Heterogeneity of the humoral immune response following <Emphasis Type="Italic">Staphylococcus aureus</Emphasis> bacteremia

Expanding knowledge on the humoral immune response in Staphylococcus aureus-infected patients is a mandatory step in the development of vaccines and immunotherapies. Here, we present novel insights into the antibody responses following S. aureus bacteremia. Fifteen bacteremic patients were followed extensively from diagnosis onwards (median 29 days, range 9–74). S. aureus strains (median 3, range 1–6) and serial serum samples (median 16, range 6–27) were collected. Strains were genotyped by pulsed-field gel electrophoresis (PFGE) and genes encoding 19 staphylococcal proteins were detected by polymerase chain reaction (PCR). The levels of IgG, IgA, and IgM directed to these proteins were determined using bead-based flow cytometry. All strains isolated from individual patients were PFGE-identical. The genes encoding clumping factor (Clf) A, ClfB, and iron-responsive surface-determinant (Isd) A were detected in all isolates. Antigen-specific IgG levels increased more frequently than IgA or IgM levels. In individual patients, different proteins induced an immune response and the dynamics clearly differed. Anti-ClfB, anti-IsdH, and anti-fibronectin-binding protein A IgG levels increased in 7 of 13 adult patients (p < 0.05). The anti-IsdA IgG level increased in 12 patients (initial to peak level: 1.13–10.72 fold; p < 0.01). Peak level was reached 7–37 days after diagnosis. In a bacteremic 5-day-old newborn, antistaphylococcal IgG levels declined from diagnosis onwards. In conclusion, each bacteremic patient develops a unique immune response directed to different staphylococcal proteins. Therefore, vaccines should be based on multiple components. IsdA is immunogenic and, therefore, produced in nearly all bacteremic patients. This suggests that IsdA might be a useful component of a multivalent staphylococcal vaccine.     

Natural antibodies against several pneumococcal virulence proteins in children during the pre-pneumococcal-vaccine era: the generation R study

The currently available pneumococcal vaccines do not protect against all serotypes of Streptococcus pneumoniae. A shift toward nonvaccine serotypes causing colonization and invasive disease has occurred, and studies on protein-based vaccines have been undertaken. We assessed the association between specific antibodies against pneumococcal virulence proteins and colonization and respiratory tract infections (RTIs). Additionally, we assessed the extent to which colonization induces a humoral immune response. Nasopharyngeal swabs collected from children at 1.5, 6, 14, and 24 months of age were cultured for pneumococcus. Serum samples were obtained at birth and at 6, 14, and 24 months (n = 57 children providing 177 serum samples). Data were collected prior to the pneumococcal vaccine era. IgG, IgA, and IgM levels against 17 pneumococcal protein vaccine candidates were measured using a bead-based flow cytometry technique (xMAP; Luminex Corporation). Information regarding RTIs was questionnaire derived. Levels of IgG against all proteins were high in cord blood, decreased in the first 6 months and increased again thereafter, in contrast to the course of IgA and IgM levels. Specific antibodies were induced upon colonization. Increased levels of IgG against BVH-3, NanA, and SP1003 at 6 months, NanA, PpmA, PsaA, SlrA, SP0189, and SP1003 at 14 months, and SlrA at 24 months were associated with a decreased number of RTIs in the third year of life but not with colonization. Maternal antipneumococcal antibodies did not protect against pneumococcal colonization and infection. Certain antibodies against pneumococcal virulence proteins, some of which are induced by colonization, are associated with a decreased number of RTIs in children. This should be taken into account in future pneumococcal vaccine studies.     

Higher levels of mucosal antibody to pneumococcal vaccine candidate proteins are associated with reduced acute otitis media caused by Streptococcus pneumoniae in young children

Mucosal immunity has a crucial role in controlling human respiratory tract infections. This study characterizes the naturally acquired mucosal antibody levels to three Streptococcus pneumoniae (Spn) protein antigens, pneumococcal histidine triad protein D (PhtD), pneumococcal choline binding protein A (PcpA), and pneumolysin (Ply), and assesses the association of the mucosal antibody levels with occurrence of acute otitis media (AOM) caused by Spn. Both nasopharyngeal (NP) immunoglobulin G (IgG) and IgA levels to all three proteins slightly decreased in children from 6 to 9 months of age and then gradually increased through 24 months of age. Spn NP colonization was associated with higher mucosal antibody levels to all three proteins. However, children with Spn AOM had 5–8-fold lower IgG and 3–6-fold lower IgA levels to the three proteins than children without AOM but asymptomatically colonized with Spn. Antigen-specific antibody levels in the middle ear fluid (MEF) were correlated with antibody levels in the NP. Children with AOM caused by Spn had lower antibody levels in both the MEF and NP than children with AOM caused by other pathogens. These results indicate that higher naturally acquired mucosal antibody levels to PhtD, PcpA and Ply are associated with reduced AOM caused by Spn.     

