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
Primary Immunodeficiency Care and Research Institute, Chang Gung Memory Hospital, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
J Clin Immunol. 2009 May;29(3):319-29. doi: 10.1007/s10875-008-9265-5. Epub 2008 Dec 13.
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.
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.
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.
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.
本研究旨在评估8年间未感染HIV的卡介苗诱发疾病（BCG-ID）儿童的免疫情况，特别关注基础疾病。
2000年至2007年期间纳入经临床病程、皮肤特征、病理学、特异性聚合酶链反应和/或基因分型证实患有BCG-ID的患者。研究淋巴细胞增殖、多形核细胞功能、白细胞介素（IL）-12/23-干扰素（IFN）-γ通路以及Toll样受体2相关信号传导。
在271,618例接种卡介苗的活产婴儿中，8例（7例男性）BCG-ID患者在8年期间入组，表现为3例播散型、2例远隔型和3例局部型BCG-ID。发病年龄为1至28个月。除1例CD3和自然杀伤细胞较低的患者外，所有患者均有疫苗接种疤痕，该患者经白细胞介素2受体共同γ链（IL2RG）突变（Arg226Lys）鉴定为严重联合免疫缺陷（SCID）。另1例新发IL2RG突变（Trp74Gly）的SCID患者感染更频繁。第3例原发性自身免疫性中性粒细胞减少症患者的播散型BCG-ID扩展至腹壁。第4例慢性黏膜皮肤念珠菌病患者有局部BCG-ID，对念珠菌和卡介苗抗原的淋巴细胞增殖受损。其余4例患者未检测到多形核细胞功能、IL-12/23-IFN-γ通路以及Toll样受体2相关信号传导的缺陷证据。
对未感染HIV的BCG-ID患者的免疫分析揭示了原发性免疫缺陷疾病，尤其是在我们队列中观察到的T细胞和中性粒细胞功能缺陷患者，包括原发性自身免疫性中性粒细胞减少症和慢性黏膜皮肤念珠菌病。
