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

• Published in: Journal of clinical immunology 2011-04, Vol.31 (2), p.272-280
• Main Authors: Lee, Wen-I, Huang, Jing-Long, Lin, Shy-Jae, Yeh, Kuo-Wei, Chen, Li-Chen, Hsieh, Meng-Ying, Huang, Yhu-Chering, Kuo, Ho-Chang, Yang, Kunder D., Yu, Hong-Ren, Jaing, Tang-Her, Yang, Chih-Hsun
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Arteritis; Basal ganglia; Base Sequence; Biomedical and Life Sciences; Biomedicine; Brain injury; Bronchiectasis; c-Met protein; Child; Child, Preschool; Clinical aspects; Female; Gene Expression Regulation - immunology; Genetic analysis; Genetic diversity; Genotype & phenotype; Guanine Nucleotide Exchange Factors - genetics; Herpes simplex; Herpes simplex virus; Humans; Immunoglobulin E; Immunoglobulin Isotypes - blood; Immunoglobulins; Immunological memory; Immunology; Infant; Infections; Infectious Diseases; Internal Medicine; Job Syndrome - diagnosis; Job Syndrome - genetics; Job Syndrome - immunology; Job Syndrome - pathology; Lymphocytes B; Lymphocytes T; Lymphoma; Male; Medical Microbiology; Memory cells; Mollusca; Molluscum contagiosum; Molluscum Contagiosum - pathology; Mutation; Mutation - genetics; Myocardial infarction; Patients; Phenotype; Phenotypes; Primary immunodeficiencies; Protein-tyrosine kinase; Proteus mirabilis; Recurrent infection; Staphylococcus aureus; STAT3 Transcription Factor - genetics; Taiwan; Trauma; TYK2 Kinase - genetics; Vasculitis; Wound healing; Young Adult
• ISSN: 0271-9142; 1573-2592
• DOI: 10.1007/s10875-010-9479-1

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.