背景:高滴度的干扰素(IFN)-γ自身抗体与细胞内病原体(如非结核分枝杆菌和马尔尼菲塔拉酵母)密切相关,但它们与结核分枝杆菌共同感染的马尔尼菲塔拉酵母并不常见。
方法:这里,我们报道了一例HIV阴性的中国男子,马尔尼菲塔拉酵母和结核分枝杆菌的播散性共感染,具有高滴度的抗IFN-γ自身抗体和CFI杂合子无义基因突变。患者迅速发展为败血症并死亡。通过流式细胞术检测CD4+T细胞的细胞内磷酸化STAT-1和Th1细胞(CD4+IFN-γ+细胞),我们发现,患者的血清可以抑制IFNγ诱导的CD4+T细胞\'STAT-1磷酸化和Th1细胞分化正常外周血单核细胞,但在正常对照血清中没有观察到这种现象。此外,培养基中血清浓度越高,对Th1细胞分化的抑制作用越明显。
结论:对于HIV阴性复发患者,耐火材料,致命的双重或多重细胞内病原体感染,尤其是马尔尼菲塔拉酵母,临床医生应该意识到,如果他们可能正在处理由于高滴度的抗IFN-γ自身抗体引起的成人发作的免疫缺陷综合征。还应进行系统的遗传和免疫学研究。
BACKGROUND: High-titer anti-interferon (IFN)-γ autoantibodies are strongly associated with intracellular pathogens such as nontuberculous mycobacteria and Talaromyces marneffei, but they are not as commonly associated with Talaromyces marneffei co-infected with Mycobacterium tuberculosis.
METHODS: Herein, we report a case of an HIV-negative Chinese man with a severe, disseminated co-infection of Talaromyces marneffei and Mycobacterium tuberculosis, who had a high-titer of anti IFN-γ autoantibodies and a CFI heterozygous nonsense gene mutation. The patient rapidly developed sepsis and died. Through by flow cytometry for CD4+ T cells\' intracellular phosphorylated STAT-1 and Th1 cells (CD4+ IFN-γ+ cells), we found that the patient\'s serum can inhibited IFN γ-induced CD4+ T cells\' STAT-1 phosphorylation and Th1 cell differentiation in normal peripheral blood mononuclear cells, but this phenomenon was not observed in normal control\'s serum. In addition, the higher serum concentration in the culture medium, the more obvious inhibition of Th1 cell differentiation.
CONCLUSIONS: For HIV-negative individuals with relapsing, refractory, fatal double or multiple intracellular pathogen infections, especially Talaromyces marneffei, clinicians should be aware that if they might be dealing with adult-onset immunodeficiency syndrome due to high-titer anti-IFN-γ autoantibodies. Systematic genetic and immunological investigations should also be performed.