Zainal Nurhafiza, Tan Kim-Kee, Johari Jefree, Hussein Heselynn, Wan Musa Wan Rosmaiza, Hassan Jamiyah, Lin Yee-Shin, AbuBakar Sazaly
Institute of Graduate Studies, University of Malaya, Kuala Lumpur, Malaysia.
Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
Microbiol Immunol. 2018 Oct;62(10):659-672. doi: 10.1111/1348-0421.12652.
Dengue is the most prevalent mosquito-borne disease in Southeast Asia, where the incidence of systemic lupus erythematosus (SLE) is approximately 30 to 53 per 100,000. Severe dengue, however, is rarely reported among individuals with SLE. Here, whether sera of patients with SLE cross-neutralize dengue virus (DENV) was investigated. Serum samples were obtained from individuals with SLE who were dengue IgG and IgM serology negative. Neutralization assays were performed against the three major DENV serotypes. Of the dengue serology negative sera of individuals with SLE, 60%, 61% and 52% of the sera at 1/320 dilution showed more than 50% inhibition against dengue type-1 virus (DENV-1), DENV-2 and DENV-3, respectively. The neutralizing capacity of the sera was significantly greater against DENV-1 (P < 0.001) and DENV-3 (P < 0.01) than against DENV-2 (P < 0.05). Neutralization against the DENV correlated with dengue-specific IgG serum titers below the cut-off point for dengue positivity. Depletion of total IgG from the sera of patients with SLE resulted in significant decreases of up to 80% in DENV inhibition, suggesting that IgG plays an important role. However, some of the SLE sera was still able to neutralize DENV, even with IgG titers <0.1 OD absorbance. Our findings suggest that sera of patients with SLE contain IgG, and possibly other type of antibodies, that can cross-neutralize DENV, which may explain the rarity of severe dengue in individuals with SLE. Further studies, are needed to further substantiate this finding and to elucidate the specific neutralizing epitopes recognized by the sera of individuals with SLE.
登革热是东南亚最普遍的蚊媒疾病,在该地区系统性红斑狼疮(SLE)的发病率约为每10万人中有30至53例。然而,严重登革热在SLE患者中很少有报道。在此,研究了SLE患者的血清是否能交叉中和登革病毒(DENV)。血清样本取自登革热IgG和IgM血清学检测呈阴性的SLE患者。针对三种主要的DENV血清型进行了中和试验。在登革热血清学检测呈阴性的SLE患者血清中,1/320稀释度的血清分别有60%、61%和52%对1型登革病毒(DENV-1)、DENV-2和DENV-3表现出超过50%的抑制作用。血清对DENV-1(P < 0.001)和DENV-3(P < 0.01)的中和能力显著强于对DENV-2的中和能力(P < 0.05)。对DENV的中和作用与低于登革热阳性临界值的登革热特异性IgG血清滴度相关。从SLE患者血清中去除总IgG导致DENV抑制作用显著降低高达80%,表明IgG起重要作用。然而,即使IgG滴度<0.1 OD吸光度,一些SLE血清仍能中和DENV。我们的研究结果表明,SLE患者的血清含有能够交叉中和DENV的IgG以及可能的其他类型抗体,这可能解释了SLE患者中严重登革热罕见的原因。需要进一步的研究来进一步证实这一发现,并阐明SLE患者血清所识别的特定中和表位。