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Background Hyper-IgE syndromes (HIES) are distinct diseases characterized by recurrent cutaneous and lung infections, eczema, and elevated serum IgE level. Methods In this study, clinical manifestations, immunologic findings, and genetic studies of all patients with HIES in the Iranian national registry database were evaluated. Results A total of 129 HIES patients with a median age of 14.0 (9.0-24.0) years were followed up for a total of 307.8 patient-years. Genetic studies showed heterozygous STAT3 mutations in 19 patients and homozygous DOCK8 mutation in 16 patients. The mean of National Institutes of Health score in STAT3-deficient patients was higher than in patients with DOCK8 mutation (P = 0.001). It was shown that the presence of pneumatocele and hematologic complication were significantly frequent in STAT3-deficient cases compared to patients with DOCK8 deficiency (P = 0.001 and P = 0.002, respectively). Moreover, the median IgE serum levels were higher in patients with STAT3 gene mutation than in patients with DOCK8 gene mutation (P = 0.02). The eosinophils' count was enhanced in patients with DOCK8 deficiency than in patients with STAT3 gene defects (P = 0.02). Conclusion Specific molecular study of STAT3 and DOCK8 mutations in patients with HIES clinical phenotype could help the physician to definitively characterize the disease. Since HIES showed the highest rate of unsolved combined immunodeficiency, investigation of other genetic and environmental factors could also help in understanding the mechanism of remaining patients as well as providing strategy into therapeutic modalities.

Introduction Job's syndrome or hyper-immunoglobulin E syndromes (HIES) is a rare, heterogeneous complex of primary immunodeficiency disorders. It is characterized by triad of extremely high serum immunoglobulin E (IgE) levels, recurrent cutaneous infections like chronic eczematous dermatitis, skin abscesses and recurrent sinopulmonary infections. These patients have characteristic facial appearance and many oral manifestations. Eosinophilia, retention of deciduous teeth and skeletal abnormalities are other important clinical features of this syndrome. Familial HIES is of two types depending on the type of gene involved; autosomal-dominant HIES (AD-HIES), which develops due to mutation in human signal transducer and activator of transcription 3 gene (STAT3) and autosomal recessive HIES caused by DOCK8 gene mutation, but most cases are sporadic. Case presentation Hereby, we present a case of 5 years old female child who presented to our hospital with extensive eczematous lesions over flexural aspect of arms and over the gluteal region extending to the lower limb. The complete clinical presentation and lab investigations have confirmed AD-HIES syndrome. A novel missense mutation in exon 17 (c.1593A > T, p.K531 N) was identified in the STAT3 gene. Discussion The therapeutic strategy is directed mainly toward the prevention and management of infections and symptoms. Children affected with HIES can develop life-threatening pulmonary infections. Pulmonary complications must be identified in the early stage of the disease to treat them effectively. Hence, early diagnosis and proper management are necessary. Conclusion To date, information about paediatric HIES is limited. This case presents the clinical features, investigational procedures and management strategy for that particular condition in paediatric population., Highlights • Job’s syndrome is a rare, heterogeneous complex of primary immunodeficiency disorders. • It is characterized by triad of extremely high serum immunoglobulin E (IgE) levels, recurrent cutaneous infections and recurrent sinopulmonary infections. • Familial HIES is of two types; autosomal‑dominant HIES (AD‑HIES), which develops due to mutation in STAT3 gene and autosomal recessive HIES caused by DOCK8 gene mutation, but most cases are sporadic. • The therapeutic strategy is directed mainly toward the prevention and management of infections and symptoms.

AIMS/HYPOTHESIS: The LEW.1AR1-iddm rat, an animal model of human type 1 diabetes, arose through a spontaneous mutation within the inbred strain LEW.1AR1. A susceptibility locus (Iddm8) on rat chromosome 1 (RNO1) has been identified previously, which is accompanied by autoimmune diabetes and the additional phenotype of a variable CD3(+) T cell frequency. METHODS: In the present study we characterised the Iddm8 region on RNO1 in backcross strains using the genetically divergent Brown Norway (BN) and Paris (PAR) rats. Candidate genes of the Iddm8 region were sequenced for mutation analysis. RESULTS: The Iddm8 region could be subdivided by single nucleotide polymorphism (SNP) analyses. In the first region, a mutation in exon 44 of the Dock8 gene was identified resulting in an amino acid exchange in the protein from glutamine to glutamate. This exchange is unique for the LEW.1AR1-iddm rat. In the second region, a SNP was detected in exon 11 of the Vwa2 gene with an exchange from arginine to tryptophan. This SNP is also present in other rat strains. CONCLUSIONS/INTERPRETATION: The Dock8 mutation gave rise to a new type 1 diabetes rat model with very close similarity to type 1 diabetes in humans, providing a deepened insight into the impact of genes involved in diabetes development.

Job's syndrome or hyper-immunoglobulin E syndrome (HIES) is a heterogeneous complex of immunodeficiencies distinguishes by skin abscesses, recurrent pneumatoceles or staphylococcal infections, high serum immunoglobulin E levels and eczematous dermatitis. It has two types depends on type of gene involved; autosomal-dominant HIES (AD-HIES), which develops due to signal transducer and activator of transcription 3 gene and autosomal recessive HIES caused by DOCK8 gene mutation. Hereby we present a case of 13-month-old male child who admitted to our hospital with pustular lesions on the neck, face and upper chest associated with itching; some of these were hemorrhaged and crusted. The complete clinical presentation and lab investigations have confirmed AD-HIES syndrome. The therapeutic strategy was directed mainly toward the prevention and management of infections and symptoms. This case presents the clinical features, investigational procedures and management strategy for that particular condition in pediatrics.