Soluble fibrinogen-like protein 2 in condyloma acuminatum lesions.

INTRODUCTION: An imbalance in type 1 (Th1) and type 2 (Th2) T helper cells is associated with the development and recurrence of condyloma acuminatum (CA); however, the mechanisms underlying this imbalance remain unknown. We investigated soluble fibrinogen-like protein 2 (sFGL2), which is an effector of regulatory T cells (Tregs), to determine its role in the Th1/Th2 imbalance of CA. METHODOLOGY: Lesion and blood samples were obtained from 30 CA patients, and these samples were compared with genital skin and blood samples from 20 control subjects. Serum sFGL2, mRNA, and protein levels were estimated using ELISA, quantitative real-time polymerase chain reaction, and western blot, respectively. Immunohistochemical analyses were also conducted. RESULTS: Compared to controls, CA patients had decreased serum sFGL2 levels. However, sFGL2 mRNA and protein levels in the lesions of CA patients were significantly increased. Interleukin (IL)-4 and Foxp3 mRNA levels were upregulated, and interferon (IFN)-γ levels were downregulated in CA patients compared to those in controls. Additionally, the sFGL2 mRNA level positively correlated with Foxp3 and IL-4 levels and negatively correlated with IFN-γ and IL-17 levels. CONCLUSION: sFGL2 contributes to the underlying Th1/Th2 imbalance in CA pathogenesis.

Possible role of interleukin 21 and interleukin 33 in patients with genital warts.

Genital warts (GWs) are most prevalent sexually transmitted infections, presenting especially among the sexually active young population of both sexes. Efficient cell-mediated immunity is needed for regression of GWs. To clarify the reactivity of cellular immunity among patients with GWs by means of measurements of their levels of serum interleukin (IL)-21 and IL-33, hence, to identify the possible role of IL-21 and IL-33 in GWs, this study aimed to evaluate serum levels of IL-21 and IL-33 among patients with GWs in comparison with the results of the controls. Levels of serum IL-21 and IL-33 were assayed utilizing commercially enzyme-linked immune-sorbent assay kits in 45 patients with GWs and 45 healthy control subjects. Levels of serum IL-21 and IL-33 were significantly decreased among patients with GWs in comparison with the controls (p < .0001). There was a highly significant positive correlation between IL-21 and IL-33 (r = .73, p < .0001). Low levels of serum IL-21 and IL-33 could have a contributive role in development, persistence, severity, and recurrence of GWs which rely basically on the defectiveness of cell-mediated immunity. This could receive new light on nonconventional strategies for the prospective medical therapies of GWs by means of regulation of IL-21 and IL-33.

Comparison of Plasma Zinc Levels Among HIV+ and HIV- Subjects Infected with Condyloma Acuminata

Background: Condyloma acuminata is a type of human papilloma virus (HPV) infection in the anogenital area and often associated with immunosuppressive conditions, such as human immunodeficiency virus (HIV). Low plasma zinc levels could cause alteration of cellular immunity, leading to reduction of interleukin-2 (IL-2) and interferon-γ (IFN-γ), cytokines required for inhibition of HPV replication. Moreover, low plasma zinc levels could cause disruption of apoptotic regulation, results in the unimpeded proliferation of epithelial cells infected with HPV. This study aimed to compare the mean plasma zinc levels in condyloma acuminata patients with HIV and without HIV infection. Methods: This study used a cross-sectional method, involving 27 condyloma acuminata patients without HIV infection and 18 patients with HIV infection, who agreed to enroll and signed the informed consent. This study was conducted in the dermatology and venereology outpatient clinic in Sanglah Hospital and Kerti Praja Foundation, Denpasar. Bivariate analysis of the characteristics, age, sex orientation, location of lesion, clinical form of lesion, type of cases, duration of condyloma acuminata, age of the first sexual contact, comorbidity, treatment history, and mean plasma zinc level of condyloma acuminata patients with HIV and without HIV infection. The CD4+ cell count and history of ARV treatment were also obtained form patients with HIV infection. Results: A total of 45 subjects were diagnosed with condyloma acuminata, consisted of 27 subjects with condyloma acuminata without HIV infection and 18 subjects with HIV infection, showing average age of 32.04 ± 10.414. Mean plasma zinc levels in condyloma acuminata patients with HIV infection was significantly lower than subjects without HIV infection, and the difference in mean plasma zinc levels was 7.31 µg/dL (95% CI 2.25 - 12.37, p <0.05). Conclusions: The mean plasma zinc levels in condyloma acuminata patients with HIV was significantly lower than those of without HIV infection.

