Abstract
The diagnosis of adult-onset immunodeficiency syndrome associated with neutralizing anti-interferon γ autoantibodies (AIGA) presents substantial challenges to clinicians and pathologists due to its nonspecific clinical presentation, absence of routine laboratory tests, and resemblance to certain lymphoma types, notably nodal T follicular helper cell lymphoma, angioimmunoblastic type (nTFHL-AI). Some patients undergo lymphadenectomy for histopathological examination to rule out lymphoma, even in the absence of a preceding clinical suspicion of AIGA. This study aimed to identify reliable methods to prevent misdiagnosis of AIGA in this scenario through a retrospective case–control analysis of clinical and pathological data, along with immune gene transcriptomes using the NanoString nCounter platform, to compare AIGA and nTFHL-AI. The investigation revealed a downregulation of the C-X-C motif chemokine ligand 9 (CXCL9) gene in AIGA, prompting an exploration of its diagnostic utility. Immunohistochemistry (IHC) targeting CXCL9 was performed on lymph node specimens to assess its potential as a diagnostic biomarker. The findings exhibited a significantly lower density of CXCL9-positive cells in AIGA compared to nTFHL-AI, displaying a high diagnostic accuracy of 92.3% sensitivity and 100% specificity. Furthermore, CXCL9 IHC demonstrated its ability to differentiate AIGA from various lymphomas sharing similar characteristics. In conclusion, CXCL9 IHC emerges as a robust biomarker for differentiating AIGA from nTFHL-AI and other similar conditions. This reliable diagnostic approach holds the potential to avert misdiagnosis of AIGA as lymphoma, providing timely and accurate diagnosis.
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Data availability
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
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Acknowledgements
We are grateful for the technical support provided by the Core Labs, Department of Medical Research, National Taiwan University Hospital.
Funding
This study was partially funded by the National Science and Technology Council (110–2314-B-002–247, 111–2320-B-002–023, 111–2314-B-002–145 and 112–2320-B-002–040) and National Taiwan University Cancer Center (NTUCCS-112–07).
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CTY and UIW did conception and design; CTY, WTH, HW, YHP, UIW, JTW, and WHS performed experiment and analysis; CLH did transcriptome analysis; CTY, UIW wrote the paper; YCC, SCC, UIW critical revised the paper.
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This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Research Ethics Committee of National Taiwan University Hospital (No. 201412163RIND, 202301141RIND).
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Yuan, CT., Huang, WT., Hsu, CL. et al. CXCL9 as a Reliable Biomarker for Discriminating Anti–IFN-γ-Autoantibody–Associated Lymphadenopathy that Mimics Lymphoma. J Clin Immunol 44, 35 (2024). https://doi.org/10.1007/s10875-023-01643-z
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DOI: https://doi.org/10.1007/s10875-023-01643-z