Objective: To investigate the clinical characteristics of patients with acquired aplastic anemia (AA) accompanied by abnormal antinuclear antibody (ANA) and autoantibodies and their effects on the efficacy of immunosuppressive therapy (IST). Method: A retrospective case-control study was conducted, analyzing the clinical data of 291 patients with AA who underwent IST and were screened for autoantibodies at initial diagnosis between January 2018 and December 2019 at Blood Diseases Hospital, Chinese Academy of Medical Sciences. According to the titer of ANA at the initial diagnosis, extracted nuclear antigen antibodies (ENAs) abnormality and the change of ANA titer after treatment, the treatment responses of 3 months and 6 months after IST were compared. The correlation between clinical features and ANA abnormality was analyzed by univariate and multivariate logistic regression analysis. The parameters of univariate analysis P<0.1 were included in multivariate analysis, stepwise regression analysis and subgroup analysis. Results: A total of 291 patients were included in the study, of which 145 (49.83%) were male. Among all patients, 147 (50.52%) tested positive for ANA at initial diagnosis, with titers of 1∶100, 1∶320, and 1∶1 000 observed in 94, 47, and 6 cases, respectively. Female gender, older age, presence of paroxysmal nocturnal hemoglobinuria (PNH) clone, and higher levels of IgG, IgA, and thyroid hormone were significantly associated with ANA positivity at initial diagnosis, while white cell counts, reticulocytes, and free triiodothyronine were significantly lower than that of ANA-negatively patients (all P<0.05). Furthermore, logistic regression analyses revealed that female gender (OR=1.980, 95%CI 1.206-3.277), older age (OR=1.017, 95%CI 1.003-1.032), and presence of PNH clone (OR=1.875, 95%CI 1.049-3.408) were independent risk factors for ANA positivity at initial diagnosis. Subgroup analysis indicated that the risk of ANA positivity at initial diagnosis was even higher in PNH clone-positive patients in the subgroups of females (OR=1.24, 95%CI 1.02-1.51), severe AA (OR=1.26, 95%CI 1.07-1.47), and age≥40 years (OR=1.26, 95%CI 1.05-1.52) (all P<0.05). However, ANA titers at initial diagnosis, presence of other abnormal ENAs, and changes in ANA titers after treatment with IST were not correlated with treatment response (all P>0.05). Conclusions: Approximately 50% of patients with AA had abnormal ANA, and their presence was significantly associated with female gender, older age, and presence of PNH clone at initial diagnosis. However, the presence of abnormal ANA and changes in ANA titers after treatment did not affect the efficacy of IST in patients with AA.
目的： 探究伴抗核抗体（ANA）及自身抗体谱异常的再生障碍性贫血（AA）患者临床特点，以及其对免疫抑制治疗效果的影响。 方法： 回顾性病例对照研究。收集2018年1月至2019年12月于中国医学科学院血液病医院行免疫抑制治疗（IST）且初诊时行自身抗体筛查的291例AA患者的临床资料，对患者初诊时的临床特征进行分析，根据初诊时ANA滴度、是否伴有抗可溶性核抗原抗体（ENAs）异常及治疗后ANA滴度变化比较IST后3个月及6个月的治疗反应。初诊时临床特征与患者ANA异常相关性采用单因素和多因素logistic回归分析。单因素分析P<0.1的参数纳入多因素分析并进行逐步回归分析及亚组分析。 结果： 291例患者中男性145例（49.83%）。147例（50.52%）患者初诊ANA阳性，ANA滴度为1∶100、1∶320、1∶1 000者分别有94、47、6例。ANA阳性患者中女性比例、初诊时年龄、阵发性睡眠性血红蛋白尿症（PNH）克隆阳性比例、IgG、IgA、甲状腺素水平均显著高于ANA阴性组，白细胞计数、网织红细胞计数、游离三碘甲状腺原氨酸显著低于ANA阴性患者（均P<0.05），其他参数二者间差异均无统计学意义。单因素和多因素分析显示，女性（OR=1.980，95%CI 1.206~3.277）、年龄增加（OR=1.017，95%CI 1.003~1.032）、PNH克隆阳性（OR=1.875，95%CI=1.049~3.408）是初诊时ANA阳性的独立危险因素。亚组分析显示，在女性（OR=1.24，95%CI 1.02~1.51）、重型AA（OR=1.26，95%CI 1.07~1.47）、年龄≥40岁（OR=1.26，95%CI 1.05~1.52）的亚组中，PNH克隆阳性患者初诊时ANA阳性风险更大。初诊时ANA滴度、是否伴有ENAs异常及治疗后ANA滴度变化与IST治疗反应无相关性（P>0.05）。 结论： 约50%的AA患者伴有ANA异常，女性、高龄、伴有PNH克隆异常与初诊时ANA异常具有显著相关性。自身抗体谱异常及治疗后ANA滴度转归不影响AA患者的疗效。.