Seroprevalence of Cutaneous Human Papillomaviruses and the Risk of External Genital Lesions in Men: A Nested Case-Control Study.

BACKGROUND: A variety of cutaneous human papillomaviruses (HPV) are detectable in genital epithelial lesions in men and non-melanoma skin cancer patients. It remains unclear whether these viruses are associated causally with skin lesions. To date, no study has prospectively examined the association between cutaneous HPV seropositivity and development of external genital lesions (EGLs) in men. OBJECTIVES: To examine the association between seropositivity to cutaneous HPV types and the risk of subsequent development of EGLs. METHODS: A nested case-control study including 163 incident EGL cases and 352 EGL-free controls in the HPV Infection in Men (HIM) Study cohort was conducted. Cases were ascertained at each of up to 10 biannual clinical visits and verified through biopsy and pathological diagnoses. EGLs were categorized as condyloma, suggestive of condyloma, penile intraepithelial neoplasia (PeIN), and other EGLs. Archived serum specimens collected at baseline were tested for antibodies against 14 cutaneous HPV types (ß types (5, 8, 12, 14, 17, 22, 23, 24, 38, and 47), α type 27, γ type 4, µ type 1, and ν type 41) using a GST L1-based multiplex serology assay. Socio-demographic and sexual behavior data were collected through a questionnaire. Using logistic regression, adjusted odds ratios (AOR) and 95% confidence intervals (CI) were estimated. RESULTS: Overall, seropositivity to ≥1 cutaneous HPV type (any-HPV) and ≥1 ß types (any-ß) was 58.3% and 37.5% among other EGL cases, 71.6% and 46.8% among condyloma, 66.8% and 50.0% among PeIN, and 71.9% and 38.4% among controls, respectively. Type-specific seropositivity was most common for ɤ-HPV 4, µ-HPV 1, and ß-HPV 8. No statistically significant association was observed between any-HPV, any-ß, and type-specific HPV seropositivity and subsequent development of EGLs across all pathological diagnoses. CONCLUSIONS: Overall, seropositivity to cutaneous HPV was common among men; however, it appears that cutaneous HPV is not associated with the development of genital lesions in men.

Determining oxidant and antioxidant status in patients with genital warts.

OBJECTIVES: Warts are abnormal skin growths caused by human papilloma virus (HPV) infections within the skin of patients. Genital warts usually appear in the perianal and perigenital regions. Asymptomatic warts may be activated after years and may damage natural immunity. The inflammation that occurs during this process may lead to an imbalance between the prooxidant and the antioxidant systems. The aim of this study was to investigate erythrocyte glutathione peroxidase (GSH-Px) activity, serum paraoxonase enzyme levels, and oxidative stress levels in patients with genital warts. PATIENTS AND METHODS: In total, 32 patients with genital warts and 35 healthy subjects were included in this study. Erythrocyte GSH-Px activity, serum catalase activity, and paraoxonase enzyme, and malondialdehyde (MDA) levels were determined. RESULTS: Erythrocyte GSH-Px activity, serum MDA levels, and catalase activity were significantly higher in patients with genital warts than in controls (P < 0.01, P < 0.05, and P < 0.05, respectively). However, serum paraoxonase enzyme levels were not significantly different between groups (P > 0.05). Serum triglyceride levels were significantly lower in patients with genital warts than in controls (P < 0.01). However, there were no statistically significant differences between groups with respect to total cholesterol, high-density lipoprotein cholesterol, or low-density lipoprotein cholesterol levels (all P > 0.05). CONCLUSIONS: Our data suggest that oxidative stress is increased in genital warts. Increased oxidative stress levels may contribute to the pathogenesis of genital warts, and prolonged HPV infection due to chronic inflammation could also affect oxidative stress.

