Marou Emmanouela, Liaskos Christos, Simopoulou Theodora, Efthymiou Georgios, Dardiotis Efthymios, Katsiari Christina, Scheper Thomas, Meyer Wolfgang, Hadjigeorgiou Georgios, Bogdanos Dimitrios P, Sakkas Lazaros I
Department of Rheumatology and Clinical Immunology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Viopolis, 40500, Larissa, Thessaly, Greece.
Cellular Immunotherapy and Molecular Immunodiagnostics, Biomedical Section, Centre for Research and Technology-Hellas (CERTH)-Institute for Research and Technology-Thessaly (IRETETH), 41222, Larissa, Greece.
Clin Rheumatol. 2017 Apr;36(4):863-869. doi: 10.1007/s10067-017-3553-5. Epub 2017 Jan 26.
The role of human cytomegalovirus (HCMV) has been postulated as a trigger of systemic sclerosis (SSc). The aim of the study was to assess the prevalence of antibodies against HCMV UL44 and UL57 antigens not tested in the past. Sixty SSc patients, 40 multiple sclerosis and 17 normal controls (NCs), all anti-HCMV positive, were tested by immunoblotting. Reactivity to HCMV antigens, expressed as arbitrary units (AUs), was assessed for correlation with clinical and immunological parameters, including types of SSc-related autoantibodies. Anti-UL44 and anti-UL57 HCMV antibodies were present in 3/60 (5%) and 58/60 (96.7%) SSc patients, respectively (p < 0.001). Anti-UL57 antibodies were present in 35/40 (87.5%) MS patients and 16/17 (94.1%) NCs (SSc vs MS, MS vs NC, p = ns). Strong (50-75 AU) and very strong (75-100 AU) anti-UL57 immunoreactivity was found in 24 (41.4%) and 22 (37.9%) SSc patients, respectively (p = ns). Dilution experiments showed anti-UL57 antibody persistence in up to 1/5000. Overall, there was no difference in the frequency or the magnitude of anti-UL57 immunoreactivity between diffuse cutaneous systemic sclerosis and limited cutaneous systemic sclerosis patients (96.67 vs 96.67%; 65.45 ± 20.19 vs 64.31 ± 21.11 AU, p > 0.05) but strong anti-UL57 reactivity were more frequent in SSc compared to NCs (p = 0.007). Anti-UL57 reactivity was not inhibited by SSc-specific autoantigens. Anti-UL57 seropositivity did not correlate with demographic, clinical or immunological features of SSc. Anti-HCMV UL57 antibodies are universally present in anti-HCMV-positive patients with SSc, while those against UL44 are rarely seen. Because anti-UL57 lack disease specificity and are not involved in cross-reactive responses, their immunopathogenetic potential is to be questioned.
人类巨细胞病毒（HCMV）被认为是系统性硬化症（SSc）的触发因素。本研究旨在评估针对过去未检测过的HCMV UL44和UL57抗原的抗体的流行率。通过免疫印迹法检测了60例SSc患者、40例多发性硬化症患者和17例正常对照（NC），所有患者抗HCMV均为阳性。以任意单位（AU）表示的对HCMV抗原的反应性，被评估与临床和免疫参数的相关性，包括SSc相关自身抗体的类型。抗UL44和抗UL57 HCMV抗体分别在3/60（5%）和58/60（96.7%）的SSc患者中出现（p<0.001）。抗UL57抗体在35/40（87.5%）的MS患者和16/17（94.1%）的NC中出现（SSc与MS、MS与NC比较，p=无显著性差异）。在24例（41.4%）和22例（37.9%）的SSc患者中分别发现强（50 - 75 AU）和非常强（75 - 100 AU）的抗UL57免疫反应性（p=无显著性差异）。稀释实验显示抗UL57抗体在高达1/5000的稀释度下仍持续存在。总体而言，弥漫性皮肤系统性硬化症和局限性皮肤系统性硬化症患者之间抗UL57免疫反应性的频率或强度没有差异（96.67%对96.67%；65.45±20.19对64.31±21.11 AU，p>0.05），但与NC相比，SSc患者中强抗UL57反应性更常见（p=0.007）。抗UL57反应性不受SSc特异性自身抗原的抑制。抗UL57血清阳性与SSc的人口统计学、临床或免疫特征无关。抗HCMV UL57抗体普遍存在于抗HCMV阳性的SSc患者中，而抗UL44抗体则很少见。由于抗UL57缺乏疾病特异性且不参与交叉反应，其免疫发病机制潜力值得质疑。
