Serum IgG Antibody Levels Research Articles

ANTIPYRETIC, PARASITOLOGIC, AND IMMUNOLOGIC EFFECTS OF COMBINING SULFADOXINE/PYRIMETHAMINE WITH CHLOROQUINE OR PARACETAMOL FOR TREATING UNCOMPLICATED PLASMODIUM FALCIPARUM MALARIA

Sulfadoxine/pyrimethamine (SP) is increasingly used against malaria in sub-Saharan Africa because of chloroquine resistance. However, chloroquine may have a beneficial antipyretic effect. We therefore compared the combination of SP plus chloroquine, chloroquine alone, SP alone, and SP plus paracetamol in the treatment of uncomplicated Plasmodium falciparum malaria in 175 Tanzanian children (1-4 years old) in a randomized trial. Outcome variables were axillary temperatures every six hours, daily parasitemias, and serum levels of IgG antibodies to P. falciparum. Lower mean temperatures (6-48 hours) were achieved with SP plus chloroquine or paracetamol than with SP alone (P < 0.001) or chloroquine alone (P < 0.05). All three SP-treated groups showed high and similar parasite reduction (0-48 hours), whereas treatment with chloroquine alone was much less effective. Levels of IgG antibodies to P. falciparum increased significantly (P < 0.001) and similarly in the four treatment groups between days 0, 2, and 3. Thus, the addition of chloroquine or paracetamol to SP improved the clinical outcome, but did not affect the parasitologic response or antibody production.

Induction of suppressor cells following mucosal presentation of Actinomyces viscosus in mice.

Mucosal presentation of Actinomyces viscosus results in antigen-specific systemic immune suppression, known as oral tolerance. The aim of the present study was to determine the mechanism by which this oral tolerance is induced. DBA/2 mice were gastrically immunized with A. viscosus. Serum, Peyer's patch (PP) and spleen cells were transferred to syngeneic recipients which were then systemically challenged with the sameiA. viscosus strain. To determine antigen-specificity of cells from gastrically immunized mice, recipients which received immune spleen cells were also challenged with Porphyromonas gingivalis. One week after the last systemic challenge, the delayed type hypersensitivity (DTH) response was determined by footpad swelling and the level of serum IgG, IgA and IgM antibodies to A. viscosus or P. gingivalis measured by an ELISA. No suppression of DTH response or of specific serum antibodies was found in recipients which received serum from gastrically immunized mice. Systemic immune suppression to A. viscosus was observed in recipients which had been transferred with PP cells obtained 2 days but not 4 and 6 days after gastric immunization with A. viscosus. Conversely, suppressed immune response could be seen in recipients transferred with spleen cells obtained 6 days after gastric immunization. The immune response to P. gingivalis remained unaltered in mice transferred with A. viscosus-gastrically immunized cells. The results of the present study suggest that oral tolerance induced by A. viscosus may be mediated by antigen-specific suppressor cells which originate in the PP and then migrate to the spleen.

Immunogenicity and protective efficacy of orally administered recombinant Lactococcus lactis expressing surface-bound HIV Env

AbstractThis study investigates whether genetically modified orally administered Lactococcus lactis (L lactis) could be used as an HIV vaccine. L lactis is immunogenic and extremely safe when delivered orally. We created a recombinant L lactis vector expressing the envelope protein of HIV on its cell surface. Oral immunization with this vector induced high levels of HIV-specific serum IgG and fecal IgA antibodies. Cell-mediated immune responses also were generated in both the regional lymph nodes and the spleen. Dendritic cells are readily infected by L lactis and appear to play a potential role in mediating the development of these immune responses. The protective efficacy of this vaccine strategy was demonstrated by challenging mice intraperitoneally with an HIV Env–expressing vaccinia virus. Their viral loads were 350-fold lower than those of control mice. These findings support the further development of L lactis–based HIV vaccines. (Blood. 2003; 102:223-228)

Treatment of IgM antibody associated polyneuropathies using rituximab

Objectives: Polyneuropathies with associated serum IgM antibodies are often difficult to treat. Rituximab is a monoclonal antibody directed against the B cell surface membrane marker CD20. Rituximab eliminates B cells...