Pharmacokinetics of daily self-application of imiquimod 3.75% cream in adult patients with external anogenital warts.

Imiquimod 3.75% cream is a new formulation intended for daily self-application. The objective of this study was to characterize serum imiquimod pharmacokinetics under maximal use conditions. Adults with ≥8 warts or total wart area ≥100 mm² applied up to 1 packet of imiquimod 3.75% cream (250 mg cream, 9.375 mg imiquimod) once daily for 3 weeks. Blood was obtained prior to doses 1, 7, 14, and 21 and at selected time points after doses 1 and 21. Eighteen patients (13 men and 5 women) with a median wart count of 16 and total wart area of 60 mm² were enrolled. Day 21 mean (SD) serum C(max) was 0.49 (0.37) ng/mL, AUC0₋24 6.80 (3.59) ng·h/mL, and t(1/2) 24.1 (12.4) hours. Steady state was achieved by day 7 with ~2-fold increase in C(max) and AUC after multiple dosing. Overall, C(max) was higher and t(max) shorter in women, with comparable AUC0₋24. Imiquimod metabolites were sporadically quantifiable. No patients discontinued for adverse events; 1 interrupted dosing for an application site ulcer. Treatment-related adverse events occurred in 16.7% of the patients. In conclusion, serum imiquimod concentrations were low after daily self-application to external anogenital warts of up to 1 packet of imiquimod 3.75% cream for 21 days.

[Studies on the establishment of a method to detect HPV 6b E7-specific antibodies of serum and cervical secretion from patients with condyloma acuminatum and its epidemiological significance].

OBJECTIVE: To establish a method for detection of the human papi11omavirus (HPV) 6b E7-specific antibodies in serum and cervical secretion from patients with condyloma acuminatum (CA). METHODS: A full-length HPV 6b E7 gene was amplified by PCR from the CA tissue to construct the recombinant plasmid pET32a(+)/HPV 6b E7. The expression of prokaryotic protein was analyzed by SDS-PAGE and Western blot, then purified with Ni-NTA Agarose affinity column and used as an diagnostic antigen for establishing indirect ELISA method, to detect specific serum IgG and specific cervical secretion sIgA from 56 CA patients, 81 healthy control. Sera from 43 cervical cancer was served as control. HPV 6b DNA from 56 CA patients was identified by PCR. RESULTS: Data showed that the nucleotide homology of cloned sequence was 99.5%, compared to the standard sequences of HPV 6b E7 gene (GenBank accession number: NC001355). A high level expression of E7 fusion protein was obtained in prokaryotic expression system (40 µg/ml). Based on HPV 6b E7 fusion protein being used as coating antigen, results from ELISA showed that the absorbance rates (A) of serum IgG from CA, cervix cancer and healthy control groups were 1.82 ± 0.48, 1.36 ± 0.39 and 1.39 ± 0.27, respectively. The level of IgG antibody in the serum of CA group was significantly higher than that in cervix cancer group and healthy control (P < 0.05). The A values of cervical secretion sIgA in CA and healthy control groups were 0.63 ± 0.26 and 0.53 ± 0.06, respectively, while the level of sIgA antibody in the cervical secretion of CA group was also significantly higher than that in healthy controls (P < 0.05). The positive rate of HPV 6b E7 DNA in CA tissue was 78.6% (44/56) by PCR method. When compared the results measured by PCR, the HPV 6b E7-specific IgG and sIgA antibodies by ELISA used to detect the patients infected with HPV 6b infection, showed that the sensitivity rates were 68.2% (30/44) and 54.6% (24/44) respectively, and the specificity were all 100% (12/12). CONCLUSION: Based on the serum and cervical secretion specific HPV 6b E7 antibodies from patients with CA to diagnose HPV 6b infection, results showed medium sensitivity and high specificity, and could further be used to investigate the epidemiological characteristics of HPV 6b infection.

