de Gruijl T D, Bontkes H J, Walboomers J M, Stukart M J, Robbesom A A, von Blomberg-van der Flier B M, Herbrink P, Remmink A J, Verheijen R H, Helmerhorst T J, Meijer C J, Scheper R J
Department of Pathology, Free University Hospital, Amsterdam, The Netherlands.
Int J Cancer. 1996 Dec 11;68(6):731-8. doi: 10.1002/(SICI)1097-0215(19961211)68:6<731::AID-IJC7>3.0.CO;2-4.
IgG reactivity against the immunodominant region aa6-35 of Human Papillomavirus (HPV) type-16 E7 was determined in a peptide-based ELISA in a cohort study of women with initial mild to moderate cervical dyskaryosis. On the basis of HPV DNA patterns, as determined by PCR in cervical smears prior to IgG testing, HPV-16-positive patients were grouped as having either a cleared, a fluctuating, or a persistent HPV-16 infection. In a cross-sectional study at the start of serological follow-up, positive IgG reactivities were found more often in the total group of HPV-16-positive patients (20.0%) than in patients consistently typed as HPV-negative over a period of at least 12 months prior to testing (3.1%, p < 0.04). The highest proportion of positive responders was found in patients with a cleared HPV-16 infection (29.4%). Also, IgG reactivities found in HPV-16 clearance patients were significantly higher than in patients with a persistent infection (p < 0.008). In a subsequent longitudinal study over a period of up to 27 months, consistently positive reactivities were observed in patients with cleared viral infections who showed seroreactivity in the cross-sectional study, while mostly negative reactivities were found in patients with viral persistence. HPV-16 E7-specific IgG subclass responses were determined in a selection of 19 CIN and 11 HPV-16-positive cervical carcinoma (CeCa) patients with positive E7-specific IgG responses. IgG2 was predominant in the CIN patients, suggesting the presence of IFNgamma (Th1) at the site of HPV infection. In the CeCa patients IgG1 and IgG2 were produced equally, possibly indicating a rise in Th2 cytokines. Our data suggest that HPV-16 E7 IgG reactivity in a subset of CIN patients with viral clearance may result from successful Th1 responses.
在一项针对初发为轻度至中度宫颈发育异常的女性队列研究中，通过基于肽段的酶联免疫吸附测定（ELISA）确定了针对人乳头瘤病毒16型（HPV-16）E7蛋白免疫显性区域aa6 - 35的IgG反应性。在进行IgG检测之前，通过对宫颈涂片进行聚合酶链反应（PCR）确定HPV DNA模式，将HPV-16阳性患者分为已清除、波动或持续感染HPV-16的组。在血清学随访开始时的一项横断面研究中，HPV-16阳性患者总群体中IgG反应阳性的比例（20.0%）高于在检测前至少12个月一直被判定为HPV阴性的患者（3.1%，p < 0.04）。在已清除HPV-16感染的患者中发现阳性反应者的比例最高（29.4%）。此外，在HPV-16清除患者中发现的IgG反应性显著高于持续感染患者（p < 0.008）。在随后长达27个月的纵向研究中，在横断面研究中显示有血清反应性的病毒感染已清除患者中观察到持续的阳性反应，而在病毒持续存在的患者中大多为阴性反应。在19例宫颈上皮内瘤变（CIN）患者和11例HPV-16阳性宫颈癌（CeCa）患者中，对E7特异性IgG反应阳性的患者进行了E7特异性IgG亚类反应的检测。在CIN患者中IgG2占主导，提示HPV感染部位存在干扰素γ（Th1）。在CeCa患者中，IgG1和IgG2的产生量相当，这可能表明Th2细胞因子增加。我们的数据表明，病毒清除的CIN患者亚组中HPV-16 E7 IgG反应性可能源于成功的Th1反应。