Multiple sclerosis and Epstein-Barr virus.

Infection with Epstein-Barr virus (EBV) has been associated with an increased risk of multiple sclerosis (MS), but the temporal relationship remains unclear. To determine whether antibodies to EBV are elevated before the onset of MS. Nested case-control study conducted among more than 3 million US military personnel with blood samples collected between 1988 and 2000 and stored in the Department of Defense Serum Repository. Cases were identified as individuals granted temporary or permanent disability because of MS. For each case (n = 83), 2 controls matched by age, sex, race/ethnicity, and dates of blood sample collection were selected. Antibodies including IgA against EBV viral capsid antigen (VCA) and IgG against VCA, nuclear antigens (EBNA complex, EBNA-1, and EBNA-2), diffuse and restricted early antigens, and cytomegalovirus. The average time between blood collection and MS onset was 4 years. The strongest predictors of MS were serum levels of IgG antibodies to VCA or EBNA complex. The risk of MS increased monotonically with these antibody titers; relative risk (RR) in persons in the highest category of VCA (> or =2560) compared with those in the lowest (< or =160) was 19.7 (95% confidence interval [CI], 2.2-174; P for trend =.004). For EBNA complex titers, the RR for those in the highest category (> or =1280) was 33.9 (95% CI, 4.1-283; P for trend <.001) vs those in the lowest category (< or =40). Similarly strong positive associations between EBV antibodies and risk of MS were already present in samples collected 5 or more years before MS onset. No association was found between cytomegalovirus antibodies and MS. These results suggest a relationship between EBV infection and development of MS.

Indigenous Greenlanders have a higher sero-prevalence of IgG antibodies to Helicobacter pylori than Danes

Objective: To assess the sero-prevalence of IgG antibodies to Helicobacter pylori (H. pylori) in Greenlanders and compare with the sero-prevalence in Caucasian Danes.Methods: 71 randomly recruited indigenous Greenlanders (29 men) with a median age of 39 years (range 22–76), living in the capital, Nuuk, and the town of Ilulissat, and participating in a population survey carried out in 1993–1994. The results were compared with those obtained in a 1983–1984 population survey in Copenhagen County, comprising 2794 Caucasian Danes (1425 men) with a median age of 41 years (range 30-60). Serum IgG antibody levels to H. pylori were determined by an indirect enzyme-linked immunosorbent assay in 1995 and categorised as negative, borderline (equivocal), or positive.Results: Greenlanders: 48.3 % of men and 45.2% of women had positive serum IgG antibody levels to H. pylori. In the entire series, 46.5% had positive IgG antibody levels, 25.4% displayed borderline antibody levels and 28.2% had negative antibody levels. There were no age, or gender differences concerning the prevalences of the three H. pylori IgG antibody subgroups. Danes: 25.6 % of men, and of women, had positive IgG antibody levels against H. pylori. In the entire series, 25.6% had positive IgG antibody levels, 19.0% displayed borderline antibody levels and 55.4% had negative antibody levels. There was no gender difference concerning the sero-prevalence of IgG antibodies, but the sero prevalence increased significantly with age. The prevalence of positive serum IgG antibodies against H. pylori was markedly higher in Greenlanders than in Danes (p <0.0001).Conclusion: Indigenous Greenlanders have a significantly higher infection rate with H. pylori than Danes. The results suggest that Greenlanders become infected with H. pylori early in life.

Implication of responses to bacterial heat shock proteins, chronic microbial infections, and dental metal allergy in patients with pustulosis palmaris et plantaris.

