1 Research Institute for Health Sciences, 26682 Chiang Mai University , Chiang Mai 50202, Thailand.
2 Department of Internal Medicine, 26682 Chiang Mai University , Chiang Mai 50202, Thailand.
Exp Biol Med (Maywood). 2018 Apr;243(7):621-626. doi: 10.1177/1535370218764086. Epub 2018 Mar 7.
A major characteristic of immunodeficiency associated with life-threatening intracellular infection in adults is the presence of anti-interferon-γ antibodies. Although little is known about the mechanism underlying this syndrome, it is believed that the antibodies inhibit the activity of downstream signaling pathway of interferon-γ. In this study, the characteristics of these antibodies in patients who presented, or have a history of, intracellular infection and were positive to anti-interferon-γ antibodies were investigated. The antibodies exhibited mainly the IgG1 and the IgG4 subtypes and recognized the C-terminal of the interferon-γ linear epitope containing the KRKR motif, which is required for the biological activity of interferon-γ. The antibodies bound to recombinant interferon-γ with significantly lower avidity than antibodies to a recall antigen, tetanus toxoid, suggesting that the antibodies might have not undergone affinity maturation. The data from this study may provide fundamental information to better understand the properties of anti-interferon-γ antibodies, which can be useful for future studies. Impact statement An increase in the number of immunodeficient patients related to autoantibodies to interferon (IFN)-γ has been observed particularly in East Asian adults. These patients are often presented with opportunistic infections caused by intracellular pathogens, including non-tuberculous mycobacteria (NTM), Cryptococcus neoformans, Penicillium marneffei (now called Talaromyces marneffei), and non-typhoidal Salmonella spp. The mortality rate for this syndrome is relatively high with 32% patients dying at the median time of 25 months after diagnosis. Characterization of these autoantibodies may promote better understanding of the syndrome, an emerging health problem affecting East Asia populations and impeding their welfare and economic development.
成人致命性细胞内感染相关免疫缺陷的一个主要特征是存在抗干扰素-γ（IFN-γ）抗体。虽然人们对这种综合征的发病机制知之甚少，但据信这些抗体抑制了 IFN-γ下游信号通路的活性。在这项研究中，研究了在细胞内感染患者或有细胞内感染史且抗 IFN-γ抗体阳性的患者中这些抗体的特征。这些抗体主要表现为 IgG1 和 IgG4 亚型，识别 IFN-γ线性表位的 C 末端，该表位包含 KRKR 基序，是 IFN-γ生物活性所必需的。这些抗体与重组 IFN-γ的结合亲和力明显低于对回忆抗原破伤风类毒素的抗体亲和力，这表明这些抗体可能没有经历亲和力成熟。本研究的数据可为更好地了解抗 IFN-γ抗体的特性提供基础信息，这对未来的研究可能有用。
与 IFN-γ自身抗体相关的免疫缺陷患者数量的增加，尤其是在东亚成年人中，已经观察到。这些患者经常发生由细胞内病原体引起的机会性感染，包括非结核分枝杆菌（NTM）、新型隐球菌、彭氏假丝酵母（现在称为马尔尼菲青霉菌）和非伤寒沙门氏菌。该综合征的死亡率相对较高，中位数时间为 25 个月，32%的患者在诊断后死亡。这些自身抗体的特征描述可能会促进对该综合征的更好理解，该综合征是影响东亚人群的一个新兴健康问题，阻碍了他们的福利和经济发展。