[Detection of peripheral blood Th1/Th2 and Tc1/Tc2 subsets in patients with condyloma acuminatum and its significance].

OBJECTIVE: To investigate the role of T-helper (Th) and cytotoxic T (Tc) lymphocyte polarization in the pathogenesis of condyloma acuminatum (CA) and its correlation with recurrence. METHODS: Three-colour immunofluorescent flow cytometry was used to detect the proportion of CD3+ CD8- /IFN-gamma+ (Th1), CD3+ CD8- /IL-4+ (Th2), CD3+ CD8+/IFN-gamma+ (Tc1) and CD3+ CD8+ /IL-4+ (Tc2) cells in the peripheral blood of CA patients and health controls. RESULTS: Compared to health controls, CA patients showed a decreased number of Th1 (P < 0.01) and Tc1 cells (P < 0.05), as well as a decreased Th1/Th2 and Tc1/Tc2 ratio (P < 0.05). Furthermore, in 15 recurrent CA patients the ratio of Th1/Th2 was remarkably decreased (P < 0.01), while the ratio of Tc1/Tc2 had no significant change in comparison with health controls. CONCLUSION: The decrease of Th1 and Tc1 subsets results in relative Th2 and Tc2 predominance, and this tendency is more significant in recurrent CA patients. The Th1 to Th2 and Tc1 to Tc2 shifts in CA patients could be responsible for the fact that human papilloma virus (HPV) is hard to be eliminated.

Expression of CD40 and CD40L on peripheral blood mononuclear cells in patients with condyloma acuminatum.

To observe the expression of CD40/CD40L on peripheral blood mononuclear cells (PBMC) in patients with condyloma acuminatum (CA), flow cytometry was employed to examine the expression of CD40 and CD40L on PMBC in 36 patients with CA and 20 healthy controls. Our results showed that mean level of CD40 expression in CA patients was significantly lower than that in the controls (6.58% +/- 2.74% vs 14.81% +/- 6.12%, t = 5.703, P < 0.05); the average level of CD40L in CA patients was also significantly lower than that in the controls (0.73% +/- 0.54% vs 2.67% +/- 2.43%, t = 3.532, P < 0.05). Our results suggest that the reduced costimulatory interaction of CD40 and CD40L in CA patients may be one of the important factors responsible for the low cellular immunity.

Correlation between the expression of Fas, Bcl-2 in peripheral blood lymphocytes and the level of IFN-gamma, IL-4 in serum of patients with condyloma acuminata.

In order to investigate the correlation between the expression of the apoptotic regulatory proteins (Fas, Bcl-2) in peripheral blood lymphocytes (PBLC) and the level of IFN-gamma and IL-4 in serum of the patients with condyloma acuminata (CA) in the immune pathogenesis of CA, indirect immunofluorescence labeling method of flow cytometer and solid sandwich ELISA method were performed for detecting the expression of Fas, Bcl-2 in PBLC and the level of IFN-gamma and IL-4 in serum of 60 cases of CA. The results showed the expression level of Fas in PBLC of CA was significantly higher than in the normal control group, but the expression level of Bcl-2 was significantly lower (both P<0.01). The level of IFN-gamma in serum of CA was significantly lower than in the normal control group (P<0.01), but IL-4 was significantly lower (both P<0.01). The expression of Fas in PBLC had a negative correlation with the level of IFN-gamma in serum of patients with CA, but had a positive correlation with the level of IL-4; The expression of Bcl-2 had a positive correlation with the level of IFN-gamma, but had a negative correlation with the level of IL-4. All the correlation coefficients had significant difference by t test (P<0.01). It was suggested abnormal apoptosis in PBLC, the suppressed secretion of the TH1-associated cytokines (eg: IFN-gamma) and the increased secretion of the TH2-associated cytokines (eg: IL-4) existed in the patients with CA and might play an important role in the immune pathogenesis of CA.