Pustulosis palmaris et plantaris (PPP) is a chronic relapsing skin disease characterized by sterile intraepidermal pustules and, usually, by scaly erythematous skin on the palm, soles, or both. To determine the primary pathogenic factors involved in the onset of PPP, we analyzed the implications of heat shock proteins (HSPs), which are highly conserved immunogenic proteins, chronic microbial infections including marginal and periapical periodontitis, and delayed type hypersensitivity (DTH) against dental metals examined by patch tests. We found that the titers of IgG against HSPs of Escherichia coli GroEL and Actinobacillus actinomycetemcomitans DnaJ in the sera from PPP patients were higher than those in the control group (GroEL; p < 0.05). Two patients with PPP had more than 1,000 ng/ml serum IgE level. We found that the average serum IgG antibody level against human cytomegalovirus (HCMV) in the PPP patient group was higher than that of the healthy group (p < 0.05). DTH against dental metal was found in eight of 22 PPP patients. Six of eight patients reacted against more than two metals. Replacement of dental metal with resin in these patients resulted in the disappearance or remission of PPP. These findings suggest that the immune responses to HSPs produced by oral bacteria, HCMV infection, dental metal allergy, and their combinations are etiological factors for PPP. We concluded that various kinds of examinations, including oral cavity conditions and chronic infections, are essential to determine the major etiologic factors of PPP.

Intranasal immunization with influenza vaccine and a detoxified mutant of heat labile enterotoxin from Escherichia coli (LTK63)

Groups of 10 Balb/c mice were immunized intranasally (IN) with influenza haemagglutinin (HA), and a genetically detoxified mutant of heat-labile enterotoxin from Escherichia coli (LTK63) at several different doses. IN immunization at the optimal dose combination for HA and LTK63 induced equivalent levels of serum IgG antibodies to intramuscular (IM) immunization with HA alone, and induced significantly enhanced IgA titers in nasal wash. However, haemagglutination inhibition (HI) assays showed that the IM vaccine induced approximately 10-fold higher HI titers than IN immunization with HA and LTK63. In a second study, HA and LTK63 was compared to a licensed emulsion adjuvant MF59 by the IN route. LTK63 was shown to be significantly more potent than MF59 when evaluated at the optimal dose combination with HA. Hence, the LTK63 and HA combination represents an attractive candidate for evaluation as an IN vaccine in larger animal models, or humans.

A DNA vaccine encoding a cell-surface protein antigen of Streptococcus mutans protects gnotobiotic rats from caries.

A cell-surface protein antigen (PAc) of Streptococcus mutans is considered a virulence factor because it may mediate initial attachment of Streptococcus mutans to tooth surfaces. Thus, inhibiting PAc is predicted to provide protection against caries. To develop vaccines against dental caries, we constructed a DNA vaccine, pCIA-P, which encodes two high-conservative regions of PAc. Expression of the recombinant protein was obtained in eukaryotic cells in vitro and in vivo. In this report, we provide evidence that fewer caries lesions, and high levels of PAc-specific salivary IgA antibody and serum IgG antibody, were observed in gnotobiotic rats following targeted salivary gland (TSG) administration of pCIA-P. This study shows that the recombinant DNA vaccine pCIA-P could induce protective anti-caries immune responses and that TSG immunization is a promising strategy for the inhibition of dental caries.

Mucosal and systemic antibody responses against an acellular pertussis vaccine in mice after intranasal co-administration with recombinant cholera toxin B subunit as an adjuvant

To investigate the possibility of intranasal immunization with an acellular pertussis vaccine, groups of mice were administered intranasally with aluminium-non-adsorbed pertussis toxoid (PTd; 0.5 or 5 μg) and formalin-treated filamentous hemagglutinin (fFHA; 5 μg) with and without recombinant cholera toxin B subunit (rCTB; 10 μg) as a mucosal adjuvant. At a low concentration of PTd, the following things became clear: (1) earlier and higher elevation of serum anti-PTd and anti-FHA IgG antibody titres in the presence of rCTB than in its absence, (2) higher serum anti-PTd and anti-FHA IgG antibody titres than 200 and 100 ELISA units ml −1 (EU ml −1) in all mice, respectively, in the presence of rCTB, which were obtained by calibration against a reference anti-pertussis mouse serum, and (3) in an intranasal challenge experiment with Bordetella pertussis, slightly more rapid elimination of the bacteria from the lungs of mice intranasally immunized in the presence of rCTB, suggesting the effectiveness of rCTB as a mucosal adjuvant. However, irrespective of rCTB and dose of PTd, mice which were immunized four times and sacrificed on day 35 developed high levels of anti-PTd serum IgG antibodies, high or moderate levels of anti-FHA serum IgG antibodies and mucosal anti-PTd IgA antibodies in the lungs; only a slight or no increase of anti-FHA mucosal IgA antibodies was observed in the lung. These facts suggested the immunogenicity and mucosal adjuvanticity of PTd, and therefore, the mucosal adjuvanticity of rCTB seemed to be inconspicuous. Moreover, the addition of rCTB induced higher anti-PTd serum IgE antibody responses than no addition of it depending on dose of PTd. These results show that dose of PTd included in an acellular pertussis vaccine had better be low as possible and the addition of rCTB may not be always necessary in case of this nasal vaccine alone unlike tetanus and diphtheria toxoids and hepatitis B virus vaccine reported before.

