Immunologic Analysis of HIV-Uninfected Taiwanese Children with BCG-Induced Disease

• Published in: Journal of clinical immunology 2009-05, Vol.29 (3), p.319-329
• Main Authors: Lee, Wen-I, Liang, Fang-Chen, Huang, Jing-Long, Jaing, Tang-Her, Wang, Chi-Huei, Lin, Tzou-Yien, Huang, Yhu-Chering, Huang, Wei-Lun, Jou, Ruwen, Hsieh, Meng-Ying, Chia, Ju-Hsin, Wu, Tsu-Lan
• Format: Article
• Language: English
• Subjects: Autoimmunity; Bacille Calmette-Guerin (BCG); BCG Vaccine - administration & dosage; BCG Vaccine - adverse effects; Biomedical and Life Sciences; Biomedicine; Candida; Candida - immunology; Candidiasis, Chronic Mucocutaneous - diagnosis; Candidiasis, Chronic Mucocutaneous - etiology; Candidiasis, Chronic Mucocutaneous - immunology; Candidiasis, Chronic Mucocutaneous - physiopathology; Cell Proliferation; chronic mucocutaneous candidiasis (CMC); Cohort Studies; Cytokines - secretion; Diagnosis, Differential; Follow-Up Studies; Human immunodeficiency virus; Humans; IL-2 receptor common gamma chain (IL2RG); Immunology; Infant; Infant, Newborn; Infectious Diseases; Internal Medicine; Lymphocyte Activation; Male; Medical Microbiology; Mutation; Neutropenia - etiology; Opportunistic Infections - diagnosis; Opportunistic Infections - etiology; Opportunistic Infections - immunology; Opportunistic Infections - physiopathology; primary autoimmune neutropenia (PAN); primary immunodeficiency diseases (PIDD); Receptors, Interleukin-2 - genetics; severe combined immunodeficiency (SCID); Severe Combined Immunodeficiency - diagnosis; Severe Combined Immunodeficiency - etiology; Severe Combined Immunodeficiency - genetics; Severe Combined Immunodeficiency - immunology; Severe Combined Immunodeficiency - physiopathology; Taiwan; Toll-Like Receptor 2 - metabolism; Tuberculosis - prevention & control; Vaccination
• ISSN: 0271-9142; 1573-2592
• DOI: 10.1007/s10875-008-9265-5

Objectives 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)-γ 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-γ circuit, and Toll-like receptor 2-associated signaling was detected in the remaining four patients. Conclusion 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.