[Effects of BCG-PSN on serum levels of IL-4 and IL-12 in patients with condyloma acuminatum].

OBJECTIVE: To determine the effects of polysaccharide nucleic acid fraction of bacillus calmette guerin (BCG-PSN) on serum levels of interleukin-4 (IL-4) and interleukin-12 (IL-12) in patients with condyloma acuminatum (CA) and to investigate the mechamism of immunoregulation of BCG-PSN on CA. METHODS: Sixty CA cases were randomly divided into 2 groups. The serum levels of IL-4 and IL-12 were respectively measured by Double-antibody sandwich ELISA method before and after the treatment. The serum levels of IL-12 and IL-4 of health control were also measured. The recurrent rate of each group was used as an index to assess the effect of BCG-PSN in CA patients. RESULTS: Compared with healthy controls, the serum levels of IL-12 in patients with CA were decreased significantly (P < 0.05), while the serum levels of IL-4 were increased significantly (P < 0.05) before the treatment. The serum levels of IL-12 were negatively correlated with the serum levels of IL-4 (r = -0.287, P < 0.05). After the treatment, the serum levels of IL-12 were increased significantly( P < 0.05), and the serum levels of IL4 were decreased significantly (P < 0.05) in the treatment group. But in the control group, the serum levels of IL-12 and IL-4 were similar before and after the treatment (P > 0.05). The recurrent rate of treatment group was significantly lower than that of the control group (chi2 = 4.356, P < 0.05). CONCLUSIONS: There is an imbalance of Th1/Th2 cytokines production in patients with condyloma acuminatum. BCG-PSN could increase the serum level of IL-12 and decrease the serum level of IL-4 in CA patients. BCG-PSN could decrease the recurrent rate of CA. The effect may be related to the regulation and modulation of BCG-PSN to Thl/Th2 cytokines imbalance,which then enhances the cellular immunity in CA patients.

The expression of Fas/FasL in peripheral blood lymphocytes and the level of IL-2 in serum of patients with condyloma acuminata.

In order to investigate the role of the expression of the Fas/FasL in peripheral blood lymphocytes (PBLC) and the level of IL-2 in serum of patients with condyloma acuminata (CA) in the immune pathogenesis of CA, flow cytometry, indirect immunofluorescence labeling and ELISA were performed to detect the expression of the apoptotic regulatory proteins Fas/FasL in PBLC and the level of IL-2 in serum of 60 patients with different course of CA. The results showed that the expression of Fas/FasL in PBLC of the group of short course in CA was significantly higher than that of the normal controls (P < 0.05); the expression of Fas, FasL in PBLC of the group of long course CA was significantly higher than that of the group of short course and the normal controls (P < 0.05 and P < 0.01, respectively); the level of IL-2 in serum of the group of short and long course CA was significantly lower than that of the group of normal controls (P < 0.01); the negative relation was revealed between the expression of Fas/FasL in PBLC and the level of IL-2 in serum of patients with CA (r = -0.76, P < 0.01). It was suggested that the abnormal apoptosis in PBLC and decreased level of IL-2 in serum of CA might play an important role in the course of CA.

HIV infection: oral lesions, CD4+ cell count and viral load in an Italian study population.