Role of Cervicovaginal Antibody in the Pathogenesis of Recurrent Urinary Tract Infection in Women

Introital colonization with Enterobacteriaceae is considered to be one of the principal predisposing factors to recurrent urinary tract infections (UTI) in adult females. One proposed mechanism allowing introital colonization in these patients is the absence of local cervicovaginal antibody. To test this hypothesis, we examined cervicovaginal washings from 22 patients with a history of recurrent UTI and 29 normal controls with no history of UTI for specific local antibody by using indirect immunofluorescence. No significant difference in antibody was found in these populations. Fourteen percent (3/22) of the patients had antibody to their introital Escherichia coli and 34% (10/29) of the controls had antibody to their fecal E. coli. Consequently, a sensitive radioimmunoassay technique was developed to detect cervicovaginal antibody. A solid phase was prepared by coupling to Sepharose 4B a pool of eight serogroups of E. coli which are frequently implicated in UTI. Serial dilutions of cervicovaginal washings were reacted with the solid phase, and the absorbed anti-E. coli antibodies were detected by the uptake of ¹²⁵I-labeled anti-human immunoglobulin G (IgG) or anti-human IgA. The antibody levels were quantitated by interpolation on a standard curve prepared by using immunospecifically purified human anti-E. coli antibodies. IgG and IgA levels were measured in washings from 10 colonized patients, 13 non-colonized patients, and 12 controls. There were no significant differences in IgG and IgA levels in cervicovaginal washings among the three groups. In these studies, introital colonization was not related to cervicovaginal antibody.     

IgG4 Subclass-Specific Responses to Staphylococcus aureus Antigens Shed New Light on Host-Pathogen Interaction

IgG4 responses are considered indicative for long-term or repeated exposure to particular antigens. Therefore, studying IgG4-specific antibody responses against Staphylococcus aureus might generate new insights into the respective host-pathogen interactions and the microbial virulence factors involved. Using a bead-based flow cytometry assay, we determined total IgG (IgGt), IgG1, and IgG4 antibody responses to 40 different S. aureus virulence factors in sera from healthy persistent nasal carriers, healthy persistent noncarriers, and patients with various staphylococcal infections from three distinct countries. IgGt responses were detected against all tested antigens. These were mostly IgG1 responses. In contrast, IgG4 antibodies were detected to alpha-toxin, chemotaxis inhibitory protein of S. aureus (CHIPS), exfoliative toxins A and B (ETA and -B), HlgB, IsdA, LukD, -E, -F, and -S, staphylococcal complement inhibitor (SCIN), staphylococcal enterotoxin C (SEC), staphylococcal superantigen-like proteins 1, 3, 5, and 9 (SSL1, -3, -5, and -9), and toxic shock syndrome toxin 1 (TSST-1) only. Large interpatient variability was observed, and the type of infection or geographical location did not reveal conserved patterns of response. As persistent S. aureus carriers trended toward IgG4 responses to a larger number of antigens than persistent noncarriers, we also investigated sera from patients with epidermolysis bullosa (EB), a genetic blistering disease associated with high S. aureus carriage rates. EB patients responded immunologically to significantly more antigens than noncarriers and trended toward even more responses than carriers. Altogether, we conclude that the IgG4 responses against a restricted panel of staphylococcal antigens consisting primarily of immune modulators and particular toxins indicate important roles for these virulence factors in staphylococcal pathogen-host interactions, such as chronicity of colonization and/or (subclinical) infections.     

