Objectives

Early diagnosis of adult-onset immunodeficiency associated with neutralizing anti-interferon-gamma autoantibodies (anti-IFNγ Abs) remains difficult given the lack of a distinctive phenotype and a routine test. This study aimed to investigate the determinants of incorrect tentative diagnoses and useful clues for early disease recognition.

Methods

This study enrolled adult patients who had unexplained opportunistic infections diagnosed at six hospitals and identified those having neutralizing anti-IFNγ Abs (cases). Demographics, medical history, initial presentations and laboratory data, causative pathogens, tentative diagnoses, and treatment were analysed and compared among individuals having neutralizing anti-IFNγ Abs (cases) and those without (controls).

Results

Among the 154 patients enrolled, neutralizing anti-IFN-γ Abs were detected in 50 (71%) of 70 patients with disseminated non-tuberculous mycobacterial infection (dNTM) but not in 84 patients without dNTM. The median time from disease onset to the recognition of dNTM associated with neutralizing anti-IFNγ Abs was 1.6 years (range, 0.25–19 years). Incorrect tentative diagnoses resulted in the administration of anti-tuberculosis regimens (60%, 30/50), immunosuppressants (48%, 24/50), and systemic chemotherapy (2%, 10/50) to the 50 cases. Multivariate analysis revealed that case patients were more likely than controls to present with multiple bone lesions (adjusted odds ratio (OR), 27.16; 95% confidence interval (CI), 1.21–609.59) and leukocytosis (adjusted OR, 1.48; 95% CI, 1.12–1.95); however, the controls had a higher rate of mycobacterial bloodstream infection (adjusted OR, 0.05; 95% CI 0.00–0.66).

Conclusions

The high rate of incorrect tentative diagnoses led to frequent inappropriate management in patients with neutralizing anti-IFNγ Abs, and highlighted the need for increased awareness among clinicians.

中文翻译：

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中和性抗干扰素-γ-自身抗体患者的错误诊断。

目标

鉴于缺乏独特的表型和常规检测，与中和抗干扰素-γ自身抗体（抗IFNγAbs）相关的成人发作免疫缺陷的早期诊断仍然很困难。这项研究旨在调查错误的初步诊断的决定因素和早期疾病识别的有用线索。

方法

这项研究招募了在六家医院诊断为原因不明的机会感染的成年患者，并确定了具有中和性抗IFNγAbs的患者。分析并比较了具有中和性抗IFNγAbs的个体（病例）和没有中和性抗IFNγAbs的个体（病例）的人口统计学，病史，初步表现和实验室数据，致病性病原体，初步诊断和治疗。

结果

在纳入的154例患者中，在70例弥散性非结核分枝杆菌感染（dNTM）患者中，有50例（71％）检测到中和性抗IFN-γAbs，但在84例无dNTM的患者中未检出。从疾病发作到与中和性抗IFNγAbs相关的dNTM识别的中位时间为1.6年（范围0.25-19年）。不正确的初步诊断导致50例患者接受抗结核治疗方案（60％，30/50），免疫抑制剂（48％，24/50）和全身化疗（2％，10/50）。多因素分析显示，病例患者比对照组更容易出现多处骨病变（调整后的优势比（OR）为27.16； 95％置信区间（CI）为1.21-609.59）和白细胞增多症（调整后的OR为1.48； 95％CI ，1.12–1.95）；然而，

结论

暂定性诊断的不正确率很高，导致中和性抗IFNγAbs患者经常进行不适当的处理，并强调需要提高临床医生的认识。