title: Immunologic analysis of HIV-uninfected Taiwanese children with BCG-induced disease.
abstract: OBJECTIVE
  The aim of this study was to evaluate immunity in HIV-uninfected children with bacille Calmette-Guerin-induced disease (BCG-ID) over an 8-year period, with particular emphasis on underlying diseases.
  
  
  METHODS
  Patient afflicted with BCG-ID proven by clinical courses, dermatologic features, pathology, specific polymerase chain reaction, and/or spoligotyping were enrolled between 2000 and 2007. Lymphocyte proliferation, polymorphonuclear function, interleukin (IL)-12/23-interferons (IFN)-gamma circuit, and Toll-like receptor 2-associated signaling were investigated.
  
  
  RESULTS
  Of the 271,618 total live births who received the BCG vaccine, eight patients (seven males) with BCG-ID were enrolled during an 8-year period and presented as three disseminated, two distant, and three regional BCG-ID. Their age at onset ranged from 1 to 28 months. All had a vaccine-injection scar except for one with lower CD3 and natural killer cells, compatible with severe combined immunodeficiency (SCID) identified by IL-2 receptor common gamma chain (IL2RG) mutation (Arg226Lys). The other SCID patient with de novo IL2RG mutation (Trp74Gly) had more recurrent infections. The third patient with primary autoimmune neutropenia had disseminated BCG-ID extending to abdominal wall. The fourth patient with chronic mucocutaneous candidiasis had regional BCG-ID and impaired lymphocyte proliferation to Candida and BCG antigens. No defective evidence of polymorphonuclear functions, IL-12/23-IFN-gamma circuit, and Toll-like receptor 2-associated signaling was detected in the remaining four patients.
  
  
  CONCLUSIONS
  Immunologic analysis in HIV-uninfected patients with BCG-ID reveals primary immunodeficiency diseases, especially in those with deficiencies in T-cell and neutrophil functions observed in our cohort, including primary autoimmune neutropenia and chronic mucocutaneous candidiasis.
authors.affiliation: Primary Immunodeficiency Care and Research Institute, Chang Gung Memory Hospital, College of Medicine, Chang Gung University, Taoyuan, Taiwan. wen2707@hotmail.com
authors.forename: Wen-I
authors.initials: WI
authors.lastname: Lee
authors.forename: Fang-Chen
authors.initials: FC
authors.lastname: Liang
authors.forename: Jing-Long
authors.initials: JL
authors.lastname: Huang
authors.forename: Tang-Her
authors.initials: TH
authors.lastname: Jaing
authors.forename: Chi-Huei
authors.initials: CH
authors.lastname: Wang
authors.forename: Tzou-Yien
authors.initials: TY
authors.lastname: Lin
authors.forename: Yhu-Chering
authors.initials: YC
authors.lastname: Huang
authors.forename: Wei-Lun
authors.initials: WL
authors.lastname: Huang
authors.forename: Ruwen
authors.initials: R
authors.lastname: Jou
authors.forename: Meng-Ying
authors.initials: MY
authors.lastname: Hsieh
authors.forename: Ju-Hsin
authors.initials: JH
authors.lastname: Chia
authors.forename: Tsu-Lan
authors.initials: TL
authors.lastname: Wu
mesh_terms: D015551:Autoimmunity; D001500:BCG Vaccine / Q000008:administration & dosage / Q000009:adverse effects*; D002175:Candida / Q000276:immunology*; D002178:Candidiasis, Chronic Mucocutaneous / Q000175:diagnosis / Q000209:etiology / Q000276:immunology* / Q000503:physiopathology; D049109:Cell Proliferation; D015331:Cohort Studies; D016207:Cytokines / Q000378:metabolism; D003937:Diagnosis, Differential; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008213:Lymphocyte Activation; D008297:Male; D009154:Mutation; D009503:Neutropenia / Q000209:etiology; D009894:Opportunistic Infections / Q000175:diagnosis / Q000209:etiology / Q000276:immunology* / Q000503:physiopathology; D015375:Receptors, Interleukin-2 / Q000235:genetics; D016511:Severe Combined Immunodeficiency / Q000175:diagnosis / Q000209:etiology / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology; D013624:Taiwan; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D014376:Tuberculosis / Q000517:prevention & control*; D014611:Vaccination
chemical_list: D001500:BCG Vaccine; D016207:Cytokines; D015375:Receptors, Interleukin-2; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2