Oral Immunoglobulin Levels are Not a Good Surrogate for Cervical Immunoglobulin Levels.

BACKGROUND: We sought to determine whether oral secretions could be used as a surrogate for cervical secretions for monitoring cervical immunoglobulin (Ig) levels. To do so, we examined (1) whether oral IgG and IgA levels correlated with those observed at the cervix, and (2) whether time of menstrual cycle and other factors previously reported to influence cervical Ig levels were associated with oral IgG and IgA levels. METHODS: We obtained oral samples from a group of 85 Costa Rican woman 25-35 years of age measured at three time points during one menstrual cycle. Total IgG and IgA levels were measured by ELISA. Generalized estimating equations methods that account for repeated measures were used to evaluate the association between oral and cervical Ig levels and to evaluate the association between various covariates and oral IgA and IgG levels. RESULTS: We did not observe an association between oral and cervical IgG [linear regression coefficient (LRC) 0.01; 95% CI, -0.05 to 0.07] and IgA levels (LRC 0.02; 95% CI, -0.04 to 0.08). Oral IgG and IgA levels were not influenced by phase of menstrual cycle, in contrast to what has previously been observed for cervical Ig levels. CONCLUSION: Our data suggest that oral IgG and IgA measures are not a good surrogate for cervical IgG and IgA levels. Future studies should examine whether antigen-specific antibody responses induced by vaccination correlate across mucosal sites.

Increased plasma levels of adipokines and inflammatory markers in older women with persistent HPV infection.

We observed diminished lymphoproliferation to multiple stimuli in older women with persistent cervical human papillomavirus (HPV) infection. Adipokines are a class of inflammatory cytokines that are altered in some persistent infections. The objective was to compare the level of adipokines and inflammatory cytokines in heparinized plasma from women with persistent HPV cervical infection (Cases, N=50, oversampled for their weak lymphoproliferation responses) with women with no evidence of persistent HPV cervical infection (Controls, N=50, oversampled for their strong lymphoproliferation responses). Plasma samples were analyzed with multiplex assays for adipokines and inflammatory cytokines. Cases had significantly elevated plasma levels of resistin (p<0.0001) and sFas (p=0.0038) as compared to controls. Risk of persistent HPV infection increased significantly with increasing levels of resistin and 8Fas. This is the first study to demonstrate elevated levels of resistin and sFas in HPV persistently infected, older women with decreased immune function expanding the understanding of the systemic inflammation and immune alterations in individuals persistently infected with HPV. Further studies within a larger cohort are needed to define the generalities of these findings and any role adipokines have in persistent HPV infection.

Elevated systemic levels of inflammatory cytokines in older women with persistent cervical human papillomavirus infection.

BACKGROUND: Defects in lymphoproliferative responses to mitogens/antigens in women >45 years old with a persistent type-specific human papillomavirus (HPV) infection have been reported. METHODS: To determine whether these defects were associated with altered cytokine profiles, plasma and peripheral blood mononuclear cell (PBMC) culture supernatants from 50 cases (oversampled for their reduced lymphoproliferative ability) and 50 uninfected controls (oversampled for their robust lymphoproliferative ability) were examined for 24 cytokines using multiplexed bead-based immunoassays and ELISA. RESULTS: The following plasma cytokines were significantly increased in cases relative to controls (cases versus controls; median pg/mL): interleukin (IL)-6, 393.1 versus 14.5; IL-8, 1,128.5 versus 43.9; tumor necrosis factor-alpha (TNF-alpha), 164.1 versus 9.2; macrophage inflammatory protein-1alpha (MIP-1alpha), 1,368.9 versus 25.5; granulocyte macrophage colony-stimulating factor (GM-CSF), 13.8 versus 7.3; IL-1beta, 8.3 versus 1.6 (all P < 0.0001); and IL-1alpha, 218.2 versus 169.5 (P = 0.02). We focused our analysis on the cytokines IL-6, IL-8, TNF-alpha, and MIP-1alpha due to their high fold change (>10) and highly statistically significant difference between cases and controls. Length of persistence or type of infection (high risk and low risk) did not affect these differences. IL-6, TNF-alpha, and MIP-1alpha levels were also increased in unstimulated PBMC culture supernatants from cases compared with controls (P < 0.05), however, the cytokine levels from phytohemagglutinin-stimulated PBMC culture supernatants were significantly lower in the cases (P < 0.0001). CONCLUSIONS: Persistent HPV infection in older women with evidence of immune deficit is associated with an increase in systemic inflammatory cytokines. IMPACT: Future studies are needed to determine whether the inflammatory profile is age dependent and to examine the role that inflammatory cytokines play in HPV-induced progression from infection to cervical cancer.