Humoral and cellular immune parameters in untreated and phenytoin- or carbamazepine-treated epileptic patients

The peripheral blood lymphocyte subsets, serum immunoglobulins (Ig A, G, M), and C3 and C4 complement protein concentrations were determined in 40 healthy subjects, 30 phenytoin-treated, 22 carbamazepine-treated and 38 untreated epileptic patients. The levels of B-lymphocytes, IgM and C3 complement proteins were found to be significantly higher in untreated epileptics than in healthy controls (P<0.01, P<0.02 and P<0.05, respectively). The absolute number of B-lymphocytes appeared to be unaffected by phenytoin or carbamazepine treatment; however, IgM levels were significantly lower in carbamazepine-treated patients than both epileptic (P<0.01) and healthy (P<0.05) controls. Phenytoin-treated patients had a significant reduction in the mean IgA and IgG levels compared to healthy and epileptic controls (P<0.05). With both drug treatments, significantly lower T-suppressor lymphocyte counts and thus higher T-helper to T-suppressor lymphocyte ratios were observed with respect to healthy and epileptic controls. Our results demonstrate that while phenytoin decreases serum IgA and IgG levels, carbamazepine reduces IgM levels significantly, and untreated epileptics show immune profiles significantly different to those of healthy subjects, suggesting that epilepsy per se may be associated with certain immune aberrations induced by antiepileptic drugs.     

Unmedicated,remitted patients with major depression have decreased serum immunoglobulin A

Patents with major depression have evidence of a proinflammatory state with consistent elevations in acute phase proteins and in the levels of inflammatory mediators such as interleukin-6 and tumor necrosis factor-α. We report here a study of the serum levels of immunoglobulin A (IgA) in medication-free patients with major depression in the remitted state (ruMDD). Selective IgA deficiency is the most common form of immunoglobulin abnormality, and is often associated with a higher than expected incidence of proinflammatory and autoimmune phenomena. We measured serum IgG, IgM, and IgA in 28 ruMDD patients and 27 healthy subjects (Ctrl) at 0 (pretreatment), 7, and 24 h following sham depletion and tryptophan (TrpD) depletion conducted at least 8 days apart under balanced, randomized, blinded conditions. Immunoglobulins were measured by automated immunonephelometry. Data were analyzed by repeated measures ANOVA with diagnosis as a fixed effect and drug (TrpD vs. sham), and time as repeated measures factors. Serum IgA was consistently lower in ruMDD patients vs. Ctrl at all time points examined (p < 0.04 for main effect of diagnosis). Serum IgG and IgM levels did not show significant differences by diagnosis. Medication-free patients with major depression in the remitted state have a significant reduction in serum IgA levels measured on multiple occasions. In the light of the fact that IgA serves many immunomodulatory, anti-inflammatory roles, this finding supports the concept that major depressive illness represents a proinflammatory state.     

Humoral and Cellular Immunity in Children with Mycoplasma pneumoniae Infection: a 1-Year Prospective Study

To determine whether children have persistent abnormalities in cellular and humoral immunity development after acute Mycoplasma pneumoniae infection, serum immunoglobulin G (IgG), IgA, IgM, and IgE levels and lymphocyte phenotypes were determined. There were no changes in the levels of IgG, IgM, IgA, or CD4⁺ or CD19⁺ lymphocytes that were measured in M. pneumoniae-positive patients after 3 months or after 12 months, but there were increases in these in M. pneumoniae-negative patients. Serum IgE increased in M. pneumoniae-positive patients. We have shown alterations in immunity development after M. pneumoniae infection.     

Corticosteroid effect on immunoglobulins

The corticosteroid (prednisone) effect on serum immunoglobulins in 9 atopic asthmatic patients who required corticosteroids for the control of asthma was evaluated. Serum immunoglobulins were determined before corticosteroids were administered, an average of 15 days while on corticosteroids, and again an average of 22 days after corticosteroids were discontinued. While on corticosteroids (averaging 16.8 mg prednisone daily) for 15 days, mean serum IgG was significantly decreased (?22%, p ≤ 0.01), mean serum IgA tended to be decreased (?10%), and mean serum IgM was essentially unchanged. Serum IgE was initially significantly increased (p < 0.01) when compared to levels of other serum immunoglobulins (IgG,A,M). An average of 22 days after corticosteroids were discontinued, mean serum IgG was still significantly decreased (p < 0.05), and mean serum IgA again tended to be decreased. Serum IgM remained unchanged and mean serum IgE now was significantly decreased (p < 0.01). Corticosteroids appear to have a significant effect on levels of some serum immunoglobulins.     

