Das Prabir, Minz Ranjana W, Saikia Biman, Sharma Aman, Anand Shashi, Singh Heera, Singh Surjit
Department of Immunopathology, 29751Post Graduate Institute of Medical Education and Research, Chandigarh, India.
Department of Internal Medicine, 29751Post Graduate Institute of Medical Education and Research, Chandigarh, India.
Lupus. 2022 Aug;31(9):1054-1066. doi: 10.1177/09612033221100156. Epub 2022 May 24.
Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease, which is known to be associated with HLA-DRB1 and Epstein-Barr virus (EBV) infection. In the Indian subcontinent where there is high seroendemicity of EBV, we postulated that the association of this virus in adult SLE (aSLE) and pediatric SLE (pSLE) patients would be different and differentially associate with the HLA-DRB1 susceptibility and protective genes.
A total of 109 aSLE, 52 pSLE, 215 adult healthy and 63 pediatric healthy controls were recruited. HLA-DRB1 genotyping by PCR-SSP, EBV load estimation by real-time PCR and antibody profiling (IgG & IgM) to EBV antigens by line blot assay were performed.
DRB115 was found predominant in pSLE patients and DRB103 in aSLE patients. DRB1*15/X heterozygous was predominant in overall SLE patients, although disease severity, like hypocomplementemia, higher autoantibody levels and more organ involvement was observed in *15/15 homozygous state. EBV strongly associated with pSLE patients showing higher percent of EA-D IgG ( < 0.0001) and p22 IgG ( = 0.035) along with higher viral load ( = 0.001) as compared to healthy controls. In addition, the higher EBV DNA load significantly associated with anti-EA-D IgG ( = 0.013) and DRB115/*15 ( = 0.007) in pSLE patients
This study therefore indicates that different HLA-DRB1 allotypes confer susceptibility to SLE in children and adults and disease may be triggered by increased EBV reactivation.
系统性红斑狼疮(SLE)是一种多系统自身免疫性疾病,已知与HLA - DRB1和爱泼斯坦 - 巴尔病毒(EBV)感染有关。在EBV血清流行率较高的印度次大陆,我们推测该病毒在成人SLE(aSLE)和儿童SLE(pSLE)患者中的关联会有所不同,并且与HLA - DRB1易感基因和保护基因存在差异关联。
共招募了109例aSLE患者、52例pSLE患者、215名成年健康对照者和63名儿童健康对照者。通过聚合酶链反应 - 序列特异性引物(PCR - SSP)进行HLA - DRB1基因分型,通过实时PCR进行EBV载量估计,并通过线性印迹法检测针对EBV抗原的抗体谱(IgG和IgM)。
发现DRB115在pSLE患者中占主导地位,而DRB103在aSLE患者中占主导地位。DRB115/X杂合子在总体SLE患者中占主导地位,尽管在15/15纯合状态下观察到疾病严重程度更高,如低补体血症、自身抗体水平升高和更多器官受累。与健康对照相比,EBV与pSLE患者密切相关,表现为EA - D IgG百分比更高(<0.0001)、p22 IgG更高(=0.035)以及病毒载量更高(=0.001)。此外,在pSLE患者中,较高的EBV DNA载量与抗EA - D IgG(=0.013)和DRB115/*15(=0.007)显著相关。
因此,本研究表明不同的HLA - DRB1同种异型赋予儿童和成人对SLE的易感性,并且疾病可能由EBV再激活增加引发。