The impact of Fcγ receptors on Staphylococcus aureus infection

Antibodies are known to be an important defence mechanism of the host's immune response towards certain invading microorganisms. Earlier findings have shown that antibodies directed to certain surface molecules on Staphylococcus aureus are of importance in systemic defence against infections. To further investigate the contribution of humoral immunity during intravenously induced S. aureus septicemia and arthritis we have studied the impact of IgG Fc receptors (FcγRs). DBA/1 mice deficient for the common γ-chain (lacking the activating receptors, FcγRI, FcγRIII and FcϵRI) or the inhibitory FcγRII and corresponding littermate controls were used. We found that absence of FcγRII expression significantly increased the survival rate following severe infection with S. aureus. The FcγRII−/− infected mice showed increased levels of IL-10, elevated serum levels of IgG antibodies against clumping factor A and enhanced phagocytic capacity of granulocytes and monocytes, as compared to control mice. Deficiency in the common γ-chain (FcγRI, III and FcϵRI) did not influence the arthritogenicity nor the mortality of systemic S. aureus infection. We conclude that expression of Fcγ receptor II is of importance during S. aureus infection.

Porphyromonas gingivalis infection is associated with elevated C-reactive protein in nonobese Japanese type 2 diabetic subjects.

Coronary heart disease (CHD) is the leading cause of death among patients with type 2 diabetes. Several factors were observed to be associated with an increased risk of major manifestations of CHD. Elevated levels of C-reactive protein (CRP), although often in the healthy reference range, have been associated with increased risk of future CHD (1). We hypothesized that periodontal infection might contribute to the elevated CRP in diabetic populations, since periodontal disease has recently been declared the sixth complication of diabetes (2). Serum IgG antibody levels against several periodontal pathogens, especially against Porphyromonas gingivalis ( P. gingivalis ), are elevated …

Long-term antibody responses following human infection with Campylobacter jejuni.

Epidemiological evidence suggests prior infection of humans by Campylobacter jejuni leads to protection against disease following further exposure. It is known that infections elicit strong antibody responses following the onset of disease and that antibody levels are elevated in putatively immune populations. To determine if systemic and mucosal antibodies induced by a confirmed infection remain at elevated levels for prolonged periods, repeat serum, saliva and urine samples were taken from campylobacter patients from 1 week and up to a year postinfection. Antibodies were monitored by ELISAs using three different antigen preparations: acid-glycine extracts (AE) of C. jejuni strain 81116 and an aflagellate mutant (R2), and a whole-cell R2 sonicate, and by Western blotting. Levels of serum IgG antibodies against 81116AE and R2 sonicate, but not R2AE, remained significantly raised over time when compared to a comparison population. Serum anti-sonicate IgA antibody levels were initially significantly raised but decreased over time to levels similar to the comparison group. There were no significant differences in levels of salivary IgA against the AEs. Anti-sonicate salivary IgA and IgG levels were initially significantly higher than in the comparison group. Both declined over time but the IgG levels remained significantly higher. Significant correlations were seen between serum IgG levels and age and duration of illness. Serum antibodies against flagellin, 40 kDa and 29 kDa antigens were still detectable in most patients up to a year postinfection, as were salivary antibodies to flagellin, the major outer-membrane protein and a 40 kDa antigen.

