Cervical Secretions in Pregnant Women Colonized Rectally with Group B Streptococci have High Levels of Antibodies to Serotype III Polysaccharide Capsular Antigen and Protein R

Group B streptococci (GBS) colonizing the female genital tract will often infect newborn infants during delivery. In 200 pregnant women studied, 14% were colonized with GBS in the cervix, 12% in the rectum, and 9% in both cervix and rectum. We have previously reported that antibody levels to GBS serotypes Ia, II, and III in sera and cervical secretions were increased in women colonized in the rectum and/or cervix, when analyzed by a whole-cell ELISA. Here, we report the levels of antibodies to GBS serotype III capsular polysaccharide antigen (CPS III) and to protein antigen R₄, which are present in most GBS III strains. Compared to culture-negative women, the group of women colonized rectally had markedly elevated levels of immunoglobulin (Ig)A and IgG antibodies in cervical secretions to both CPS III and protein R₄ ( P  < 0.01 and P  < 0.001, respectively). In sera, the corresponding differences between culture-negative and culture-positive women were less pronounced, or not present. In contrast to antibody levels to whole-cell GBS, antibody levels to CPS III and protein R₄ in cervical secretions were not significantly increased in women colonized only in the cervix, except that IgA antibodies to protein R₄ were slightly elevated ( P  < 0.05). These findings suggest that capsular type-specific polysaccharides and protein R₄ in a mucosal vaccine might induce protective antibodies against GBS colonization of the uterine cervix.     

Comparison of the oral, rectal, and vaginal immunization routes for induction of antibodies in rectal and genital tract secretions of women.

To determine which mucosal immunization routes may be optimal for induction of antibodies in the rectum and female genital tract, groups of women were immunized a total of three times either orally, rectally, or vaginally with a cholera vaccine containing killed Vibrio cholerae cells and the recombinant cholera toxin B (CTB) subunit. Systemic and mucosal antibody responses were assessed at 2-week intervals by quantitation of CTB-specific antibodies in serum and in secretions collected directly from mucosal surfaces of the oral cavity, rectum, cervix, and vagina with absorbent wicks. The three immunization routes increased levels of specific immunoglobulin G (IgG) in serum and specific IgA in saliva to similar extents. Rectal immunization was superior to other routes for inducing high levels of specific IgA and IgG in rectal secretions but was least effective for generating antibodies in female genital tract secretions. Only vaginal immunization significantly increased both specific IgA and specific IgG in both the cervix and the vagina. In addition, local production of CTB-specific IgG in the genital tract could be demonstrated only in vaginally immunized women. Vaginal immunization did not generate antibodies in the rectum, however. Thus, generation of optimal immune responses to sexually transmitted organisms in both the rectal and the genital mucosae of women may require local immunization at both of these sites.     

Self-sampled and air-dried cervicovaginal secretions can be used for analyses of mucosal antibodies

Cervicovaginal secretions were collected from 26 women (13 premenopausal and 13 postmenopausal) using a new sampling device (MucoSafe™) with an absorbent which was introduced into the vagina and retrieved by the women themselves, after which it was air-dried and stored for months at room temperature until extraction of immunoglobulins. Cervical secretions were also collected by absorbent cylindrical wicks (Polyfiltronics) which were introduced into the cervical canal during speculum examination and thereafter kept frozen until extraction. The concentrations of specific IgA and IgG antibodies (to group B streptococci) in extracts from both methods were corrected by reference to total immunoglobulin levels. Three pairs of samples, all from postmenopausal women, were excluded from analysis due to undetectable levels of antibodies in the MucoSafe™ specimen. In the remaining 23 pairs, corrected concentrations of IgA and IgG antibodies in samples obtained by MucoSafe™ correlated well with the corresponding concentrations in wick samples, R=0.84 (p<0.0001) and R=0.69 (p=0.0002), respectively. Thus, cervicovaginal secretions for antibody measurements can be obtained by this novel method for self-sampling, obviating the need for speculum examination and storage of frozen samples.     

