Serum IgG Antibody Levels Research Articles

Antibodies to type II collagen in early rheumatoid arthritis. Correlation with disease progression

To establish that frequencies and levels of IgG antibodies to type II collagen are higher in early rheumatoid arthritis (RA), and to correlate these results with disease activity. Forty-four patients were characterized as having early RA. Patient sera obtained at initial presentation and at 12 months were tested by enzyme-linked immunosorbent assay for IgG antibodies to native and denatured type II collagen. IgG antibodies to native and denatured type II collagen were detected at initial presentation in 27% and 82% of patients, respectively, and after 12 months in 14% and 50%, respectively. The presence of antibodies to native collagen was associated with activity of RA and severity of symptoms, and loss of antibodies at 12 months was associated with initially erosive RA and the DRB1 disease susceptibility motif. Levels of serum IgG antibodies to collagen in RA decrease over time and, therefore, are not attributable simply to cartilage destruction. The presence of early positivity for these antibodies, together with the RA susceptibility motif, appears to be predictive of rapidly progressive RA.

Single dose, polymeric, microparticle-based vaccines: the influence of formulation conditions on the magnitude and duration of the immune response to a protein antigen

Ovalbumin-loaded poly(D,L-lactide co-glycolide) [OVA-loaded PLG] microparticles, produced by emulsion/solvent evaporation stimulated the production of high serum IgG antibody levels after a single subcutaneous (s.c.) administration in mice and the duration of the immune response paralleled the degradation rate of the carrier. Formulations based on slow resorbing PLG maintained relatively constant peak antibody levels for 26 weeks and high titres for over 1 year at a level approximating the peak response to the faster resorbing, OVA-loaded particles which was of lower duration. Vaccine formulations prepared by simple mixing of blank PLG microparticles and OVA exhibited low primary immune responses which were only elevated by boosting. OVA-loaded PLG microparticles exhibited a substantial surface protein component amounting to ca 40% and 60% of the total protein loading for slow resorbing and fast resorbing PLG, respectively. These findings suggest that sustained presentation of surface protein to the immune system was a major factor in the induction and long-term maintenance of high antibody titres following a single s.c. administration of OVA-loaded microparticles

Characterization of histamine releasing factors in diisocyanate-induced occupational asthma

Immunologic mechanisms contributing to diisocyanate-induced occupational asthma (OA) are poorly defined. There is a relatively low incidence of diisocyanate-specific IgE antibody responses. The frequent occurrence of delayed onset asthmatic responses in workers with diisocyanate asthma suggests a role for cellular immune mechanisms. We have shown in vitro production of antigen-specific mononuclear cell-derived histamine releasing factors (HRF) by peripheral blood mononuclear cells (PBMCs) of workers with OA. Monocyte chemoattractant protein-1 (MCP-1) and RANTES (acronym for “regulated on activation normal T expressed and secreted”) are chemokines found in PBMC supernatants that express HRF activity. Diisocyanate-exposed workers were tested for diisocyanate antigen-stimulated enhancement of HRF, MCP-1, and RANTES production in supernatants of PBMCs and for serum specific IgE and IgG antibody levels to diisocyanate antigens bound to human serum albumin (HSA). PBMCs of workers with diisocyanate OA showed significantly increased production of antigen-specific HRF activity and MCP-1 ( >300 ng/ml) compared to diisocyanate-exposed asymptomatic workers ( P < 0.05). Antigen-stimulated enhancement of MCP-1 mRNA was demonstrated by reverse-transcription PCR. RANTES mRNA and chemokine secretion (< 1 ng/ ml) was also demonstrated in PBMCs, but did not show antigen enhancement in OA workers. Hapten specificity for the diisocyanate chemical to which a patient had been exposed was demonstrated for HRF enhancement and for IgG antibody reactions, but not for IgE reactions. HRF production was demonstrated in PBMC subpopulations, including lymphocytes and purified T cells. OA subjects showed increased CD8 + cells by immunofluorescence (mean CD4 +:CD8 + = 1.2 ± 0.2). The results suggest that diisocyanate antigen enhancement of HRF and MCP-1 production are stimulated by hapten-specific T cell reactions. Since a weak association has been found between IgE antibody synthesis and induction of diisocyanate OA, the role of T cell cytokines and chemokines in the pathogenesis of OA requires further investigation.

