Successful Haploidentical Donor Hematopoietic Stem Cell Transplant and Restoration of STAT3 Function in an Adolescent with Autosomal Dominant Hyper-IgE Syndrome

Patel, Niraj; Gallagher, Joel L.; Torgerson, Troy R.; Gilman, Andrew L.

doi:10.1007/s10875-015-0167-z

Cited by 32 publications

(25 citation statements)

References 39 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: 84%

“…One was transplanted for multiple reasons (autoimmune hemolytic anemia and persistent staphylococcus infections despite prophylaxis) and is alive and well off Ig and antibiotic prophylaxis. 17 Another patient, also alive, was transplanted for significant lung disease at a young age. One male patient did not return for his 6-month post-transplant follow-up.…”

Section: Resultsmentioning

confidence: 99%

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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: 84%

Section: Resultsmentioning

confidence: 99%

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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“…Bone marrow transplantation has been performed with mixed results and has thus far not been aggressively pursued for AD-HIES [65–69]. …”

Section: Germline Stat3 Loss-of-function: Hyper-ige Syndromementioning

confidence: 99%

The Ying and Yang of STAT3 in Human Disease

2015

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The transcription factor signal transducer and activator of transcription 3 (STAT3) is a critical regulator of multiple, diverse cellular processes. Heterozgyous, germline, loss-of-function mutations in STAT3 lead to the primary immune deficiency Hyper-IgE syndrome. Heterozygous, somatic, gain-of-function mutations in STAT3 have been reported in malignancy. Recently, germline, heterozygous mutations in STAT3 that confer a gain-of-function have been discovered and result in early-onset, multi-organ autoimmunity. This review summarizes what is known about the role of STAT3 in human disease.

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“…Several successful hematopoietic stem cell transplants (HSCT) in patients with AD-HIES have been published, prompting increased consideration of this option (47, 48). The immune defect corrects, but it is unclear how many of the somatic features will improve.…”

Section: Autosomal Dominant (Ad)-hies (Aka Job’s Syndrome)mentioning

confidence: 99%

Hyper-IgE Syndromes and the Lung

Freeman

Olivier

2016

Clinics in Chest Medicine

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Summary Elevated serum IgE has many etiologies including parasitic infection, allergy and asthma, malignancy and immune dysregulation. The hyper IgE syndromes due to mutations in STAT3, DOCK8 and PGM3 are monogenic primary immunodeficiencies that are associated with high IgE, eczema and recurrent infections. All of these primary immunodeficiencies are associated with recurrent pneumonias leading to bronchiectasis; however each has unique features and genetic diagnosis is essential in guiding therapy, discussing family planning and defining prognosis. STAT3 mutated HIES is unique with respect to its multi-organ features and frequent pneumatocele formation. DOCK8 deficiency is characterized by severe cutaneous viral infections and early mortality. PGM3 deficiency is newly defined and is distinct in having neurologic abnormalities and cytopenias.

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Successful Haploidentical Donor Hematopoietic Stem Cell Transplant and Restoration of STAT3 Function in an Adolescent with Autosomal Dominant Hyper-IgE Syndrome

Abstract: Haploidentical HSCT led to successful bone marrow engraftment, normalization of STAT3 signaling in hematopoietic cells, normalization of IgE, and restoration of immune function in this patient with AD-HIES.

Cited by 32 publications

References 39 publications

Autosomal Dominant Hyper-IgE Syndrome in the USIDNET Registry

Autosomal Dominant Hyper-IgE Syndrome in the USIDNET Registry

The Ying and Yang of STAT3 in Human Disease

Hyper-IgE Syndromes and the Lung

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