The aims of this study were to assess types and prevalence of HIV-related oral lesions and to correlate these lesions to the main laboratory parameters such as CD4+ cell count and plasma HIV-RNA. The study population consisted of 104 consecutive HIV+ patients living in Sicily (M=67, 64.4%; F=37, 35.6%; median age=35 years). CD4+ cell count and viral load were measured within 24 h of oral examination. Data were managed and analysed by Epi-Info 6.0. HIV-related oral lesions, as classified by the EC-Clearinghouse, were diagnosed in 35.6% of patients: these were of the Strongly Associated (SA) type in 22.1%, the Less Common Associated (LCA) type in 12.5%, and the Lesions Seen in HIV Infection (LS) type in 3.8%. CD4+ cell counts <200 x 10(6)/l were significantly associated only with SA lesions (P=0.03); median values of CD4+ cell count were also significantly correlated (P=0.02). Viral load, expressed both by median values of copies/ml (P=0.0001) and log10 copies/ml (P=0.0003), was significantly associated only with SA lesions. Treatment failure was significantly correlated to SA lesions (P=0.04). Besides the confirmed correlation with CD4 depletion, the strong association with a high level of viral load could make SA oral lesions a useful tool for identifying progression of HIV infection and could be of value in monitoring antiretroviral therapy.

Phase I safety and antigenicity of TA-GW: a recombinant HPV6 L2E7 vaccine for the treatment of genital warts.

A phase I double-blind, randomized, placebo-controlled study was carried out in healthy subjects to assess the safety and immunogenicity of TA-GW, a recombinant HPV6 L2E7 fusion protein vaccine for the treatment of genital warts. Forty-two healthy male volunteers were randomised to receive three intramuscular injections of either 0, 3, 30 or 300 microg of recombinant L2E7 adsorbed onto Alhydrogel. Two vaccination schedules were compared: weeks 0, 1 and 4 (accelerated schedule) and weeks 0, 4 and 8 (classical schedule). Subjects were monitored for adverse events throughout. Immunogenicity was assessed by measuring L2E7 specific in vitro T cell proliferative responses, production of IFNgamma and IL-5 and serum antibodies. Dose-dependent and long-lived T and B cell immune responses were elicited by TA-GW with both vaccination schedules. In conclusion, TA-GW is both safe, well-tolerated and immunogenic. The results allow the selection of the 300-microg vaccine formulation and accelerated vaccination schedule for phase II trials in patients with genital warts.

The cellular immune system in female patients with or without genital warts: a study of peripheral white blood cell components.

The immune system plays a vital role in the fight against infections. The commonest viral infections treated in the genitourinary medicine (GUM) departments are genital warts. Knowledge about the status of the immune system in these patients may help in their clinical management. This study compares the values of various blood cell components in the peripheral blood of 2 groups of female patients--those with genital warts against those without genital warts. The mean monocyte count was lower among patients with genital warts.

Serum levels of soluble tumor-necrosis-factor receptors in patients with benign and malignant HPV-associated anogenital lesions.

The levels of type-I and type-II soluble TNF-alpha receptors (sTNF-Rs) were evaluated in sera from patients with various human-papillomavirus-(HPV)-associated benign and malignant anogenital lesions using specific enzyme-linked immunobiological assays. In patients with benign HPV6/11-associated condylomata acuminata, the levels of sTNF-RI were significantly increased, while sTNF-RII were in normal range. Both types of sTNF-Rs were in normal range in patients with benign HPV16-associated grade-I/II and grade-III cervical intra-epithelial neoplasia. However, their levels were significantly increased in patients with HPV16/18-associated squamous cervical cancer and anogenital Bowen's carcinoma. Sera from patients with condylomata acuminata and anogenital carcinomas displayed significantly increased TNF-alpha-inhibitory activity, as revealed by L929 cell-cytotoxicity assay. Increased serum TNF-alpha-inhibitory activity correlated with higher levels of sTNF-Rs. Furthermore, this inhibitory activity could be specifically abrogated by htr9 and utr1 monoclonal antibodies recognizing TNF-RI and TNF-RII respectively. Our results strongly suggest that serum sTNF-Rs may protect tumor cells from cytotoxic/cytostatic effects of locally released TNF-alpha, and that elevated levels of circulating sTNF-Rs may facilitate the growth of HPV-associated anogenital lesions.