Systemic and mucosal immune responses in mice after mucosal immunization with group B streptococcus type III capsular polysaccharide-cholera toxin B subunit conjugate vaccine

Group B streptococci (GBS) colonize the female genital and rectal tracts and can cause invasive infection in susceptible newborns. An optimally effective GBS vaccine should induce mucosal and systemic immunity. In this study, we investigate the local and systemic immune responses to GBS type III capsular polysaccharide (CPS) after mucosal vaccination of mice via intranasal, peroral, rectal, and vaginal routes, with GBS type III CPS conjugated with recombinant cholera toxin B subunit (GBS III CPS-rCTB). Cholera toxin (CT) was added as an adjuvant. Immunoglobulin G (IgG) and IgA antibodies to the CPS were tested in serum, lungs, and intestinal, rectal, and vaginal extracts by enzyme-linked immunosorbent assay. The conjugated CPS administered by intranasal, peroral, rectal, and vaginal routes was much more effective at inducing both mucosal and systemic antibody responses to GBS III CPS than was unconjugated CPS. The CPS-specific immune responses in various organs were dependent on the route of immunization. Generally, the highest levels of IgA and IgG were generated in the regions or sites of the conjugate exposure. Thus, intranasal vaccination elicited the highest anti-CPS IgA and IgG antibody levels in the lungs, whereas peroral administration in the intestinal site and vaginal vaccination elicited the highest antibody levels in the vagina. Rectal vaccination was superior to the other routes in inducing high antibody levels in the rectum. The four routes of mucosal vaccination also induced distant antibody responses to CPS. Rectal vaccination induced high specific IgA levels in the vagina and intestine, and oral administration induced high specific IgA levels in the lungs and rectum. All four routes of vaccination with the conjugate elicited similarly high levels of anti-CPS IgG in serum. Intranasal vaccination with different doses of the conjugate (10, 30, and 80 microg of CPS) did not have a significant influence on the anti-CPS specific antibody responses. Intranasal immunization induced better antibody responses when one dose of the conjugate was divided and given on three consecutive days compared to administration of the full dose on one occasion. In conclusion, rectal and vaginal vaccination may be the best way of stimulating anti-CPS immune responses in the rectal and vaginal tracts, while high levels of anti-CPS antibodies in the lungs can be achieved after intranasal administration. The vaccination regimen thus might influence the mucosal immune response to CPS. This conjugate may serve as an effective mucosal vaccine for preventing mucosal colonization and invasive infection caused by GBS.     

Seroprevalence of antibodies to group B streptococcal polysaccharides in Gambian mothers and their newborns.

In developing countries, little is known about the relationship between group B streptococcal (GBS) colonization in pregnant women and serum antibody levels to capsular polysaccharide antigens of these organisms. This study examined the prevalence of antibodies to two polysaccharides of GBS, Ia and III, in 124 Gambian women with known GBS colonization at delivery and their newborns. Mean antibody levels in maternal-cord serum pairs were 4.06 +/- 0.25 micrograms/mL and 2.64 +/- 0.20 micrograms/mL for type Ia GBS, and 1.1 +/- 0.52 microgram/mL and 0.78 +/- 0.43 microgram/mL for type III GBS. Women colonized with type V GBS had significantly higher antibody levels to type III GBS than did noncolonized women, but no difference was found when these groups were compared for antibody levels to type Ia GBS. Women > or = 20 years had significantly higher antibody levels to type III GBS compared with younger women and those colonized by other GBS serotypes. Maternal antibodies to types la and III GBS were transferred across the placenta to newborns. The rarity of GBS disease in Gambia and other developing countries may be due to the prevalence of maternally derived GBS antibodies, the low prevalence of colonization with serotype III strains, or other undefined factors.     

Effect of uterine immunization and oestradiol on specific IgA and IgG antibodies in uterine, vaginal and salivary secretions.