Reduced tetanus antibody titers in overweight children

Under-nutrition impairs immune responses, but far less is known about the impact of over-nutrition, such as obesity, on the response to vaccines. We measured the effect of childhood overweight status on inflammatory mediators, circulating immunoglobulins and tetanus antibodies in fifteen overweight children (BMI > 85 age-adjusted percentile) and 15 age-matched normal weight controls. Fitness was measured by a progressive ramp type exercise test. Lean body mass (LBM) and fat mass were determined by DXA. Tumor necrosis factor-a (TNF-a), interleukin-6 (IL-6), interleukin-1 β (IL-1β) and interleukin-1 receptor antagonist (IL-1ra) were used to assess the inflammatory status; and circulating immunoglobulins (IgM, IgA, IgG and IgG subclasses) and specific IgG titer to tetanus were used to assess humoral immunity. Overweight children had higher LBM and percent fat mass, and lower peak VO₂ normalized to body weight. IL-6 was significantly higher in the obese children (2.6 ± 0.3 vs. 1.3 ± 0.3 pg/ml, in overweight and normal weight children, respectively; p < 0.05). No significant differences were found in TNF-a, IL-1β and IL-1ra between the groups. No significant differences were found in immunoglobulin levels (IgM, IgA, IgG and IgG subclasses) between the groups. Anti-tetanus IgG antibodies were significantly lower in the overweight children compared to normal weight controls (2.4 ± 0.6 vs. 4.2 ± 0.5 IU/ml, in overweight and normal weight children, respectively; p < 0.05). The reduced specific antibody response to tetanus in obese children and adolescent might be due to mechanical factors such as lower relative vaccination dose, or reduced absorption from the injection site due to increased adipose tissue, or related to reduce immune response due to the chronic low grade inflammation expressed by the higher levels of IL-6.     

High levels of immunoglobulin E and a continuous increase in immunoglobulin G and immunoglobulin M by age in children with newly diagnosed type 1 diabetes

The incidence of type 1 diabetes (T1D) is increasing, either because of environmental factors accelerating onset of the disease or because of inducement of autoimmune diabetes in children who previously were at lower risk. High levels of immunoglobulin (Ig), specifically, IgM and IgA, and a low level of IgG were reported in adult patients; however no studies have analyzed the increasing incidence in relation to Ig levels. Our aim was to describe Ig in children newly diagnosed with diabetes and in their healthy siblings. Children with T1D expressed significantly lower IgG (p < 0.01) and higher IgA levels (p = 0.045), whereas no differences in IgE or IgM (p > 0.5) levels were found. Age-specific levels were unchanged over a 9-year period. In patients and siblings IgG, IgA and IgE increased by age (p < 0.001); which was in contrast to IgM (p > 0.05). The continued increase in IgG levels by age indicates that adult levels are reached later than in previously studied cohorts, thereby indicating a slower maturation of the immune system.     

Rapid fractionation of serum immunoglobulins by high pressure liquid gel permeation chromatography. Application to routine serologic procedures

High pressure liquid chromatography (HPLC) was applied to separation of IgM from IgG and IgA for the detection of virus-specific antibodies by routine serologic methods. Serum samples of 250 μl were fractionated on a HPLC protein column after filtration for use in rubella haemagglutination inhibition after preabsorption with kaolin. The protein fractions were examined for IgM, IgG and IgA content and for cross contamination.The relative recovery after kaolin absorption was satisfactory: IgM > 60%, IgG > 90%, IgA > 90%. The immunoglobulin M was well separated. IgG/IgA contamination of the fraction was < 0.2%/ < 0.5%. The IgM and IgG fractions were used without further treatment in haemagglutination inhibition. complement fixation and enzyme-linked immunosorbent assay.Highly specific results in the diagnosis of acute viral diseases (Rubella, Herpes zoster, cytomegalovirus) and Mycoplasma pneumoniae were obtained.     

Kappa/Lambda Ratios In IgG,IgA and IgM of Cerebrospinal Fluid and of Sera in Patients with Multiple Sclerosis

Kappa/lambda (κ/λ) ratios of each immunoglobulin, i.e. IgG, IgA and IgM in cerebrospinal fluid (CSF) and in sera of patients with multiple sclerosis (MS) were analysed by sandwich enzyme linked immunosorbent assay. In CSF κ/λ ratios of IgG of MS patients were significantly (p < 0.05) higher than those of normal controls, whereas the values of IgA and IgM did not differ significantly from those of normal controls. In sera κ/λ ratios of IgG, IgA and IgM did not differ significantly from those of normal controls. Our results suggest that in MS patients abnormal κ/λ ratios are also restricted to IgG components in CSF, as oligoclonal IgG bands are.     

