Bavinck J N, Gissmann L, Claas F H, Van der Woude F J, Persijn G G, Ter Schegget J, Vermeer B J, Jochmus I, Müller M, Steger G
Department of Dermatology, University Hospital, Leiden, The Netherlands.
J Immunol. 1993 Aug 1;151(3):1579-86.
Human papillomaviruses (HPV), especially the epidermodysplasia verruciformis (EV)-associated HPV 5, 8, 14, 17, 20, and 47, are thought to play a role in the pathogenesis of some skin cancers in recipients of renal allografts. MHC class I and class II genes are involved in the cellular immune response to viral and tumor Ag. Little is known about humoral responses to HPV in recipients with and without skin cancer. We investigated the prevalence of antibodies to the early (E) protein E7 and the major capsid late (L) protein L1 of HPV 8. In addition, we studied the association of HLA class II molecules with these antibody responses. The E7 and L1 open reading frames of HPV 8 were bacterially expressed as beta-galactosidase fusion proteins, which were purified by preparative gel electrophoresis. Serum samples from 36 renal transplant recipients with and 91 recipients without skin cancer were screened for the presence of IgG and IgM antibodies to HPV 8 E7 and L1, by Western blot analysis. The detection of anti-HPV 8 L1 antibodies represents the immune response to HPV 8 and possibly other EV-associated HPV, because cross-reactivity between the representatives of this HPV subgenus can occur. The antibody responses to HLA Ag were used as controls. Recipients who had IgM antibodies but no IgG antibodies to L1 of HPV 8 (patients with no apparent class switch from IgM to IgG) had skin cancer in 50% of cases, whereas recipients who produced IgG antibodies (patients with an apparently good humoral response to L1 of HPV 8) had skin cancer in only 18% of cases. The estimated relative risk of skin cancer in recipients with no class switch, compared with the risk in those with a good humoral response, was 4.5 (95% confidence interval, 1.1 to 18.1). We found no association between the antibody response to HLA Ag and the occurrence of skin cancer. A strong linkage between the absent class switch of antibody production in response to L1 of HPV 8 and HLA-DR7 was observed (relative risk, 26.2). Renal transplant recipients who have no apparent class switch from IgM to IgG production in response to Ag encoded by L1 of HPV 8 or possibly other EV-associated HPV are at an increased risk of skin cancer. The association with HLA-DR7 indicates a genetic control of skin cancer development or regression, involving genes in the class II region of the MHC.
人乳头瘤病毒（HPV），尤其是与疣状表皮发育不良（EV）相关的HPV 5、8、14、17、20和47，被认为在肾移植受者某些皮肤癌的发病机制中起作用。MHC I类和II类基因参与对病毒和肿瘤抗原的细胞免疫反应。对于有或没有皮肤癌的受者对HPV的体液反应了解甚少。我们调查了针对HPV 8早期（E）蛋白E7和主要衣壳晚期（L）蛋白L1的抗体的流行情况。此外，我们研究了HLA II类分子与这些抗体反应之间的关联。HPV 8的E7和L1开放阅读框被细菌表达为β-半乳糖苷酶融合蛋白，通过制备性凝胶电泳进行纯化。通过蛋白质印迹分析，对36例有皮肤癌的肾移植受者和91例无皮肤癌的受者的血清样本进行筛查，以检测针对HPV 8 E7和L1的IgG和IgM抗体。抗HPV 8 L1抗体的检测代表了对HPV 8以及可能其他与EV相关的HPV的免疫反应，因为该HPV亚属的代表之间可能会发生交叉反应。将针对HLA抗原的抗体反应用作对照。对HPV 8的L1有IgM抗体但无IgG抗体的受者（没有明显从IgM向IgG类别转换的患者），50%的病例患有皮肤癌，而产生IgG抗体的受者（对HPV 8的L1有明显良好体液反应的患者）只有18%的病例患有皮肤癌。与有良好体液反应的受者相比，没有类别转换的受者患皮肤癌的估计相对风险为4.5（95%置信区间，1.1至18.1）。我们发现针对HLA抗原的抗体反应与皮肤癌的发生之间没有关联。观察到针对HPV 8的L1或可能其他与EV相关的HPV编码抗原的抗体产生没有类别转换与HLA-DR7之间有很强的联系（相对风险，26.2）。对HPV 8的L1或可能其他与EV相关的HPV编码抗原没有明显从IgM向IgG产生类别转换的肾移植受者患皮肤癌的风险增加。与HLA-DR7的关联表明皮肤癌发生或消退存在遗传控制，涉及MHC II类区域的基因。