Levels of IgA and IgG antibodies were measured in uterine and vaginal secretions to examine the effect of uterine immunization on the genital tract humoral immune system. When ovariectomized animals were immunized on Day 0 and boosted 13 days later by placing sheep erythrocytes (SRBC) directly in the uterine lumen (UT/UT) immunization), a pronounced IgA and IgG antibody response was detected in uterine secretions measured on Day 26. This response was 20-30-fold greater than that measured following Peyer's patch immunization and boosting (PP/PP) and Peyer's patch immunization followed by uterine boosting (PP/UT). In contrast to uterine antibody responses that were oestradiol-dependent following PP/PP and PP/UT immunization, UT/UT immunization resulted in IgA and IgG antibody responses that were hormonally independent. To determine whether immunological information is distributed beyond the immediate site of immunization, ovariectomized rats were immunized and boosted by injection of SRBC into one uterine horn. When uterine secretions from the contralateral (non-immune) horns were analysed, IgA and IgG antibodies were found in uterine secretions after oestradiol stimulation. IgA and IgG antibodies were also present in vaginal secretions following UT/UT immunization and ligation of uteri at the utero-cervical junction. This response was hormonally dependent in that vaginal antibody levels were lowered by oestradiol treatment. IgG but not IgA antibodies were also found in saliva of UT/UT immunized animals. Oestradiol had no effect on salivary IgG levels in contrast to those of the genital tract. In summary, these experiments indicate that immunization of uteri can elicit pronounced IgA and IgG antibody responses in uterine secretions and this response is not altered by oestradiol. Moreover, immunization at one site in the genital tract results in the appearance of antibodies at other uterine sites (the contralateral-non-immunized horn), in vaginal secretions, in serum and at other mucosal sites, such as the salivary glands.     

Induction of specific immunoglobulin A in the small intestine, colon-rectum, and vagina measured by a new method for collection of secretions from local mucosal surfaces.

In order study patterns of local antibody responses following mucosal immunization of mice via different routes, a method for collection of secretions directly from mucosal surfaces was developed. Mice were immunized on days 0, 10, 17, and 24 by administration of cholera toxin into the oral cavity, stomach, colon-rectum, or vagina. At sacrifice on day 32, absorbent wicks were placed in the oral cavity and, via an applicator tube, into the vagina and distal colon-rectum and along the entire small intestine after flushing of luminal contents. Protein was quantitatively extracted from wicks, and specific anti-cholera toxin immunoglobulin A (IgA) and IgG were measured by enzyme-linked immunosorbent assay. Concentrations of specific IgA in secretions at various mucosal sites were dramatically influenced by the route of immunization. Oral immunization effectively induced IgA in saliva, and the intragastric route was optimal for induction of IgA in the small intestine. High levels of specific IgA appeared on the colonic-rectal mucosal surface only after rectal delivery of antigen. Oral, gastric, and rectal immunizations also produced distant responses in the vagina. Following vaginal immunization, however, neither local nor distant IgA responses were detected. These results suggest that vaccines intended for protection of colonic-rectal and vaginal mucosal surfaces might best be administered by the rectal route.     

Rectal Immunization for Induction of Specific Antibody in the Genital Tract of Women

The purpose of the current study was to examine potential routes of vaccine administration for the induction of antigen-specific responses in the genital tract of women. Sixteen women were enrolled in this study, and the level of influenza-specific antibodies induced in the genital tract was measured after rectal or intramuscular immunizations. Both methods of administration induced significant increases in the concentration of flu-specific IgA found in cervical secretions within 28 days after vaccination. Initially flu-specific IgG antibodies were not induced in the genital tract by either route. As expected both IgA and IgG flu-specific antibodies were dramatically increased in serum after intramuscular vaccination. In contrast, rectal administration did not induce significant IgA responses, and only small flu-specific IgG increases in serum. Six months after administration, IgA flu-specific antibody concentrations were significantly higher than baseline levels in vaginal secretions and saliva isolated from both subject groups and flu-specific IgG concentrations in cervical secretions were high in the rectal immunization group. The long-term presence of both IgG and IgA antibody in genital secretions suggests that rectal immunization may be an effective method for induction of immune protection in the genital tract of women.     