Isolation and characterization of human papillomavirus type 6-specific T cells infiltrating genital warts.

The potential role of T cells in the control of human papillomavirus type 6 (HPV-6) infections is an appealing premise, but their actual role has been sparsely investigated. Since HPV-6 infections are confined to the epithelium, such an investigation should focus on the T cells present at the site of infection (i.e., the warts). Therefore, we isolated wart-infiltrating lymphocytes (WIL) from patients with clinically diagnosed anogenital warts. These WIL were characterized by their phenotype and their specificity for E7 and L1 proteins of HPV-6. The phenotype of WIL varied drastically from patient to patient, as determined by their expression of CD4, CD8, T-cell receptor alpha/beta chain (TCR alpha beta), and TCR gamma delta. Despite this heterogeneity in phenotype, HPV-6 E7 and/or L1-specific WIL, as determined by lymphoproliferation, could be isolated from more than 75% of the patients studied. Among all L1 peptides recognized by WIL, peptides 311-330 and 411-430 were the most consistently detected, with seven of nine patients for whom L1 peptide reactivity was observed responding to at least one of them. Moreover, the HPV-6 epitopic peptides recognized by WIL differed to some extent from those recognized by peripheral T cells.

Detection of serologic neutralizing antibodies against HPV-11 in patients with condyloma acuminata and cervical dysplasia using an in vitro assay.

This study was designed to investigate if neutralizing antibodies against HPV-11 are detectable in the serum of patients with condyloma acuminata (CA) or cervical intraepithelial neoplasia (CIN) using an in vitro infectivity assay for HPV-11. Purified HPV-11 virions were extracted from xenografted condyloma tissues implanted into athymic mice and used to infect cultured neonatal human foreskin keratinocytes (HFK) and an immortalized adult skin cell line (HaCaT). The presence of HPV-11-specific E1--E4 mRNA as detected by reverse transcriptase-polymerase chain reaction was indicative of early infection. Sera previously characterized for reactivity to HPV-11 and HPV-11 VLP (virus-like particles) by ELISA were tested for the ability to prevent HPV-11 in vitro infectivity. Neutralizing antibodies against HPV-11 were demonstrated when monoclonal antibodies or patient serum preincubated with HPV-11 virions prevented the infection of either of the two cell cultures, as shown by the absence of the E1--E4 mRNA transcript. Eleven (of 20) patients with CA were strongly ELISA reactive against HPV-11 virus-like particles. Five of these 11 patients also had detectable levels of neutralizing antibodies in their serum. It was also demonstrated that the neutralizing properties of the serum were titratable by endpoint dilution. None of 15 patients with CIN had detectable neutralizing antibodies against HPV-11. Neutralizing antibodies against HPV-11 can be detected in some patients with CA and the neutralizing effects of the patient sera can be titrated by endpoint dilution. The in vitro assay for the detection of neutralizing antibodies against HPV-11 may have utility for investigating the natural history of HPV infection and resolution, as well as assessing the efficacy of any putative HPV vaccine.

Antibodies to human papillomavirus type 11 virus-like particles in sera of patients with genital warts and in control groups.

We analysed by ELISA a total of 478 human sera for the presence of antibodies to HPV-11 virus-like particles. The sera were obtained from patients with current genital warts (group CO), from males attending the hospital for fertility disorders (group MA), from blood donors (group BD) and from patients hospitalized for reasons unrelated to HPV infections (group HO). Antibody prevalence was higher in male patients of group CO (23.0%) as compared to males of groups MA (3.2%; P < 0.0001), HO (5.3%; P = 0.01) and BD (16.7%; NS). In addition, there was a significant difference in antibody titre between the males of group CO compared to group MA. Within the whole sample the absorbance of sera from females was higher than in specimens from males (P < 0.0001). A small subset of the sera was also tested by radioimmunoprecipitation assay (RIPA). There was good agreement between the data obtained by ELISA and RIPA.