Clinical aspects and genetic analysis of Taiwanese patients with the phenotype of hyper-immunoglobulin E recurrent infection syndromes (HIES).
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.


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.
Primary Immunodeficiency Care And Research Institute, Chang Gung Memorial Hospital and University College of Medicine, Taoyuan, Taiwan. wen2707@hotmail.com
Wen-I
WI
Lee
Jing-Long
JL
Huang
Shy-Jae
SJ
Lin
Kuo-Wei
KW
Yeh
Li-Chen
LC
Chen
Meng-Ying
MY
Hsieh
Yhu-Chering
YC
Huang
Ho-Chang
HC
Kuo
Kunder D
KD
Yang
Hong-Ren
HR
Yu
Tang-Her
TH
Jaing
Chih-Hsun
CH
Yang
D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics; D006801:Humans; D007132:Immunoglobulin Isotypes / Q000097:blood; D007223:Infant; D007589:Job Syndrome / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D008297:Male; D008976:Molluscum Contagiosum / Q000473:pathology; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D050796:STAT3 Transcription Factor / Q000235:genetics; D053634:TYK2 Kinase / Q000235:genetics; D013624:Taiwan; D055815:Young Adult
C516591:DOCK8 protein, human; D020662:Guanine Nucleotide Exchange Factors; D007132:Immunoglobulin Isotypes; D050796:STAT3 Transcription Factor; D053634:TYK2 Kinase