Bovine venereal vibriosis: variations in immunoglobulin class of antibodies in genital secretions and serum

The immunoglobulin classes of antibodies to Campylobacter (Vibrio) fetus in cervicovaginal mucus (CVM) were determined by the indirect fluorescent antibody test at sequential periods, since the order of class appearance has not been established for specific secretory immune responses. In the local immune response to C. fetus immunoglobulin M (IgM) antibodies appeared first, immunoglobulin A (IgA) antibodies next, and immunoglobulin G (IgG) last. IgM antibodies were quite transient, but IgG antibodies remained longer, and those of the IgA class persisted until the end of the experimental period (up to 10 months). Since differences appear to exist between immune mechanisms at cervicovaginal and uterine sites, as well as between immune responses induced by local and systemic immunizations, the immunoglobulin classes of antibodies in uterine secretions were compared with the classes in CVM and serum. Uterine antibodies arose coincidently with uterine lesions in heifers slaughtered after short periods of infection. In convalescent animals only IgA antibodies were found in CVM, whereas the predominant class of antibodies in the uterine secretions was IgG(1) in three of four animals studied. Only IgG antibodies were detected in CVM and uterine secretions of systemically immunized animals. These findings could account for faster clearance of C. fetus from the uterus than from the cervicovaginal area in locally infected animals and for failure of colonization in systemically immunized animals, because IgG antibodies are good opsonins and IgA antibodies are not. IgA antibodies do immobilize C. fetus, however, so they could prevent recolonization of the uterus in cervicovaginal carriers.     

Failure of serology in diagnosing chlamydial infections of the female genital tract.

Chlamydia trachomatis was recoved from 20% (36/180) of women attending a venereal disease clinic. All infected women had chlamydial antibodies in their serum and cervical secretions. However, the background rates of chlamydial antibody in chlamydia-negative women were very high. Measurement of antibodies in serum (complement fixation or immunoglobulin G [IgG] and IgM by microimmunofluorescence) or cervical secretion (IgG, IgM, IgA or secretory IgA classes) did not result in predictive values of greater than 32%. It is concluded that the detection of chlamydial antibodies in serum or cervical secretions cannot be substituted for agent isolation in diagnosing these infections.     

Kinetics of local and systemic immune responses after vaginal immunization with recombinant cholera toxin B subunit in humans

Vaginal vaccination seems to be the best strategy for inducing specific immunoglobulin A (IgA) and IgG antibody responses in the female genital tract. The relative efficiencies of one, two, and three vaginal doses of recombinant cholera toxin B subunit (CTB) in generating mucosal and systemic immune responses in healthy women were evaluated, and the kinetics of the immune responses were monitored for responding volunteers for up to 12 months after the last vaccination. A single dose of CTB failed to generate CTB-specific IgA antibody responses in cervical secretions. Two vaccinations induced significant increases in IgA antitoxin titers in seven of nine volunteers, and four volunteers also developed IgG antitoxin responses. The magnitudes of the responses were 20-fold for IgA antitoxin and 7.1-fold for IgG antitoxin. A third vaccination did not significantly increase the antitoxin responses, although the frequency of IgG responses was slightly higher than that after the second vaccination. In serum, CTB-specific antibodies were observed already after a single vaccination. However, two vaccinations were required to induce marked IgA as well as IgG antitoxin titer increases in the majority of volunteers. The postvaccination levels of antitoxin antibodies in serum were comparable after two and three vaccinations. At 12 months after vaccination, significantly elevated IgA and IgG antitoxin levels in cervical secretions could still be detected in approximately half of the volunteers who had initially responded to the vaccine. Antitoxin titer increases in serum were found in most of the vaccinees at follow-up.     

Kinetics of Local and Systemic Immune Responses after Vaginal Immunization with Recombinant Cholera Toxin B Subunit in Humans

