抗γ-干扰素自身抗体阳性耐多药结核病并发马尔尼菲等多重感染一例并文献复习

doi:10.19982/j.issn.1000-6621.20240212

摘要/Abstract

摘要：

目的: 报告1例抗γ-干扰素自身抗体阳性导致的耐多药结核病并发马尔尼菲等多重感染患者的诊治过程,并结合文献分析该病的临床特征、实验室检查、治疗及预后。方法: 回顾性分析2023年8月2日首都医科大学附属北京胸科医院收治的1例抗γ-干扰素自身抗体阳性导致的耐多药结核病并发马尔尼菲等多重感染患者的相关临床资料。检索截止时间2024年5月31日,分别从PubMed数据库中以“Anti-interferon-γ autoantibodies、Multidrug-resistant tuberculosis”同时为检索词,从万方数据库、中国知网以“抗γ-干扰素自身抗体、耐多药结核病”同时为检索词均未检索到相关文献。而以“抗γ-干扰素自身抗体、Anti-interferon-γ autoantibodies”分别为中英文关键词在万方数据库、中国知网和PubMed数据库进行检索,共检出抗γ-干扰素自身抗体并发药物敏感结核病2篇,检出抗γ-干扰素自身抗体并发机会性感染61篇,检出抗γ-干扰素自身抗体相关治疗17篇。总结该例患者特征并进行相关文献复习。结果: 该患者经过免疫评估,发现细胞免疫异常、基因突变,因药物不良反应和患者身体一般情况较差,错过最佳治疗时机,未达到理想效果。结合文献研究,65例并发两种及以上机会性感染,50例存在皮肤损害,而抗γ-干扰素自身抗体并发耐多药结核病患者既往无相关文献报道。文献报道中抗γ-干扰素自身抗体阳性的获得性免疫缺陷综合征患者中,机会性感染病原中马尔尼菲篮状菌病71例,非结核分枝杆菌病31例,结核病2例。其中,65例患者并发两种及以上机会性感染,50例患者存在皮肤损害。结论: 抗γ-干扰素自身抗体阳性患者可能合并多重感染,治疗效果差,尽早应用新型免疫制剂联合相关病原体治疗可能获得更好的预后。

关键词: 抗γ-干扰素自身抗体, 结核,抗多种药物性, 免疫疗法

Abstract:

Objective: To report the diagnosis and treatment of a case of multi-drug resistant tuberculosis complicated with multiple infections such as marneffei caused by positive anti interferon gamma auto-antibody, and analyzes the clinical characteristics, laboratory examination, treatment and prognosis of the disease combined with literature. Methods: The study retrospectively analyzed the clinical data of a case of multi-drug resistant tuberculosis complicated with multiple infections such as marneffei caused by positive anti interferon gamma auto-antibodies admitted to Beijing Chest Hospital affiliated to Capital Medical University on August 2, 2023. The search deadline is May 31, 2024. The relevant literature was not retrieved from PubMed database with “Anti interferon-γ auto-antibodies, Multi-drug resistant tuberculosis” as the search term, Wanfang database and CNKI database with “Anti-interferon-γ auto-antibodies, multi drug resistant tuberculosis” as the search term. However, “anti interferon gamma auto-antibodies and anti interferon gamma auto-antibodies” were detected in Wanfang database, CNKI and PubMed database respectively, and two anti interferon gamma auto-antibodies were detected with drug sensitive tuberculosis, 61 anti interferon gamma auto-antibodies were detected with opportunistic infection, and 17 anti-interferon-γ auto-antibodies were detected with related treatment. Summarize the patient’s characteristics and conduct relevant literature review. Results: After immune evaluation, the patient was found to have abnormal cellular immunity and gene mutations. Due to adverse drug reactions and poor general physical condition, the best treatment opportunity was missed and the desired effect was not achieved. According to literature research, 65 cases were complicated with two or more opportunistic infections, 50 cases had skin damage, and there was no previous literature report on anti-interferon-γ auto-antibodies complicated with multi-drug resistant tuberculosis. In the acquired immunodeficiency syndrome patients with positive anti-interferon-γ auto-antibodies reported in the literature, 71 cases of Marneffei’s basket shaped mycosis, 31 cases of non-tuberculous mycobacterial disease, and 2 cases of tuberculosis were opportunistic infection pathogens. Among them, 65 patients developed two or more opportunistic infections, and 50 patients had skin damage. Conclusion: Patients with positive anti-interferon-γ auto-antibodies may have multiple infections and poor treatment outcomes. Early use of new immune preparations combined with targeted treatment for related pathogens may achieve better prognosis.

