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.
摘要：
由于其非特异性临床表现，与中和抗人干扰素γ自身抗体（AIGA）相关的成人发作性免疫缺陷综合征的诊断对临床医生和病理学家提出了重大挑战。没有常规的实验室检查，和某些类型的淋巴瘤相似，特别是结节性T滤泡辅助细胞淋巴瘤，血管免疫母细胞型（nTFHL-AI）。部分患者接受淋巴结清扫术进行组织病理学检查以排除淋巴瘤,即使之前没有AIGA的临床怀疑。本研究旨在通过对临床和病理资料的回顾性病例对照分析，找出可靠的方法来防止AIGA在这种情况下的误诊。以及使用NanoStringnCounter平台的免疫基因转录组，比较AIGA和nTFHL-AI。该研究揭示了AIGA中C-X-C基序趋化因子配体9（CXCL9）基因的下调，促使人们探索其诊断效用。对淋巴结标本进行靶向CXCL9的免疫组织化学(IHC)以评估其作为诊断生物标志物的潜力。结果显示，与nTFHL-AI相比，AIGA中CXCL9阳性细胞的密度显着降低。显示92.3%灵敏度和100%特异性的高诊断准确率。此外，CXCL9IHC证明了其区分AIGA与具有相似特征的各种淋巴瘤的能力。总之,CXCL9IHC作为用于区分AIGA与nTFHL-AI和其他类似病症的稳健生物标志物出现。这种可靠的诊断方法有可能避免将AIGA误诊为淋巴瘤。提供及时准确的诊断。