Vaginal vaccination seems to be the best strategy for inducing specific immunoglobulin A (IgA) and IgG antibody responses in the female genital tract. The relative efficiencies of one, two, and three vaginal doses of recombinant cholera toxin B subunit (CTB) in generating mucosal and systemic immune responses in healthy women were evaluated, and the kinetics of the immune responses were monitored for responding volunteers for up to 12 months after the last vaccination. A single dose of CTB failed to generate CTB-specific IgA antibody responses in cervical secretions. Two vaccinations induced significant increases in IgA antitoxin titers in seven of nine volunteers, and four volunteers also developed IgG antitoxin responses. The magnitudes of the responses were 20-fold for IgA antitoxin and 7.1-fold for IgG antitoxin. A third vaccination did not significantly increase the antitoxin responses, although the frequency of IgG responses was slightly higher than that after the second vaccination. In serum, CTB-specific antibodies were observed already after a single vaccination. However, two vaccinations were required to induce marked IgA as well as IgG antitoxin titer increases in the majority of volunteers. The postvaccination levels of antitoxin antibodies in serum were comparable after two and three vaccinations. At 12 months after vaccination, significantly elevated IgA and IgG antitoxin levels in cervical secretions could still be detected in approximately half of the volunteers who had initially responded to the vaccine. Antitoxin titer increases in serum were found in most of the vaccinees at follow-up.     

Distribution of Monoclonal Antibodies in Intestinal and Urogenital Secretions of Mice Bearing Hybridoma 'Backpack' Tumours

Mice bearing IgA hybridoma 'backpack' tumours have been used to demonstrate that secretion of a single monoclonal IgA can protect against mucosal infection, but the relevance of this model to normal IgA protection is not clear. The authors analysed the distribution of specific monoclonal and total antibodies in bile, local intestinal secretions, cervical-vaginal secretions, urine and serum of mice bearing anti-cholera toxin (CT) IgA and IgG backpack tumours, with and without bile duct ligation. Backpack tumours resulted in high levels of both anti-CT and total IgA or IgG in serum, and IgA (but not IgG) in bile. Secretions recovered by absorbent filter 'wicks' from mucosal surfaces throughout the intestines of backpack tumour mice contained significant concentrations of monoclonal anti-CT IgA, but total IgA levels were as in normal mice. Neither monoclonal nor total IgA levels on mucosal surfaces were altered by bile duct ligation. Furthermore, anti-CT monoclonal IgA levels in local intestinal secretions of backpack tumour mice were comparable to specific polyclonal IgA levels previously elicited by mucosal immunization with CT. Thus, IgA-mediated protection against enteric challenge in the backpack tumour model may be a valid predictor of protection provided by natural mucosal immunization in vivo . High monoclonal IgA levels in bile, urine and the female genital tract, however, may not reflect the situation in normal immunized mice.     

Modified wick method using Weck-Cel sponges for collection of human rectal secretions and analysis of mucosal HIV antibody

Weck-Cel sponges were examined for suitability as an absorbent material for nontraumatic collection of rectal secretions in humans. Sponges were tested in vitro and determined by quantitative enzyme-linked immunosorbent assay (ELISA) to be capable of releasing 100% of absorbed albumin and all immunoglobulin subtypes after treatment with detergent-supplemented buffer. Protein composition in rectal secretions collected from normal women with dry sponges (DS) or with sponges previously softened by moistening with saline (MS) was subsequently compared. DS secretions showed evidence of contamination with blood and interstitial fluid-derived albumin, immunoglobulin G (IgG), and monomeric IgA. MS secretions appeared to represent local mucosal secretions more accurately because they contained negligible blood, a greater percentage of secretory IgA within the total IgA, and both lower albumin/IgG ratios and more dramatic alterations in IgG subclass distribution compared with corresponding serum. Anti-HIV IgG, IgM, IgA, and antibodies with secretory component could be demonstrated by ELISA in rectal secretions collected with moist sponges from 8 of 8, 1 of 8, 5 of 8, and 3 of 8 HIV-infected women, respectively. The data show that Weck-Cel sponges, if premoistened, can be used to collect rectal fluids nontraumatically and to obtain quantitative information about concentrations of immunoglobulins and specific antibodies on rectal mucosal surfaces.     

