Bortolotti Daria, Gentili Valentina, Bortoluzzi Alessandra, Govoni Marcello, Schiuma Giovanna, Beltrami Silvia, Rizzo Sabrina, Baldi Eleonora, Caselli Elisabetta, Pugliatti Maura, Castellazzi Massimiliano, Fernández Mercedes, Fainardi Enrico, Rizzo Roberta
Department of Chemical, Pharmaceutical and Agricultural Science, University of Ferrara, 44121 Ferrara, Italy.
Rheumatology Unit, Department of Medical Sciences, University of Ferrara and Azienda Ospedaliero-Universitaria S. Anna, 44124 Ferrara, Italy.
Microorganisms. 2022 Feb 23;10(3):494. doi: 10.3390/microorganisms10030494.
In multiple sclerosis (MS), there is a possible relationship with viral infection, evidenced by clinical evidence of an implication of infectious events with disease onset and/or relapse. The aim of this research is to study how human herpesvirus (HHVs) infections might dysregulate the innate immune system and impact autoimmune responses in MS. We analyzed 100 MS relapsing remitting patients, in the remission phase, 100 healthy controls and 100 subjects with other inflammatory neurological diseases (OIND) (neuro-lupus) for their immune response to HHV infection. We evaluated NK cell response, levels of HHVs DNA, IgG and pro- and anti-inflammatory cytokines. The results demonstrated that the presence of KIR2DL2 expression on NK cells increased the susceptibility of MS patients to HHV infections. We showed an increased susceptibility mainly to EBV and HHV-6 infections in MS patients carrying the KIR2DL2 receptor and HLA-C1 ligand. The highest HHV-6 viral load was observed in MS patients, with an increased percentage of subjects positive for IgG against HHV-6 in KIR2DL2-positive MS and OIND subjects compared to controls. MS and OIND patients showed the highest levels of IL-8, IL-12p70, IL-10 and TNF-alpha in comparison with control subjects. Interestingly, MS and OIND patients showed similar levels of IL-8, while MS patients presented higher IL-12p70, TNF-alpha and IL-10 levels in comparison with OIND patients. We can hypothesize that HHVs' reactivation, by inducing immune activation via also molecular mimicry, may have the ability to induce autoimmunity and cause tissue damage and consequent MS lesion development.
在多发性硬化症（MS）中，与病毒感染可能存在关联，这一点由感染事件与疾病发作和/或复发相关的临床证据所证实。本研究的目的是探讨人类疱疹病毒（HHV）感染如何可能导致先天性免疫系统失调，并影响MS中的自身免疫反应。我们分析了100例处于缓解期的复发缓解型MS患者、100例健康对照者以及100例患有其他炎症性神经系统疾病（OIND）（神经狼疮）的受试者对HHV感染的免疫反应。我们评估了自然杀伤（NK）细胞反应、HHV DNA水平、免疫球蛋白G（IgG）以及促炎和抗炎细胞因子。结果表明，NK细胞上KIR2DL2表达的存在增加了MS患者对HHV感染的易感性。我们发现，携带KIR2DL2受体和HLA - C1配体的MS患者主要对爱泼斯坦 - 巴尔病毒（EBV）和HHV - 6感染的易感性增加。在MS患者中观察到最高的HHV - 6病毒载量，与对照组相比，KIR2DL2阳性的MS和OIND受试者中抗HHV - 6 IgG阳性的受试者百分比增加。与对照受试者相比，MS和OIND患者的白细胞介素 - 8（IL - 8）、白细胞介素 - 12p70、白细胞介素 - 10和肿瘤坏死因子 - α（TNF - α）水平最高。有趣的是，MS和OIND患者的IL - 8水平相似，而与OIND患者相比，MS患者的IL - 12p70、TNF - α和IL - 10水平更高。我们可以推测，HHV的重新激活通过分子模拟等方式诱导免疫激活，可能具有诱导自身免疫并导致组织损伤以及随后MS病变发展的能力。