Serum IgG, IgA, IgM, and IgE levels and allergy in Filipino children in the United States

The serum levels of IgE, IgG, IgA, and IgM of 27 American-born Filipino children 5 to 17 years of age were measured and found to be significantly higher than those of a control group of 24 Caucasian children of similar age distribution and attending the same general pediatric clinics. The geometric mean of serum IgE of the Filipinos was 227 U. per milliliter and of the Caucasians, 69 U. per milliliter (p < 0.01). The geometric means of other serum immunoglobulin levels of the Filipinos by comparison with the Caucasians were: IgG, 1,303 and 1,010 mg. per 100 ml. (p < 0.01); IgA, 195 and 120 mg. per 100 ml. (p < 0.001); and IgM, 141 and 92 mg. per 100 ml. (p < 0.02), respectively. The incidence of atopic disease was higher in the Filipino study group (48 per cent) than in the Caucasian control group (25 per cent); eczema was especially prevalent in the Filipino group. Elevated serum IgE levels were associated with atopic disease in both racial groups; however, there was no correlation between serum level of IgG, IgA, or IgM and atopy.     

Nasopharyngeal colonization elicits antibody responses to staphylococcal and pneumococcal proteins that are not associated with a reduced risk of subsequent carriage

Knowledge of the immunological correlates of Staphylococcus aureus and Streptococcus pneumoniae colonization is required for the search for future protein vaccines. We evaluated natural antibody levels against pneumococcal and staphylococcal proteins in relation to previous bacterial colonization with both pathogens. In a randomized controlled trial, nasopharyngeal samples were obtained from children at 1.5, 6, 12, 18, and 24 months and cultured for S. aureus and S. pneumoniae. Approximately 50% of the children were PCV7 vaccinated. Serum IgG against 18 pneumococcal and 40 staphylococcal proteins was semiquantified by Luminex technology from 111 12 month olds and 158 24 month olds. Previous culture-proven S. aureus colonization was associated with higher IgG levels against 6/40 staphylococcal proteins (ClfB, ClfA, Efb, CHIPS, LukD, and LukF [P ≤ 0.001]) compared to noncarriers. Previous pneumococcal colonization was associated with increased IgG levels against 12/18 pneumococcal proteins compared to noncarriers (P ≤ 0.003). Increasing age was associated with higher levels of antibodies to most pneumococcal proteins and lower levels of antibodies to over half the staphylococcal proteins, reflecting natural colonization dynamics. Anti-S. pneumoniae and anti-S. aureus protein antibodies at the age of 12 months were not negatively correlated with subsequent colonization with the homologous species in the following year and did not differ between PCV7-vaccinated and nonvaccinated children. Colonization with S. aureus and S. pneumoniae induces serum IgG against many proteins, predominantly proteins with immune-modulating functions, irrespective of PCV7 vaccination. None of them appeared to be protective against new acquisition with both pathogens, possibly due to the polymorphic nature of those proteins in the circulating bacterial population.     

Immunoblotting analysis of IgA and IgM antibody to human immunodeficiency virus type 1 (HIV-1) polypeptides in seropositive infants

Seventy infants born to human immunodeficiency virus type 1 (HIV-1) seropositive mothers were studied for specific antibody (IgA, IgM and IgG) production and the presence of active infection (detectable level of virus in peripheral blood lymphocytes). Among these children, followed for up to 15–40 months after birth, 11 presented unequivocal signs of HIV-1 infection (persistent p24 antigenemia and/or positive virus isolation). Analysis of sera by immunoblotting showed that IgA antibody to HIV-1 p24 core protein, alone or associated with envelope glycoproteins (gp120, gp41), was present in the majority of infected babies (7 of 11), while IgM was found in a lower percentage of cases (4 of 11). No IgA and or IgM antibody to HIV-1 was ever found in babies, born to seropositive mothers, who seroreverted after birth or in the control group enrolled in this study. Our results indicate that immunoblotting analysis of IgA antibody to HIV-1 polypeptides may represent a useful complementary prognostic marker in children born to HIV-1 seropositive mothers.     

