Evaluation of herpesvirus members on hospital admission in patients with systemic lupus erythematous shows higher frequency of Epstein-Barr virus and its associated renal dysfunction

Abstract Introduction: Members of the Herpesviridae family have been described in patients with systemic lupus erythematous (SLE), but the clinical impact on renal function is not well known. Methods: HSV1, HSV2, VZV, EBV, CMV, HHV-6, HHV-7, and HHV-8 were evaluated by molecular biology on admission in blood samples from 40 consecutive SLE patients hospitalized for lupus activity. Results: Patients were 90.0% female, 77.5% non-white, with average age of 32.7 ± 13.6 years. We found positivity for EBV (65.0%), CMV (30.0%), HSV-1 (30.0%), HHV-6 (12.5%), and HHV-7 (7.5%). For all viruses, age, SLEDAI, hematological tests, ferritin, LDH, C-reactive protein, and erythrocyte sedimentation rate (ESR) were not significant. However, EBV positivity was a significant factor for higher serum creatinine (3.0 ± 2.8 vs. 0.9 ± 0.8; P = 0.001) and urea (86 ± 51 vs. 50 ± 46; P = 0.03). Moreover, positive cases for EBV only or with combined co-infections (66.7%-CMV; 58.3%-HSV-1) or negative for EBV only were evaluated by Kruskal-Wallis test again showed statistical significance for serum creatinine and urea (both P ≤ 0.01), with posttest also showing statistical differences for renal dysfunction and EBV presence (alone or in combined co-infections). The presence of EBV viral load was also significant for nephrotic-range proteinuria, renal flare, and the need for hemodialysis. Conclusion: Members of the Herpeviridae family (mainly EBV, HSV-1 and CMV) are common on hospital admission of SLE patients, reaching 65% for EBV, which seems to be associated with renal dysfunction and could reflect a previous association or overlapping disease, which is not well understood.

引言：已有研究在系统性红斑狼疮（SLE）患者体内检出疱疹病毒科（Herpesviridae）成员，但此类病毒对肾功能的临床影响尚不明确。

方法：本研究针对40例因狼疮活动住院的连续收治SLE患者，于其入院时采集血液样本，采用分子生物学方法检测单纯疱疹病毒1型（HSV-1）、单纯疱疹病毒2型（HSV-2）、水痘带状疱疹病毒（VZV）、EB病毒（EBV）、巨细胞病毒（CMV）、人类疱疹病毒6型（HHV-6）、人类疱疹病毒7型（HHV-7）及人类疱疹病毒8型（HHV-8）。

结果：本研究纳入的患者中，女性占比90.0%，非白人占比77.5%，平均年龄为32.7±13.6岁。检出阳性的病毒及对应阳性率分别为：EB病毒65.0%、巨细胞病毒30.0%、单纯疱疹病毒1型30.0%、人类疱疹病毒6型12.5%及人类疱疹病毒7型7.5%。针对所有检出病毒类型，患者年龄、系统性红斑狼疮疾病活动指数（SLEDAI）、血液学检测指标、铁蛋白、乳酸脱氢酶（LDH）、C反应蛋白及红细胞沉降率（ESR）均未表现出显著统计学差异。然而，EB病毒阳性与更高的血清肌酐水平（3.0±2.8 vs 0.9±0.8；P=0.001）及尿素水平（86±51 vs 50±46；P=0.03）显著相关。此外，将仅EB病毒阳性、合并其他病毒感染（合并巨细胞病毒感染者占比66.7%，合并单纯疱疹病毒1型感染者占比58.3%）以及仅EB病毒阴性的病例组进行Kruskal-Wallis检验（Kruskal-Wallis test）分析，结果显示血清肌酐与尿素水平仍存在显著统计学差异（均P≤0.01）；事后检验亦表明，肾功能不全与EB病毒阳性（单独感染或合并感染）存在显著统计学差异。EB病毒载量阳性还与肾病范围蛋白尿、肾脏病情发作及血液透析需求显著相关。

结论：入院的SLE患者中，疱疹病毒科（Herpesviridae）成员检出率较高，以EB病毒、单纯疱疹病毒1型及巨细胞病毒为主，其中EB病毒检出率达65%。此类病毒感染似乎与肾功能不全相关，这可能反映了二者间潜在的关联或重叠发病机制，目前相关机制尚不明确。