Increased Immune and Inflammatory Responses to Dust Mite Antigen in Rats Exposed to 5 ppm NO2

Immune hypersensitivity to house dust mite antigen (HDM) is a frequent cause of respiratory allergy. The objective of this study was to determine whether exposure to NO2, a common indoor air pollutant, modulates immune responses to HDM and influences immune-mediated lung disease. Brown Norway rats were immunized ip with 100 μg semipurified antigen andBordetella pertussisadjuvant and challenged 2 weeks later with an intratracheal injection of 50 μg of a crude antigen preparation. Exposure to 5 ppm NO2for 3 hr after both immunization and challenge procedures resulted in significantly higher levels of antigen-specific serum IgE, local IgA, IgG, and IgE antibody than air controls, and increased numbers of inflammatory cells in the lungs. Lymphocyte responsiveness to antigen in the spleen and MLN was also significantly higher in NO2-exposed animals. These data show that exposure to a common air pollutant can upregulate specific immune responses and subsequent immune-mediated pulmonary inflammation.

Measles immunity and response to revaccination among secondary school children in Cumbria

The prevalence of antibody to measles virus in 759 children aged 11-18 years attending a secondary school in Cumbria was measured using a salivary IgG antibody capture assay. Serum IgG antibody levels were measured using a plaque reduction neutralization assay in subjects whose saliva was antibody negative. Vaccination histories were obtained from the child health computer and general practice record. A total of 662 pupils (87% of those tested) had detectable measles-specific IgG in saliva. Of the remaining 97, 82 provided blood samples and 29 had serum neutralizing antibody levels above 200 mIU/ml. Afer adjusting for non-participation rates, the proportion considered non-immune (no IgG in saliva and < or = 200 mIU/ml in serum) was 9% overall, ranging from 6% in vaccinated children to 20% in unvaccinated children. Measles-mumps-rubella vaccine was given to 50 children of whom 38 provided post-vaccination serum and 32 saliva samples. Thirty (79%) had a fourfold or greater rise in serum neutralizing antibody and 28 (88%) developed IgG antibody in saliva. Half of the children considered non-immune by antibody testing would have been overlooked in a selective vaccination programme targeted at those without a history of prior vaccination. A programme targeted at all school children should substantially reduce the proportion non-immune since a primary or booster response was achieved in three quarters of previously vaccinated children with low antibody levels and in all unvaccinated children. While it is feasible to screen a school-sized population for immunity to measles relatively quickly using a salivary IgG assay, a simple inexpensive field assay would need to be developed before salivary screening and selective vaccination could substitute for universal vaccination of populations at risk of measles outbreaks. The salivary IgG assay provided a sensitive measure of a booster response to vaccination.

Increased Immune and Inflammatory Responses to Dust Mite Antigen in Rats Exposed to 5 ppm NO2

Immune hypersensitivity to house dust mite antigen (HDM) is a frequent cause of respiratory allergy. The objective of this study was to determine whether exposure to NO2, a common indoor air pollutant, modulates immune responses to HDM and influences immune-mediated lung disease. Brown Norway rats were immunized ip with 100 μg semipurified antigen and Bordetella pertussis adjuvant and challenged 2 weeks later with an intratracheal injection of 50 μg of a crude antigen preparation. Exposure to 5 ppm NO2 for 3 hr after both immunization and challenge procedures resulted in significantly higher levels of antigen-specific serum IgE, local IgA, IgG, and IgE antibody than air controls, and increased numbers of inflammatory cells in the lungs. Lymphocyte responsiveness to antigen in the spleen and MLN was also significantly higher in NO2-exposed animals. These data show that exposure to a common air pollutant can upregulate specific immune responses and subsequent immune-mediated pulmonary inflammation.

