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Clinical Aspects and Genetic Analysis of Taiwanese Patients with the Phenotype of Hyper-Immunoglobulin E Recurrent Infection Syndromes (HIES)

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Abstract

Background

Hyper-immunoglobulin E recurrent infection syndromes (HIES) has characteristic features and identified mutations. This study investigated clinical features and causal candidate mutations in Taiwanese patients with the HIES phenotype on referral base over 23 million inhabitants.

Patients and Methods

Clinical manifestations of the HIES phenotype, severity scoring, immunological functions and candidate genes of signal transducer and activator of transcription 3 (STAT3), tyrosine kinase 2 (TYKZ), and dedicator of cytokineses 8 (DOCK8) were analyzed.

Results

Between 1985 and 2009, six sporadic and two siblings met HIES criteria (onset age: 2–54 months; severity score: 31–65) out of 187 patients with primary immunodeficiencies. Five patients with the autosomal dominant (AD)-HIES phenotype presented as pneumatocoele, bronchiectasis, retained primary teeth, minor trauma fracture, scoliosis, coronary aneurysm, and lymphoma. Three with the autosomal recessive (AR)-HIES phenotype and impaired lymphocyte proliferation function had herpes simplex virus infection, molluscum contagiosum, and cerebral vasculitis. Notably in one patient with the AR-HIES phenotype, unintentional lead component in traditional application herbs for accelerating wound healing deposited in basal ganglia and aggravated involuntary movement relative to cerebral vacculitis. Those with mildly elevated memory T cells and decreased memory B cells trended to develop arteritis. Of five AD-HIES patients, three were mortalities from acute myocardial infarction, Proteus mirabilis, and Staphylococcus aureus sepsis. Only one had de novo novel STAT3 (Gln 469 Arg) mutation with “relative” lower HIES STAT3 score.

Conclusions

Known genetic defects responsible for the HIES phenotype are not so common in Taiwan. This may infer genetic variations in different ethnicities although selection bias and under-diagnosis for HIES with known genetic defects could be contribution factors.

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Acknowledgments

The authors wish to thank all of the patients and their families for their kind cooperation, as well as their physicians for the referrals. This study was supported by the Chang Gung Medical Research Progress Grant CMRPG 490011 and the National Science Council (Grants NSC 99-2314-B-182-003-MY3 and NMRPD190315).

Conflict of interest

All of the authors declare no conflicts of interest.

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Authors and Affiliations

  1. Primary Immunodeficiency Care And Research (PICAR) Institute, Chang Gung Memorial Hospital and University College of Medicine, Taoyuan, Taiwan

    Wen-I Lee, Jing-Long Huang & Tang-Her Jaing

  2. Department of Pediatric Allergy, Immunology and Rheumatology, Chang Gung Memorial Hospital and University College of Medicine, Taoyuan, Taiwan

    Wen-I Lee, Jing-Long Huang, Shy-Jae Lin, Kuo-Wei Yeh & Li-Chen Chen

  3. Department of Pediatric Neurology, Chang Gung Memory Hospital and University College of Medicine, Taoyuan, Taiwan

    Meng-Ying Hsieh

  4. Graduate Institute of Medical Clinics, Chang Gung Memory Hospital and University College of Medicine, Taoyuan, Taiwan

    Meng-Ying Hsieh

  5. Department of Pediatric Infection, Chang Gung Memorial Hospital and University College of Medicine, Taoyuan, Taiwan

    Yhu-Chering Huang

  6. Department of Pediatric Hematology and Oncology, Chang Gung Memorial Hospital and University College of Medicine, Taoyuan, Taiwan

    Tang-Her Jaing

  7. Department of Pediatric Allergy, Immunology and Rheumatology, Chang Gung Memorial Hospital and University College of Medicine, Kaohsuing, Taiwan

    Ho-Chang Kuo, Kunder D. Yang & Hong-Ren Yu

  8. Department of Dermatology, Chang Gung Memorial Hospital and University College of Medicine, Taoyuan, Taiwan

    Chih-Hsun Yang

  9. Primary Immunodeficiency Care And Research (PICAR) Institute, Chang Gung Memory Hospital and University College of Medicine, #5 Fu-Shing St. (Pediatric Office 12 L), Kwei-Shan, Taoyuan, Taiwan

    Wen-I Lee & Chih-Hsun Yang

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  1. Wen-I Lee
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Correspondence to Wen-I Lee or Chih-Hsun Yang.

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Lee, WI., Huang, JL., Lin, SJ. et al. Clinical Aspects and Genetic Analysis of Taiwanese Patients with the Phenotype of Hyper-Immunoglobulin E Recurrent Infection Syndromes (HIES). J Clin Immunol 31, 272–280 (2011). https://doi.org/10.1007/s10875-010-9479-1

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  • DOI: https://doi.org/10.1007/s10875-010-9479-1

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