Characterization of protective immune responses induced by nasal influenza vaccine containing mutant cholera toxin as a safe adjuvant (CT112K)

Immune responses induced by a nasal influenza vaccine with a mutant cholera toxin (CT112K), known to be a safe adjuvant, were characterized in BALB/c mice to confirm the most suitable regimen of this vaccine for humans. Mice received a primary intranasal administration of the adjuvant (0.1 μg)-combined PR8 vaccine (0.1 μg) and a secondary administration of the PR8 vaccine alone (0.1 μg) 4 weeks later. Two weeks after the secondary immunization, the mice were infected with a nonlethal or a lethal dose of PR8 viruses. Nasal and lung wash virus titers 1 or 3 days after infection indicated that complete protection could be provided by secondary immune responses, which had an immediate effect of preventing infection 2 weeks after the secondary immunization. In this two-dose regimen, high levels of secondary IgA, IgG and IgM antibody-forming cell (AFC) responses were induced in the nasal-associated lymphoid tissue and the spleen. In parallel with the AFC responses, high levels of nasal wash anti-PR8 HA IgA, and lung and serum IgG antibody (Ab) responses were induced 2 weeks after the secondary immunization. The two-dose regimen also induced accelerated delayed-type hypersensitivity responses, which exhibited almost the same peak height as that in the case of the primary response. In addition, the two-dose regimen induced a low memory cell activity of cytotoxic T lymphocytes, detected by in vitro culture of spleen cells. Thus, the immediate effect of preventing infection was mainly provided by the secondary Ab responses. Moreover, the levels of nasal wash IgA Abs correlated well with cross-protection against infection with variant viruses in the upper respiratory tract (RT). These results suggest that the major protective factors among Ab and T cell-mediated immune responses, which are induced by the two-dose regimen using CT112K-combined vaccines, are the cross-reactive IgA Abs in the upper RT and the less cross-reactive IgG Abs in the lower RT, and that the two-dose regimen is a suitable vaccination condition for humans.

Serum immunoglobulin E, IgA, and IgG antibodies to different cow's milk proteins in children with cow's milk allergy: association with prognosis and clinical manifestations.

Diverse pathogenic mechanisms elicit different clinical manifestations in cow's milk allergy (CMA). Our aim was to determine the concentration of serum immunoglobulin levels to different cow's milk proteins in patients with CMA and to determine how these values were related to clinical symptoms and prognosis. Fifty children (mean age 10.9 months, range: 1-34 months) with previously confirmed CMA were enrolled in this study. All had various clinical manifestations of CMA, including gastrointestinal, skin, and respiratory symptoms. At the diagnosis of CMA the serum total and the milk-specific immunoglobulin (Ig)E values were measured by enzyme immunoassay and fluoroimmunoassay, respectively, while the relative levels of serum IgA and IgG antibodies against different cow's milk proteins were determined by a sensitive enzyme-linked immunosorbent assay (ELISA). The results were compared to those of 30 non-atopic age-matched control children. On average, after 9.2 months (range 2-31 months) on a milk-free diet, a repeated challenge was performed in 38 children. At the re-challenge, 12 patients had clinical symptoms while the remaining 26 children were symptom-free. The IgG antibody level to bovine serum albumin (BSA) was significantly lower in the patients than in the controls (median: 0.36 vs. 2.94, p < 0.01). There was a close correlation among all individual IgA and IgG antibodies to different cow's milk proteins. The anti-alpha-casein IgG level (of 2.10) in children with a positive reaction at the re-challenge was significantly higher than in those with a negative reaction (0.89) (p < 0.05). The total IgE serum concentration was also significantly higher in those who had symptoms at the re-challenge compared to those who did not have any reaction at this time (22.9 vs. 6.8 kU/l, geometric mean, p < 0.02). There was no association between the clinical manifestations and the IgG and IgA antibody levels to the cow's milk proteins studied, except for the anti-BSA IgA level, which was higher in patients with gastrointestinal symptoms. The serum total IgE and anti-alpha-casein IgG levels could have prognostic values; their increase at the beginning of the disease may indicate the development of tolerance to cow's milk only at a later age and after a longer duration of CMA. However, as there is considerable overlap among the values observed in different groups of patients, there is a limitation of these tests for predicting the prognosis.

