Molecular Assessment of Staphylococcus Aureus Strains in STAT3 Hyper-IgE Syndrome Patients

Journal of Clinical Immunology - Hyper-IgE syndromes (HIES) are a group of inborn errors of immunity (IEI) caused by monogenic defects such as in the gene STAT3 (STAT3-HIES). Patients suffering...     

Coronary Artery Abnormalities in Hyper-IgE Syndrome

Objective

Hyper-IgE syndrome (HIES) is a rare primary immunodeficiency caused by autosomal dominant STAT3 mutations resulting in recurrent infections and connective tissue abnormalities. Coronary artery abnormalities have been reported infrequently. We aimed to determine the frequency and characteristics of coronary artery abnormalities.

Design

STAT3-mutated HIES patients (n?=?38), ranging in age from 8 to 57 years, underwent coronary artery imaging by computed tomography or magnetic resonance imaging. Images were evaluated for tortuosity, dilation, and aneurysm. Charts were reviewed for cardiac risk factors. To allow blinded image interpretation, an age- and gender-matched non-HIES group was also evaluated (n?=?33).

Results

Coronary artery tortuosity or dilation occurred in 70% of HIES patients, with aneurysms present in 37%, incidences much higher than in the literature and in our non-HIES group, in which 21% had tortuosity or dilation and 3% had aneurysms. Hypertension was more common in the HIES group than in the general population and was associated with vessel abnormalities. Atherosclerosis was uncommon and mild.

Conclusions

Coronary artery aneurysms and tortuosity are common in HIES, despite a paucity of atherosclerosis, suggesting that STAT3 plays an integral role in human vascular remodeling and atherosclerosis.     

Gastrointestinal Radiologic Manifestations of Proximal Spinal Muscular Atrophy (Kugelberg-Welander Syndrome)

Proximal spinal muscular atrophy (Kugelberg-Welander syndrome) is a degenerating disease of the anterior horn cells of the spinal cord with atrophy of the proximal muscles resembling muscular dystrophy. The patient in this report exhibits radiographic features in the gastrointestinal tract similar to those seen in the muscular dystrophies, including myotonic dystrophy.     

Lung Parenchyma Surgery in Autosomal Dominant Hyper-IgE Syndrome

Purpose

Autosomal dominant hyper-IgE syndrome (AD-HIES) due to heterozygous STAT3 mutation is a primary immunodeficiency characterized by eczema, elevated serum IgE, recurrent infections, and connective tissue and skeletal findings. Healing of pneumonias is often abnormal with formation of pneumatoceles and bronchiectasis. We aimed to explore whether healing after lung surgery is also aberrant.

Methods

We retrospectively analyzed the medical records of 32 patients with AD-HIES who received lung surgery for the management of pulmonary infections from 1960 to 2011. We collected information including patient demographics, STAT3 mutation status, clinical history, surgical and medical procedures performed, complications, related medical treatments, and outcomes.

Results

More than 50 % of lung surgeries had associated complications, with the majority being prolonged bronchopleural fistulae. These fistulae often led to empyemas that necessitated additional interventions including prolonged antibiotics, prolonged thoracostomy tube drainage and re-operations.

Conclusion

Lung surgery in AD-HIES patients is associated with high complication rates. STAT3 mutations likely lead to abnormalities in tissue remodelling that are further exacerbated by infection.     

Reduced Bone Density in Patients with Autosomal Dominant Hyper-IgE Syndrome

Background and Purpose

Autosomal dominant hyper-IgE syndrome (AD-HIES) is a rare primary immunodeficiency disorder . It has been recognized as a multisystem disorder and is characterized by both immunologic and non-immunologic manifestations. Possible bone involvement in autosomal dominant HIES include fractures, scoliosis, cystic bone changes, and osteopenia. We sought to evaluate the changes in bone density in adolescents and young adults with AD-HIES, mostly with proven STAT3 mutation, followed in our institute.

Methods

We studied eight patients with AD-HIES who attended our immunology clinic. All patients underwent at least one bone mass dual-energy x-ray absorptiometry assessment (dual-energy x-ray absorptiometry scan).These findings were evaluated.

Results

The age of the patients at the time of their first bone density scan ranged between 10 and 24 years (mean 16.1?±?4.0 years); the duration of follow-up was 4–11 years (mean 5.8?±?3.5 years). Four patients had a history of fractures. Mean Z score in these patients was ?1.8?±?0.7. For three patients, Z score was below ?1. The other four patients had no history of fractures. Mean Z score in these patients was ?0.9?±?0.5. Only one patient in this group had a Z score below ?1. Bone density was below average in all patients; mean spinal Z score was ?1.6?±?0.4. Four patients were followed through the second decade, and all showed progressive deterioration in bone density. Three were treated with alendronate sodium, with improvement in the bone scan results.

Conclusions

Bone density decreases considerably over time in adolescents and young adults suffering from AD- HIES. Treatment with alendronate sodium may be effective in alleviating osteopenia.     

Vertebral Aspergillosis in a Patient with Autosomal-Dominant Hyper-IgE Syndrome

We present a report of an autosomal-dominant hyper-IgE syndrome patient with vertebral aspergillosis. Early diagnosis and antifungal therapy with surgery are crucial for improving the outcome of this aggressive condition.     

Diffuse Large B Cell Lymphoma in Hyper-IgE Syndrome Due To <Emphasis Type="Italic">STAT3</Emphasis> Mutation

The Job or hyper-immunoglobulinemia E syndrome is a primary immunodeficiency that is usually inherited in an autosomal dominant fashion. With the discovery of mutations in the STAT3 gene in the majority of autosomal dominant cases, it is now possible to make a molecular diagnosis of hyper-IgE syndrome. Both primary and secondary immunodeficiencies, including hyper-IgE syndrome, may predispose for malignancies, especially lymphomas, mainly mature B cell lymphomas, and classical Hodgkin lymphoma. Here, we report of a 48-year-old male with hyper-IgE syndrome who developed a primary parotid gland diffuse large B cell lymphoma. Analysis for STAT3 mutations demonstrated that the causal mutation of hyper-IgE syndrome, R382Q, arose de novo in the patient and it was transmitted to three of his five children, all three of whom are clinically affected. We review the literature regarding lymphoma in hyper-IgE syndrome and the possible etiologic relationship with STAT3 mutations.     

Malignancy in STAT3 Deficient Hyper IgE Syndrome

Journal of Clinical Immunology -     

The Chronic Gastrointestinal Manifestations of Chagas Disease

Chagas disease is an infectious disease caused by the protozoan Trypanosoma cruzi. The disease mainly affects the nervous system, digestive system and heart. The objective of this review is to revise the literature and summarize the main chronic gastrointestinal manifestations of Chagas disease. The chronic gastrointestinal manifestations of Chagas disease are mainly a result of enteric nervous system impairment caused by T. cruzi infection. The anatomical locations most commonly described to be affected by Chagas disease are salivary glands, esophagus, lower esophageal sphincter, stomach, small intestine, colon, gallbladder and biliary tree. Chagas disease has also been studied in association with Helicobacter pylori infection, interstitial cells of Cajal and the incidence of gastrointestinal cancer.     

Correction to: Malignancy in STAT3 Deficient Hyper IgE Syndrome

Journal of Clinical Immunology -     

Hyper-IgE Syndrome due to an Elusive Novel Intronic Homozygous Variant in DOCK8

Journal of Clinical Immunology - Rare, biallelic loss-of-function mutations in DOCK8 result in a combined immune deficiency characterized by severe and recurrent cutaneous infections, eczema,...