Wu Junlai, Wang Ling, Ming Bingxia, Cai Shaozhe, Dong Lingli
Department of Rheumatology and Immunology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030, Wuhan, China.
Clin Rheumatol. 2025 May 15. doi: 10.1007/s10067-025-07456-2.
Cytomegalovirus (CMV) is a common opportunistic pathogen that poses significant health risks to immunosuppressed individuals, including those with rheumatic diseases (RD). CMV infection in RD patients can exacerbate disease activity and complicate clinical outcomes, leading to increased morbidity and potentially poorer prognosis. Understanding the risk factors associated with CMV infection in RD patients is crucial for improving diagnosis, management, and treatment strategies.
This study is aimed at analyzing the potential associated risk factors for CMV infection in RD, constructing a prediction model to predict the risk of CMV infection in RD patients, and exploring the impact of CMV DNA load on prognosis and virus conversion of patients.
In this retrospective nested case-control study, 660 patients with RD who were hospitalized at Tongji Hospital from January 2017 to October 2023 were reviewed, of whom 146 were diagnosed with CMV infection during follow-up. Based on a 1:2 propensity score matching with sex, age, and disease type, 292 RD patients without CMV infection were included as controls. In addition, the CMV infection group was further divided into high and low DNA load groups based on the median CMV DNA load (1600 copies/mL). Multivariate logistic regression analysis was conducted to identify independent risk factors for CMV infection in RD patients. A nomogram prediction model was constructed and validated based on multivariate logistic regression results.
Symptoms such as fever and diarrhea were more common in patients with CMV infection. The proportion of peripheral blood lymphocyte (LYM) count, immunoglobulin (Ig) A, IgG, IgM, CD3CD4 T cells, CD3CD8 T cells, CD3CD19 B cells, CD3CD19 T cells, and helper T (Th)/suppressor T (Ts) ratio below the lower limit of normal (LLN) was significantly higher in the CMV infection group compared to the non-CMV infection group. Multivariate logistic regression analysis revealed that IgG < LLN, Th/Ts ratio < LLN, high-dose glucocorticoid (GC) treatment in the past month, and use of cyclophosphamide (CTX) were risk factors for CMV infection in RD patients. The nomogram model based on the aforementioned identified risk factors showed a good prediction performance of CMV infection, with an area under the curve (AUC) of 0.898 (95% CI 0.890 ~ 0.979). Additionally, the PGA score significantly decreased after treatment compared to the period of CMV infection. Finally, high CMV DNA load was tightly correlated with down-regulated immunological features and poorer prognosis.
This study revealed that low IgG levels, decreased Th/Ts ratio, high-dose GC treatment, and use of CTX have important effects on CMV infection. Prediction of CMV infection based on these factors may help guide the early intervention in the potential CMV infection, and high CMV DNA load may indicate a poorer prognosis in RD patients. Key Points • RD patients with CMV infection are more immunosuppressive and exhibit severer clinical features. • A novel nomogram can help identify the potential CMV infection in RD patients. • High CMV DNA load is tightly correlated with down-regulated immunological features and poorer prognosis.
巨细胞病毒（CMV）是一种常见的机会性病原体，对免疫抑制个体，包括风湿性疾病（RD）患者构成重大健康风险。RD患者的CMV感染可加剧疾病活动并使临床结局复杂化，导致发病率增加和潜在的较差预后。了解RD患者CMV感染的相关危险因素对于改善诊断、管理和治疗策略至关重要。
本研究旨在分析RD患者CMV感染的潜在相关危险因素，构建预测模型以预测RD患者CMV感染风险，并探讨CMV DNA载量对患者预后和病毒转化的影响。
在这项回顾性巢式病例对照研究中，对2017年1月至2023年10月在同济医院住院的660例RD患者进行了回顾，其中146例在随访期间被诊断为CMV感染。基于性别、年龄和疾病类型进行1:2倾向评分匹配，纳入292例无CMV感染的RD患者作为对照。此外，根据CMV DNA载量中位数（1600拷贝/mL）将CMV感染组进一步分为高DNA载量组和低DNA载量组。进行多因素logistic回归分析以确定RD患者CMV感染的独立危险因素。基于多因素logistic回归结果构建并验证列线图预测模型。
发热和腹泻等症状在CMV感染患者中更常见。与非CMV感染组相比，CMV感染组外周血淋巴细胞（LYM）计数、免疫球蛋白（Ig）A、IgG、IgM、CD3CD4 T细胞、CD3CD8 T细胞、CD3CD19 B细胞、CD3CD19 T细胞以及辅助性T（Th）/抑制性T（Ts）比值低于正常下限（LLN）的比例显著更高。多因素logistic回归分析显示，IgG < LLN、Th/Ts比值 < LLN、过去1个月内使用高剂量糖皮质激素（GC）治疗以及使用环磷酰胺（CTX）是RD患者CMV感染的危险因素。基于上述确定的危险因素的列线图模型对CMV感染具有良好的预测性能，曲线下面积（AUC）为0.898（95%CI 0.890～0.979）。此外，与CMV感染期相比，治疗后患者的医师全面评估（PGA）评分显著降低。最后，高CMV DNA载量与免疫特征下调和较差预后密切相关。
本研究表明，低IgG水平、Th/Ts比值降低、高剂量GC治疗以及使用CTX对CMV感染具有重要影响。基于这些因素预测CMV感染可能有助于指导对潜在CMV感染的早期干预，并且高CMV DNA载量可能表明RD患者预后较差。要点：• CMV感染的RD患者免疫抑制程度更高，临床特征更严重。• 一种新型列线图有助于识别RD患者潜在的CMV感染。• 高CMV DNA载量与免疫特征下调和较差预后密切相关。