Recognition of the carbohydrate modifications to the RgpA protease of Porphyromonas gingivalis by periodontal patient serum IgG.

Periodontal infections by Porphyromonas gingivalis are associated with a sustained systemic IgG antibody response and elevations in local antibody synthesis to this organism. One of the targets of this response is a protease, RgpAcat, which is an important virulence determinant of this organism. Recently, we demonstrated that this molecule is glycosylated and that the glycan chains are immunologically related to P. gingivalis lipopolysaccharide (LPS) (Curtis et al., Infect Immun 1999;62:3816-3823). In the present study, we examined the role of these glycan additions in the immune recognition of RgpAcat, by sera from adult periodontal patients (n = 25). Serum IgG antibody levels to P. gingivalis W50, RgpAcat and LPS and to recombinant RgpA were determined by enzyme-linked immunosorbant assay (ELISA). No correlation was observed between the antibody levels to RgpAcat from P. gingivalis and the recombinant form of this enzyme expressed in Escherichia coli. However, a strong association was found between the recognition of LPS and the wild-type enzyme (R = 0.8926; p = 0.0005). Incorporation of LPS into the ELISA led to a significant reduction (mean 25%; range 0.8-43%, SD = 15; p < 0.05) in the recognition of RgpAcat, but had no effect on the recognition of control antigens. Deglycosylation of RgpAcat led to the abolition of immune recognition by patient serum IgG, which suggests that the glycan additions to this molecule are the principal targets of the immune response. Therefore, glycosylation of the RgpAcat protease may play an important role in immune evasion by shielding the primary structure from immune recognition.

Intranasal immunization with recombinant antigens associated with new cationic particles induces strong mucosal as well as systemic antibody and CTL responses

New cationic nanoparticles (SMBV™) were evaluated for use as a nasal vaccine delivery system for two recombinant proteins: HBsAg and β-galactosidase. Each protein was formulated with SMBV™ and intranasally administrated to non-anesthetized mice. In each model, the formulated protein induced high levels of specific serum IgG antibodies and cytotoxic T lymphocyte (CTL) responses. Moreover, specific IgA antibodies were found in nasal as well as in vaginal washes of intranasally immunized mice with the protein associated with SMBV™. In contrast, no IgG or IgA antibodies and no CTL were detected in mice immunized with free protein. The detection of a CTL response and an increase in both IgG1 and IgG2a antibodies in serum suggest that SMBV™ amplifies both Th1 and Th2 responses without modifying the Th1/Th2 profile of the immune response induced by the natural protein. These data demonstrate the high potential of SMBV™ for use as a nasal delivery system for sub-unit vaccines.

Clinical and immunological risk factors for severe disease in Japanese encephalitis

Eighty-five paediatric patients in Thailand with acute Japanese encephalitis (JE) were studied in 1987–1999 to determine risk factors present at hospital admission which were associated with severe disease. On univariate analysis, the following factors on admission were significantly associated with the combined end-point of death or a severe neurological deficit: depressed level of consciousness, elevated concentration of cerebrospinal fluid (CSF) protein, low levels of serum and CSF IgG antibody against Japanese encephalitis virus (JEV), low level of serum IgM antibody against JEV, and a serological response consistent with primary flavivirus infection. On multivariate analysis, an initial serum anti-JEV IgM < 150 U and the absence of a prior flavivirus infection, presumably dengue, remained independent risk factors for death or a severe neurological deficit. The ability to mount an early and vigorous JEV-reactive antibody response is associated with a better outcome from acute JE. An anamnestic, anti-flavivirus, immune response induced by a prior dengue virus infection can be an important means of providing this protection.

