Seppanen Mikko, Meri Seppo, Notkola Irma-Leena, Seppala Ilkka J T, Hiltunen-Back Eija, Sarvas Heikki, Lappalainen Maija, Valimaa Hannamari, Palikhe Anil, Valtonen Ville V, Lokki Marja-Liisa
Department of Medicine, Division of Infectious Diseases, Helsinki University Central Hospital, Hospital District of Helsinki and Uusimaa, Helsinki, Finland.
J Infect Dis. 2006 Sep 1;194(5):571-8. doi: 10.1086/506477. Epub 2006 Jul 24.
Immunogenetic factors predisposing to recurrent genital herpes remain poorly characterized.
In a prospective case-control study, 52 consecutive patients with frequently recurring outbreaks of genital herpes were compared with 80 herpes simplex virus (HSV)-seropositive (types 1 and 2) and 70 HSV-seronegative control subjects. Immunoglobulins (Igs), type-specific anti-HSV-2 IgG and IgG subclass antibodies against glycoprotein G, levels of C3 and C4, and classical pathway hemolytic complement activity were measured, and IgG1 and IgG3 allotyping; C4 immunophenotyping; C4* real-time polymerase chain reaction (PCR) genotyping; and HLA-A*, B*, and DR* typing were performed.
The G3m(g),G1m(a/a(x)) haplotype was more frequent in patients than in HSV-seronegative control subjects (P=.047). Compared with all control subjects, low levels of total IgG1 (odds ratio [OR], 4.9 [95% confidence interval {CI}, 2.0-12.5]; P=.001) and IgG3 (OR 3.6 [95% CI 1.7-7.8]; P=.001), but not of anti-HSV-2 antibodies, were associated with recurrences. Levels of complement were lowest in patients. The C4* null type was negatively associated with neuralgia (OR, 0.2 [95% CI, 0.06-0.81]; P=.022).
Low levels of antibody-dependent cellular cytotoxicity-mediating IgG1 and IgG3 antibodies, partly dependent of allotype, may predispose to recurrent genital herpes. Antibodies produced by T helper type 1 responses, potentially against an unknown epitope, appear to be relevant in recurrences. In patients, C4* deficiencies are associated with protection from herpetic neuralgias, possibly through reduced inflammation.
导致复发性生殖器疱疹的免疫遗传因素仍未得到充分表征。
在一项前瞻性病例对照研究中，将52例连续出现频繁复发生殖器疱疹的患者与80例单纯疱疹病毒（HSV）血清阳性（1型和2型）和70例HSV血清阴性对照受试者进行比较。测量免疫球蛋白（Igs）、针对糖蛋白G的型特异性抗HSV-2 IgG和IgG亚类抗体、C3和C4水平以及经典途径溶血补体活性，并进行IgG1和IgG3同种异型分型；C4免疫表型分析；C4实时聚合酶链反应（PCR）基因分型；以及HLA-A、B和DR分型。
G3m（g）、G1m（a/a（x））单倍型在患者中比在HSV血清阴性对照受试者中更常见（P = 0.047）。与所有对照受试者相比，总IgG1水平低（优势比[OR]，4.9 [95%置信区间{CI}，2.0 - 12.5]；P = 0.001）和IgG3水平低（OR 3.6 [95% CI 1.7 - 7.8]；P = 0.001），但抗HSV-2抗体水平与复发无关。患者的补体水平最低。C4*无效型与神经痛呈负相关（OR，0.2 [95% CI，0.06 - 0.81]；P = 0.022）。
低水平的介导抗体依赖性细胞毒性的IgG1和IgG3抗体，部分依赖于同种异型，可能易患复发性生殖器疱疹。由1型辅助性T细胞反应产生的抗体，可能针对未知表位，似乎与复发有关。在患者中，C4*缺陷与预防疱疹性神经痛有关，可能是通过减少炎症实现的。
