmune cytopenia, lymphadenopathy, short stature, infections, enteropathy, and multiorgan autoimmunity, including early-onset type I diabetes, thyroiditis, hepatitis, arthritis, and interstitial lung disease.

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The Potential and Limits of Hematopoietic Stem Cell Transplantation for the Treatment of Autosomal Dominant Hyper-IgE Syndrome

Cited by 38 publications

References 15 publications

Autosomal Dominant Hyper-IgE Syndrome in the USIDNET Registry

Autosomal Dominant Hyper-IgE Syndrome in the USIDNET Registry

Lung disease in STAT3 hyper‐IgE syndrome requires intense therapy

STAT mutations as program switchers: turning primary immunodeficiencies into autoimmune diseases

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