Department of Respiratory Medicine and Infectious Disease, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Asahimachi-dori, Niigata, Japan.
Department of Respiratory Medicine, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjyo, Chuo-ku, Kumamoto, Japan.
J Clin Immunol. 2020 Feb;40(2):399-405. doi: 10.1007/s10875-020-00762-1. Epub 2020 Feb 7.
In the past decade, the relationship between naturally occurring interferon-γ-neutralizing autoantibodies (IFNγ-Ab) and disseminated non-tuberculous mycobacteria (NTM) infection has been established. Furthermore, immune suppressive therapy aimed at the suppression of antibody production has shown efficacy as a supportive treatment. However, the nature of antibody behavior and antibody titer during the course of this disease, as well as the pathophysiological significance of IFNγ-Ab, has not yet been fully elucidated.
Thirteen Japanese subjects suffering from disseminated NTM (dNTM) infection with IFNγ-Ab were evaluated. The fluctuation of IFNγ-Ab titer and the neutralizing capacity against IFN-γ during the course of the disease were retrospectively analyzed. IFNγ-Ab titers in the sera were quantified using an enzyme-linked immunosorbent assay; neutralizing capacity was evaluated via flow cytometry.
Serum antibody titers were not constant during the treatment period and varied over the course of the disease. The antibody titer decreased when the disease was improved by anti-mycobacterial treatment (p < 0.01) and increased as the disease progressed (p < 0.05). Even after the antibody titer decreased, the neutralizing capacity against IFN-γ was maintained by individual sera.
Despite the improvement in the pathological condition via treatment, the patients' sera maintained neutralizing capacity against IFN-γ. Antibody titer fluctuated over the course of the disease and exhibited potential as a biomarker for judgment of the disease state.
在过去的十年中,已经确立了天然产生的干扰素-γ中和自身抗体(IFNγ-Ab)与播散性非结核分枝杆菌(NTM)感染之间的关系。此外,旨在抑制抗体产生的免疫抑制疗法已被证明是一种有效的支持性治疗方法。然而,在这种疾病过程中抗体行为和抗体滴度的性质以及 IFNγ-Ab 的病理生理意义尚未完全阐明。
评估了 13 名患有播散性 NTM(dNTM)感染和 IFNγ-Ab 的日本受试者。回顾性分析了疾病过程中 IFNγ-Ab 滴度和对 IFN-γ 的中和能力的波动。使用酶联免疫吸附试验定量检测血清中的 IFNγ-Ab 滴度;通过流式细胞术评估中和能力。
在治疗期间,血清抗体滴度不是恒定的,并且在疾病过程中发生变化。当抗分枝杆菌治疗改善疾病时,抗体滴度下降(p < 0.01),并且随着疾病进展而增加(p < 0.05)。即使抗体滴度下降,个体血清仍保持对 IFN-γ 的中和能力。
尽管通过治疗改善了病理状况,但患者的血清仍保持对 IFN-γ 的中和能力。抗体滴度在疾病过程中波动,具有作为判断疾病状态的生物标志物的潜力。