Nasal and Vaginal Vaccinations Have Differential Effects on Antibody Responses in Vaginal and Cervical Secretions in Humans

Sexually transmitted diseases are a major health problem worldwide, but there is still a lack of knowledge about how to induce an optimal immune response in the genital tract of humans. In this study we vaccinated 21 volunteers nasally or vaginally with the model mucosal antigen cholera toxin B subunit and determined the level of specific immunoglobulin A (IgA) and IgG antibodies in vaginal and cervical secretions as well as in serum. To assess the hormonal influence on the induction of antibody responses after vaginal vaccination, we administered the vaccine either independently of the stage in the menstrual cycle or on days 10 and 24 in the cycle in different groups of subjects. Vaginal and nasal vaccinations both resulted in significant IgA and IgG anti-cholera toxin B subunit responses in serum in the majority of the volunteers in the various vaccination groups. Only vaginal vaccination given on days 10 and 24 in the cycle induced strong specific antibody responses in the cervix with 58-fold IgA and 16-fold IgG increases. In contrast, modest responses were seen after nasal vaccination and in the other vaginally vaccinated group. Nasal vaccination was superior in inducing a specific IgA response in vaginal secretions, giving a 35-fold increase, while vaginal vaccination induced only a 5-fold IgA increase. We conclude that a combination of nasal and vaginal vaccination might be the best vaccination strategy for inducing protective antibody responses in both cervical and vaginal secretions, provided that the vaginal vaccination is given on optimal time points in the cycle.     

Influence of exogenous reproductive hormones on specific antibody production in genital secretions after vaginal vaccination with recombinant cholera toxin B subunit in humans

The objective of this study was to investigate the influence of exogenous reproductive hormones on the local and systemic production of specific immunoglobulin A (IgA) and IgG antibodies after vaginal vaccination with recombinant cholera toxin subunit B (CTB). Three groups of women using either progesterone-containing intrauterine devices (n=9), oral contraceptives (n=8), or no hormonal contraceptive methods (n=9) were vaginally immunized twice, 2 weeks apart. Cervical secretions, vaginal fluids, and serum were collected before and after vaccination. Total and CTB-specific IgA and IgG antibodies in genital secretions and serum were analyzed by enzyme-linked immunosorbent assay. A majority of the women presented strong CTB-specific IgA and IgG antibody responses in cervicovaginal secretions after vaccination, whereas the antitoxin responses in serum were weaker. Exogenously administered steroid hormones did not seem to have any impact on the production of specific antibodies. Both the frequencies and the magnitudes of IgA and IgG antitoxin responses in genital secretions were comparable among the three immunization groups. An association, in particular for IgA, was found between the magnitudes of the CTB-specific antibody responses in cervical secretions and vaginal fluids after vaccination. The sensitivities and positive predictive values of vaginal antibody analyses to reflect responses in cervical secretions were also high, suggesting that vaginal fluids alone might be used for evaluation of genital immune responses in large-scale vaccination studies in the future.     

Immune response of the female rat genital tract after oral and local immunization with keyhole limpet hemocyanin conjugated to the cholera toxin B subunit.

The immune response of the female rat genital tract was evaluated with Lewis rats given primary and secondary immunizations with keyhole limpet hemocyanin (KLH) alone or coupled to the cholera toxin (CT) B subunit (CTB) by the oral or intravaginal-uterine route or a combination of routes. CT (2 to 5 micrograms) was administered as an adjuvant with the KLH-CTB conjugate. While a significant mucosal immunoglobulin A (IgA) response was induced by KLH, there were no significant differences among the immunized groups in the levels of IgA antibodies in salivary gland, gut, vaginal, and uterine secretions, with the exception that rats immunized only orally with the KLH-CTB conjugate lacked a detectable vaginal response. Levels of IgA antibodies to CT, however, were significantly increased in genital tract secretions of rats immunized locally versus orally with the KLH-CTB conjugate. Antibody activity of the IgG isotype against both KLH and CT was significantly elevated in genital tract secretions of rats immunized with KLH-CTB by the oral or intravaginal-uterine route and given genital tract boosters, in comparison with the results for the other groups. IgM antibody titers were generally negligible in the different secretions. An enzyme-linked spot-forming assay revealed IgA and IgG antibody-secreting cells in salivary gland and uterine tissues. A highly significant correlation between the numbers of antibody-secreting cells and antibody titers existed for uterine IgG but not IgA responses to KLH among the different groups of rats. In conclusion, a vigorous local immune response was induced after immunization of the female rat reproductive tract alone or in combination with peroral challenge with the KLH-CTB conjugate.     