Intranasal immunization with lipoteichoic acid and cholera toxin evokes specific pharyngeal IgA and systemic IgG responses and inhibits streptococcal adherence to pharyngeal epithelial cells in mice

Objective: Streptococcus ( S.) pyogenes is common cause of acute tonsillitis. Lipoteichoic acid (LTA), which is a common constitute of the cell surface of most gram positive bacteria, is known to act as a substance of bacterial site for adherence to epithelium and antiserum to LTA is reported to inhibit bacterial attachment to epithelial cells in vitro. Cholera toxin subunit B (CT-B) is known to be a mucosal adjuvant. The purpose of this study is to investigate whether intranasal immunization with LTA and CT-B may be a possible candidate for vaccine formulation. Methods: Six-week-old male BALB/c mice were assigned to three experimental groups, mice immunized with LTA and CT-B, with LTA alone and with phosphate buffered saline (PBS) as a control. Immunizations were performed intranasally every 2 days for 2 weeks in every group. At the 21 days after immunization, sera, pharyngeal washings and pharyngeal epithelial cells were taken. The levels of serum IgG and pharyngeal IgA antibodies to LTA were measured by enzyme-linked immunosorbent assay (ELISA). The adherence rates of S. pyogenes pretreated by pharyngeal washings to pharyngeal epithelial cells from the mice were determined by in vitro adherence assay. Results: The serum anti-LTA IgG antibody levels of either mice immunized with LTA and CT-B or mice immunized with LTA alone were significantly higher than those of mice administered with PBS alone. The pharyngeal anti-LTA IgA antibody levels of the mice immunized with LTA and CT-B were significantly higher than those of either mice with LTA alone or mice with PBS alone. The streptococcal adherence rates to pharyngeal epithelial cells were significantly decreased by pretreatment with pharyngeal washings from the mice immunized with LTA and CT-B as compared with pretreatment with those from either mice with PBS or mice with LTA alone. Conclusions: These data shows that intranasal immunization with LTA and CT-B evokes a good pharyngeal IgA response as well as systemic IgG response to LTA and inhibits streptococcal adherence to pharyngeal epithelial cells, suggesting that intranasal immunization with LTA and CT-B may be an effective approach to prevent streptococcal tonsillitis.

Decreased serum and pharyngeal antibody levels specific to streptococcal lipoteichoic acid in children with recurrent tonsillitis

Objective: Streptococcus ( S.) pyogenes is a common cause of primary as well as recurrent tonsillitis (RT). Lipoteichoic acid (LTA) has been proposed as a possible candidate for vaccine formulation against streptococcal infections, because LTA is a common constituent of streptococci and the antibody to LTA inhibits bacterial attachment to epithelial cells in vitro. Streptolysin-O and streptococcal whole cell body are highly immunogenic and the antibodies to these antigens are reported to be better parameters for streptococcal infections The objective of the present study is to investigate how systemic and local immune activities against S. pyogenes may be associated with RT. Methods: Sera from 178 children with or without RT aged 1–15 years with a median age of 5 years were investigated for the levels of total immunoglobulins and antibodies specific to streptococcal antigens such as whole cell body, LTA, and streptolysin-O. Pharyngeal secretions from 67 children with or without RT aged 2–14 years with a median age of 6 years were subjects to secretory IgA (SIgA) antibody levels to streptococcal LTA. The antibodies to whole cell body and LTA were measured by enzyme-linked immunosorbent assay. Total immunoglobins and the anti-streptolysin-O antibody were assayed by nephelometry. Results: An age-matched comparison revealed that either levels of serum IgG antibody or pharyngeal SIgA antibody to streptococcal LTA at 2–5 years of age were significantly lower in RT children than in non-RT children (1.39 vs. 5.14 μg/ml, P=0.001; 10.6 vs. 29.9 units/ng/ml total SIgA, P=0.015; respectively) and correlated inversely to episodes of tonsillitis ( r=−0.242, P=0.024; r=−0.3, P=0.024; respectively). Either serum total immunoglobulin levels of IgG or IgA correlated positively to episodes of tonsillitis in children aged 2–5 years ( r=0.293, P=0.011; r=0.361, P=0.002; respectively). No difference was found on either serum levels of IgG antibody to streptococcal whole cell body or antibody to streptolysin-O between RT and non-RT children in any age-matched comparisons. High serum antibody levels to whole cell body was associated with high antibody levels to streptococcal LTA in non-RT children ( r=0.198, P<0.05), but no association was found between these antibody levels in RT children. Conclusions: Selective immunologic failure in systemic and pharyngeal antibody response to streptococcal LTA may be a potential cause of RT in young children.