Key words: Anti-interferon-γ auto-antibodies, Tuberculosis, multi-drug resistant, Immunotherapy

中图分类号:

田园, 荆玮, 王庆枫, 初乃惠, 聂文娟. 抗γ-干扰素自身抗体阳性耐多药结核病并发马尔尼菲等多重感染一例并文献复习[J]. 中国防痨杂志, 2024, 46(11): 1335-1342. doi: 10.19982/j.issn.1000-6621.20240212

Tian Yuan, Jing Wei, Wang Qingfeng, Chu Naihui, Nie Wenjuan. A case of multiple infections such as multidrug-resistant tuberculosis caused by positive anti-interferon-γ autoantibodies and literature review[J]. Chinese Journal of Antituberculosis, 2024, 46(11): 1335-1342. doi: 10.19982/j.issn.1000-6621.20240212

图/表 5

图1~4

图5~10

图11~13

表1

抗IFN-γ自身抗体阳性引起的不同病原体感染、相关治疗、功效评价

年份	第一作者及文献	疾病	治疗方案	给药剂量	功效评价
2014	Chetchotisakd 和Anunnatsiri^[17]	非结核分枝杆菌病(16例)	利奈唑胺,抗非结核分枝杆菌治疗方案	利奈唑胺600mg,1次/d,持续6周	低剂量的利奈唑胺对抗IFN-γ自身抗体有一定的抑制作用,同时对非结核分枝杆菌有较好的灭菌作用,但其有着显著的不良反应
2014	Czaja等^[14]	非结核分枝杆菌病(1例)	利妥昔单抗,甲基强的松龙,抗非结核分枝杆菌治疗方案	利妥昔单抗375mg/m²体表面积,4次/周;甲基强的松龙100mg,4次/周	治疗8个月后,抗IFN-γ自身抗体水平表现为持续抑制状态,而且降至初始水平的10%
2020	Laisuan等^[16]	非结核分枝杆菌病(17例)	环磷酰胺单独使用疗效与抗CD20+抗非结核分枝杆菌治疗方案	环磷酰胺每周平均剂量10.93mg/kg,1次/3周,每3周为1周期,总疗程5~13个周期。抗CD20 500mg/kg,总疗程2~6个周期	两者均有效降低了抗IFN-γ自身抗体水平,但环磷酰胺有避免不必要及长时间使用抗生素的能力
2021	Uno等^[15]	鸟分枝杆菌病(1例)	利妥昔单抗,环磷酰胺,泼尼松,抗鸟分枝杆菌治疗方案	单一使用泼尼松6个周期。联合使用利妥昔单抗375mg/m²,泼尼松50mg,环磷酰胺375mg/m²体表面积	单一使用泼尼松后抗IFN-γ抗体滴度减少,但停药后反复。联合应用利妥昔单抗+泼尼松+环磷酰胺后,抗IFN-γ抗体滴度逐渐减少,停药后无反复
2022	丘敏枝等^[13]	奴卡菌感染、马尔尼菲篮状菌病(1例)	利妥昔单抗,抗奴卡菌及抗非结核分枝杆菌治疗方案	利妥昔单抗600mg治疗(用法不详);利奈唑胺600mg,1次/d	抗IFN-γ抗体滴度下降,人信号传导子及转录激活子1 PI 10(STATI-PI10)越来越少,其中和作用越小
2021	谭洁等^[18]	哥伦比亚分枝杆菌病(1例)	丙种球蛋白注射液,甲强龙,抗非结核分枝杆菌治疗方案	丙种球蛋白注射液20g,1次/d,共7天;甲强龙40mg,1次/d,2周后减少甲强龙用药至20g,1次/d,逐渐减量停用	患者皮疹消退,破溃淋巴结愈合,肿大淋巴结缩小
2023	Angkasekwinai 等^[19]	各类机会性感染(5例)	硼替佐米+环磷酰胺,对比硼替佐米+利托西单抗,同时加用机会性感染抗菌方案	硼替佐米1.3mg/m²,每周1次,持续8周,然后环磷酰胺1mg·kg^-1·d^-1持续4个月,对比硼替佐米+利托西单抗	硼替佐米+环磷酰胺使用对抗IFN-γ抗体滴度水平无明显效果。硼替佐米+利托西单抗联合使用后,可降低IFN-γ抗体滴度水平

表1

表2

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突变类型	相关基因突变位点
SYK突变	chr9:90844287
C7、CREBBP杂合突变	STAT1-PI10
常染色体基因突变	IL12RB1,IL12B,SG15,IFNGR1,IFNGR2,STAT1,IRF8
X连锁MSMD	KBKG,CYBB