抗中性粒细胞胞浆抗体相关性血管炎感染患者淋巴细胞及CD4^+T细胞减少与死亡的相关性

目的探讨使用激素和(或)环磷酰胺(cyclophosphamide,CTX)发生感染的抗中性粒细胞胞浆抗体(antineutrophil cytoplasmic antibody,ANCA)相关性血管炎(ANCA associated vasculitis,AAV)患者,住院期间淋巴细胞及CD4^+T细胞减少程度与死亡的相关性。方法回顾性分析2010至2013年北京协和医院治疗期间发生感染住院AAV患者的临床资料,按照淋巴细胞最低值连续两次符合≥0.8×10^9/L、0.5~0.79×10^9/L、0.3~0.49×10^9/L、<0.3×10^9/L分为无减少、轻度、中度和重度减少,CD4^+T细胞计数按照符合≥500×10^6/L、200~499×10^6/L、<200×10^6/L分为无减少、轻度和重度减少,并收集患者诊断、年龄、病程、住院时间、伯明翰系统性血管炎活动评分(BVAS)、CTX累计剂量、激素使用时间、感染部位和病原学,按转归分组行相关性及风险分析。结果共纳入67例患者,存活组与死亡组相比,年龄、病程、住院时间、BVAS、起病时肌酐水平及尿蛋白定量、CTX累计剂量、激素使用时间均无差异,淋巴细胞减少有统计学差异(P<0.001)。38例检测T细胞亚群,发现死亡组与存活组间CD4^+T细胞减少有统计学差异(P=0.003)。死亡组中,患者感染病原学以巨细胞病毒(cytomegalovirus,CMV)最常见,淋巴细胞重度下降组中最常见为鲍曼不动杆菌,其次分别为CMV、肺炎克雷伯菌、白色念珠菌;中度和轻度下降组最常见为CMV感染。多因素COX模型校正年龄和性别后的死亡风险预测分析发现,重度淋巴细胞减少HR为5.23(95%CI:1.68~16.31,P=0.004),中度下降HR为3.87(95%CI:1.03~14.54,P=0.045)。结论AAV患者感染后住院期间淋巴细胞及CD4^+T细胞减少与死亡相关,淋巴细胞中重度减少是死亡的风险因素,死亡患者主要感染病原体为CMV、鲍曼不动杆菌及肺炎克雷伯菌。

Association of lymphocytopenia and decrease of CD4+T cells with death in anti-neutrophil cytoplasmic antibody associated vasculitis patients with infections

Objective To investigate the association of lymphocytopenia and decrease of CD4^+T cells with death in anti-neutrophil cytoplasmic antibody associated vasculitis(AAV)patients with infections.Methods Sixty-seven AAV patients with infections who were admitted in Peking Union Medical College Hospital from 2010 to 2013 were recruited,and the clinical data were analyzed retrospectively.Lymphocytopenia was classified as no decrease,mild,moderate,or severe decrease according to the lowest count of lymphocytes which was consecutive twice consistent with that of≥0.8×10^9/L,0.5-0.79×10^9/L,0.3-0.49×10^9/L and<0.3×10^9/L.The T cell subset was classified as no decrease,mild,or severe decrease according to the lowest count of CD4 number which was consistent with that of≥500×10^6/L,200-499×10^6/L,and<200×10^6/L.The diagnosis,age,duration,hospitalization time,BVAS,cumulative dose of cyclophosphamide,duration of steroid use,site of infection,etiology and outcome of patients were collected.Association of lymphocytopenia and death was analyzed.Results No difference was found in age,duration,hospitalization time,BVAS,serum level of creatinine and urinary protein,cumulative dose of cyclophosphamide,duration of steroids use between the survival and death groups.Significant differences were found in the incidences of lymphocytopenia(P<0.001)and decrease of CD4^+T cell(P=0.003)between two groups.In death group,cytomegalovirus(CMV)was the leading etiology.Acinetobacter baumannii was the most common in patients with severe lymphocytopenia,followed by Klebsiella pneumoniae and Candida albicans.CMV was the most common in patients with moderate and mild lymphocytopenia.We found that the HR of severe lymphocytopenia was 5.23(95%CI:1.68-16.31,P=0.004),and HR of moderate lymphocytopenia was 3.87(95%CI:1.03-14.54,P=0.045)by multivariate COX model adjusted age and sex mortality risk prediction analysis.Conclusions Lymphocytopenia and decrease of CD4^+T cell of AAV patients with infections during hospitalization were associated with the risk of death.Moderate to severe lymphocytopenia was the risk factor of death.The common etiology of death among AAV patients with infections was CMV,Acinetobacter baumannii and Klebsiella pneumoniae.