Persistence of chlamydial antibodies after pelvic inflammatory disease.

The persistence of chlamydial immunoglobulin G (IgG) antibodies and long-term sequelae of pelvic inflammatory disease (PID) were studied in 70 women who had been treated for PID 3 to 6 years previously. Fifty-one women had had PID associated with Chlamydia trachomatis infection (Chlamydia group), and 19 women had had PID not associated with C. trachomatis (non-Chlamydia group). Chlamydial IgG antibodies, as determined by the indirect immunofluorescence test with inclusions of C. trachomatis L2 as antigens, persisted at stable levels in 43% of the women for up to 6 years; 43% of the women showed a decrease in IgG titer, and 13% showed an increase. IgA antibody levels in serum correlated with IgG antibody levels in serum and with the presence of cervical IgA antibodies. Both serum antibodies and cervical IgA antibodies were more often found in the Chlamydia group. Forty-two percent of the women were infertile. Every fifth subsequent pregnancy was ectopic. The presence of cervical IgA antibodies might protect the women from tubal damage.     

Serological responses to papillomavirus group-specific antigens in women with neoplasia of the cervix uteri.

Certain types of human papillomaviruses have been linked to the development of carcinoma of the cervix uteri. We have analyzed 114 serum specimens from women with cervical intraepithelial neoplasia (CIN) or carcinoma of the cervix uteri for the presence of serum antibodies against purified, disrupted bovine papillomavirus (BPV). The titers of immunoglobulin A (IgA) antibodies against BPV were slightly elevated (P less than 0.025) in the sera from CIN or cervical carcinoma patients compared with the titers of 139 serum specimens from sex- and age-matched healthy controls. In contrast, both the IgG and IgM serum antibody titers against BPV were significantly decreased for CIN and cervical carcinoma patients compared with those of healthy controls (P less than 0.001 and P less than 0.005, respectively). These results suggest that the difference between IgA and IgG or IgM antibodies to papillomavirus group-specific antigens may represent interesting serological parameters that could possibly be used in the epidemiologic study of women at risk for CIN.     

Serum antibody in Actinobacillus actinomycetemcomitans-infected patients with periodontal disease

This study was designed to (i) delineate the characteristics of serum antibody responses to Actinobacillus actinomycetemcomitans in patients with periodontitis who are infected with A. actinomycetemcomitans; irrespective of disease classification; (ii) assess the relationship of the elevated antibody levels to colonization of the oral cavity by A. actinomycetemcomitans; and (iii) describe the serotype distribution of A. actinomycetemcomitans and antibodies to the microorganism in infected patients with various clinical classifications. To compare the levels of various isotype-specific antibodies to the different antigens, studies were performed that allowed quantitation of each isotype-specific antibody in a human reference standard. By using this reference standard, it was shown that the levels of immunoglobulin G (IgG), IgM, and IgA responses to A. actinomycetemcomitans were similar among the infected patients, irrespective of disease classification. Also, we demonstrated that the serum antibody response to serotype b was quantitatively greater in all isotypes. Our findings indicate that b was the most frequent A. actinomycetemcomitans serotype detected in the patients and appears to be capable of initiating a substantial serum IgG antibody response that may contain cross-reactive antibodies to other serotypes of A. actinomycetemcomitans. Generally, in cases in which the response to a single serotype was elevated, only that type of A. actinomycetemcomitans was detected in the plaque. Individuals exhibiting elevated antibodies to multiple serotypes were most consistently colonized by the serotype b microorganism. This study represents the first report detailing the distribution of IgG subclass antibodies to A. actinomycetemcomitans in periodontal disease. The results demonstrated that the primary responses of patients with periodontitis to A. actinomycetemcomitans were of the IgG1 and IgG3 subclasses, which is consistent with elicited responses to protein antigens. In contrast, the primary subclass response in normal subjects was limited to the IgG2 subclass and may represent broader cross-reactivity to polysaccharide antigens-lipopolysaccharide from the bacteria.