Schrijver Benjamin, Göpfert Jens, La Distia Nora Rina, Putera Ikhwanuliman, Nagtzaam Nicole M A N, Smits Te Nijenhuis Marja A W, van Rijswijk Angelique L C T, Ten Berge Josianne C E M, van Laar Jan A M, van Hagen P Martin, Dik Willem A
Laboratory Medical Immunology, Department of Immunology, Erasmus MC University Medical Center Rotterdam, the Netherlands.
Department of Applied Biomarkers and Immunoassays, NMI Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, Germany.
Heliyon. 2024 Aug 28;10(18):e37103. doi: 10.1016/j.heliyon.2024.e37103. eCollection 2024 Sep 30.
In this study, we measured serum interferon (IFN) levels and activity in patients with sarcoidosis and tuberculosis (TB) with and without uveitis. We aimed to understand the role of IFN in the pathophysiology of both conditions and explore its potential as a discriminating marker for these clinically similar diseases.
Sera from an Indonesian TB and a Dutch sarcoidosis cohort were used in the analysis. IFNα2 and IFNγ concentrations were measured using Simoa® and Luminex assays, respectively. Serum IFN activity was assessed by incubating THP-1 cells with patient serum and measuring IFN-stimulated gene transcription using qPCR. Anti-IFNα2 and IFNγ autoantibodies were detected via Luminex assay and tested for neutralizing capacity using a flow cytometry-based signal transducer and activator of transcription (STAT) 1 phosphorylation inhibition assay.
IFNα2 was detected in 74 % and 64 % of patients with sarcoidosis and pulmonary TB, respectively, while IFNγ was found in 78 % and 23 % of patients with sarcoidosis and TB, respectively. For uveitis cases specifically, IFNα2 was detected in 85 % of sarcoid uveitis (SU) and 33 % of tubercular uveitis (TBU) cases. Similarly, IFNγ was detected in 69 % of SU and 17 % of TBU cases. IFNγ serum concentrations were higher in sarcoidosis than that in TB patients ( < 0.0001). Focusing on patients with uveitis, SU showed increased IFNα2 ( = 0.004) and IFNγ ( < 0.002) serum concentrations compared to that in TBU. Notably, TBU displayed significantly reduced IFNα2 concentrations compared to that in healthy controls ( = 0.006). These results align with the increased interferon stimulated gene (ISG) transcriptional upregulation observed in THP-1 cells stimulated with serum from patients with sarcoidosis. Elevated levels of non-neutralizing anti-IFN autoantibodies were observed in patients with TB; however, these levels were similar to those observed in geographically matched healthy Indonesian controls.
Our results suggest decreased serum levels and activity of type I and II IFN in TB compared to those in sarcoidosis. This is indicative of distinct pathophysiological processes in these highly clinically similar diseases. We propose that the assessment of serum IFN levels and IFN activity has the potential to distinguish between sarcoidosis/SU and TB/TBU.
在本研究中，我们测量了患有和未患有葡萄膜炎的结节病和结核病（TB）患者的血清干扰素（IFN）水平及活性。我们旨在了解IFN在这两种疾病病理生理学中的作用，并探索其作为这些临床相似疾病鉴别标志物的潜力。
分析中使用了来自印度尼西亚结核病队列和荷兰结节病队列的血清。分别使用Simoa®和Luminex检测法测量IFNα2和IFNγ浓度。通过将THP-1细胞与患者血清孵育，并使用qPCR测量IFN刺激基因转录来评估血清IFN活性。通过Luminex检测法检测抗IFNα2和IFNγ自身抗体，并使用基于流式细胞术的信号转导和转录激活因子（STAT）1磷酸化抑制试验测试其中和能力。
结节病患者和肺结核患者中分别有74%和64%检测到IFNα2，而结节病患者和结核病患者中分别有78%和23%检测到IFNγ。具体对于葡萄膜炎病例，结节性葡萄膜炎（SU）病例中有85%检测到IFNα2，结核性葡萄膜炎（TBU）病例中有33%检测到。同样，SU病例中有69%检测到IFNγ，TBU病例中有17%检测到。结节病患者的IFNγ血清浓度高于结核病患者（<0.0001）。聚焦于葡萄膜炎患者，与TBU相比，SU的IFNα2（=0.004）和IFNγ（<0.002）血清浓度升高。值得注意的是，与健康对照相比，TBU的IFNα2浓度显著降低（=0.006）。这些结果与在用结节病患者血清刺激的THP-1细胞中观察到的干扰素刺激基因（ISG）转录上调增加一致。在结核病患者中观察到非中和性抗IFN自身抗体水平升高；然而，这些水平与在地理匹配的印度尼西亚健康对照中观察到的水平相似。
我们的结果表明，与结节病相比，结核病患者血清中I型和II型IFN的水平及活性降低。这表明这些临床高度相似疾病中存在不同的病理生理过程。我们提出，评估血清IFN水平和IFN活性有可能区分结节病/SU和TB/TBU。