Measurement of antirotavirus IgM/IgA/IgG responses in the serum samples of Indian children following rotavirus diarrhoea and their mothers

Rotavirus specific, serum IgM/IgA/IgG levels among hospitalized children and their respective mothers were determined. Children were grouped as having rotavirus diarrhoea (RVD) and non-rotavirus diarrhoea (NRVD) on the basis of fecal excretion measured by ELISA and RT-PCR. Although IgM seropositivity was observed among children of both the groups, it was significantly higher in the acute as well as convalescent phase serum samples (P < 0.05 for both) of RVD group. Five out of ten acute sera from the NRVD group were positive for IgM and seven showed IgA/IgG seroconversion indicating rotavirus infection among these children in the past. It was noted that, three out of 24 mothers' sera from RVD group, showed presence of IgM in the serum collected during convalescence of their children. The observation suggests, subclinical rotavirus infection among mothers probably contacted from their children. This is supported by the seroconversion for IgA/IgG among these three mothers. Such a phenomenon was not noticed among the mothers from NRVD group. In general, IgA positivity did not vary significantly among the children from both the groups. IgA seropositivity was significantly higher (P < 0.001) from children of RVD group as compared to healthy group of children following rotavirus infection. From RVD group, all the child patients and 12 mothers out of 24 (50%) showed IgA/IgG seroconversion. None of the mothers from NRVD group showed seroconversion. Serum samples of healthy children and adults, showed IgM positivity at equal level (10%), but a significant difference (P < 0.01) was observed in IgA positivity. In conclusion, subclinical transmission of rotavirus infection from children to their mothers may occur. Seroconversion alone cannot be considered as a marker of rotavirus diarrhoea in children. Moreover, about 40-50% of subjects lacked rotavirus specific IgA at protective levels, making them susceptible to rotavirus infection.     

Plasma immunoglobulin concentrations in a West African (Gambian) community and in a group of healthy British adults

Plasma concentrations of IgG, IgA, IgM and IgD of 1123 members of a native West African (Gambian) community and of ninety-one British adults were measured using a single radial diffusion technique. The African plasmas showed changes of immunoglobulin concentration with age which were characteristic for each class.Gambian children attained adult levels of IgG by about the 5th year of age. Mean IgG concentration in Gambian adults was approximately twice that of the British adults.IgA was not detected in Gambian children in the first few days of life. British and Gambian adults showed a similar broad range of IgA concentrations, and in Gambians the range broadened progressively with increasing age.IgM was detected in all Gambian sera, including that from the youngest children. Values rose rapidly during the first 3 months of life. In Gambian adults a broad range of values was found, with higher values becoming more frequent in the elderly. IgM levels in some Gambian sera were conspicuously increased compared with the British sera, but the anticipated increase of 19S proteins in the ultra-centrifuge was not found. High IgM levels were not associated with evidence of infection with Trypanosoma gambiense, nor were the findings typical of Walden-ström''s macroglobulinaemia.IgD was not detected in Gambian children less than 2 months of age, but a broad range of values was found in childhood and adolescence. In adults higher levels occurred less frequently and the distribution of levels was similar to that of the British population.The significance of these findings is discussed.     

Reduced tetanus antibody titers in overweight children

Under-nutrition impairs immune responses, but far less is known about the impact of over-nutrition, such as obesity, on the response to vaccines. We measured the effect of childhood overweight status on inflammatory mediators, circulating immunoglobulins and tetanus antibodies in fifteen overweight children (BMI > 85 age-adjusted percentile) and 15 age-matched normal weight controls. Fitness was measured by a progressive ramp type exercise test. Lean body mass (LBM) and fat mass were determined by DXA. Tumor necrosis factor-a (TNF-a), interleukin-6 (IL-6), interleukin-1 beta (IL-1beta) and interleukin-1 receptor antagonist (IL-1ra) were used to assess the inflammatory status; and circulating immunoglobulins (IgM, IgA, IgG and IgG subclasses) and specific IgG titer to tetanus were used to assess humoral immunity. Overweight children had higher LBM and percent fat mass, and lower peak VO2 normalized to body weight. IL-6 was significantly higher in the obese children (2.6 +/- 0.3 vs. 1.3 +/- 0.3 pg/ml, in overweight and normal weight children, respectively; p < 0.05). No significant differences were found in TNF-a, IL-1beta and IL-1ra between the groups. No significant differences were found in immunoglobulin levels (IgM, IgA, IgG and IgG subclasses) between the groups. Anti-tetanus IgG antibodies were significantly lower in the overweight children compared to normal weight controls (2.4 +/- 0.6 vs. 4.2 +/- 0.5 IU/ml, in overweight and normal weight children, respectively; p < 0.05). The reduced specific antibody response to tetanus in obese children and adolescent might be due to mechanical factors such as lower relative vaccination dose, or reduced absorption from the injection site due to increased adipose tissue, or related to reduce immune response due to the chronic low grade inflammation expressed by the higher levels of IL-6.