Antibody responses to suspected periodontal pathogens in elderly subjects with periodontal disease

Little is known about the relationship of aging to periodontal disease. The immune response undergoes aging-related changes resulting in loss of functional capacity. The aim of this study was to investigate the relationship between levels of serum IgG antibodies against suspected periodontal pathogenic microorganisms to the presence or absence of periodontal disease in an elderly (65-75 yrs) population. From this study, we obtained information concerning: (1) the ability to differentiate elderly individuals without disease from those with disease by their levels of antibodies against periodontal pathogens and (2) which periodontal pathogen(s) triggered those responses. IgG anti- Porphyromonas gingivalis (strains W83 and 381) levels in the serum of elderly patients with severe periodontal disease were the only antibody responses measured which were elevated compared to the elderly control group of subjects with no periodontal disease. Anti- Prevotella intermedia IgG levels in both elderly patient groups were depressed compared to anti- P. intermedia levels in the young normal control subjects. Serum IgG antibody levels to six other plaque microorganisms did not differentiate between diseased and normal, elderly or young subjects. This data suggested that P. gingivalis was associated with periodontal disease in this elderly group of individuals and that those elderly individuals were able to respond with a normal IgG immune response.

The preparation, characterization and pre-clinical evaluation of an orally administered HIV-I vaccine, consisting of a branched peptide immunogen entrapped in controlled release microparticles

A microencapsulated vaccine was prepared, containing a branched peptide immunogen (200M), representing a portion of the principal neutralizing determinant of HIV-1, entrapped in poly (lactide-co-glycolide) microparticles. Following extensive in vitro characterization of the microparticles, which included assessments of particle size and size distributions, microparticle surface structure, antigen loading level and efficiency of entrapment, moisture content, the levels of residual solvent, the in vitro release rate, an assessment of antigen integrity, the product bioburden and stability during storage, the microparticles were assessed in vivo. The initial assessments undertaken, involved studies in different animal species to determine the safety and pyrogenicity of the vaccine and also the toxicity following oral administration. Once the microparticles had been shown to be safe, pyrogen free and non-toxic, they were assessed for their ability to induce serum IgG and neutralizing antibody responses in guinea pigs. Following oral immunization alone, and combined oral and subcutaneous immunization, the microparticles were shown to induce high levels of both serum IgG and neutralizing antibodies against HIV. Pending review by the U.S. Food and Drugs Administration, the microparticle based oral vaccine against HIV-1 will be assessed in clinical trials in seronegative human volunteers.

Human antibody responses to outer envelope antigens of Porphyromonas gingivalis serotypes

Immunological studies examining the homogeneity of the major antigenic components of P. gingivalis have suggested 3 serotypes and have indicated a limited distribution of the serotypes in an individual patient. These studies prompted us to define the immunodominant antigens and distribution of immune responses to P. gingivalis serotypes. Serum IgG antibody levels in periodontitis patients in the present study were most frequently elevated above the normal subjects when tested against P. gingivalis serotype A (i.e., 33277). Nearly 1/3 of the patients showed significantly elevated antibody to multiple serotypes of the P. gingivalis apparently resulting from cross-reacting antigens. We determined distinctive differences among outer envelope protein and antigen patterns obtained from the three serotypes. Moreover, the results identified considerable similarities in the qualitative and quantitative antigen response patterns among patients to a particular serotype. There was a strong positive correlation between IgG antibody levels (ELISA) and the total level of reactivity determined in the immunoblots, as well as a positive correlation to the proportion of antibody to particular antigens. These findings suggest that responses to these antigens comprised a major portion of the response to the intact microorganism. Additionally, the detection of antibody to particular antigen bands was indicative of early responses to each of the P. gingivalis serotypes. The results of our study indicate that a subpopulation of periodontitis patients develop an extensive serum antibody response often to multiple serotypes of P. gingivalis and may define a patient population with a P. gingivalis disease. Finally, our results indicate a more consistent antigenic composition for P. gingivalis which may enhance the potential for strategies to immunologically interfere with disease caused by this microorganism.

Infection determinants at extremes of age

The immune defence of the full-term neonate is compromised in several ways. Although adequate numbers of B lymphocytes are present, antibody production may be delayed compared with the adult. Decreased levels of complement components contribute to the impaired opsonization potential of newborn sera and in turn, to impaired chemotactic responses of neonatal polymorphonuclear leucocytes (PMN). Multiple abnormalities in neonatal PMN function, coupled with deficient bone marrow supplies during stress, contribute greatly to the increased vulnerability to infection of neonates. Infection is a major problem for infants born before 28 weeks. Their serum IgG antibody levels are extremely low and the deficiencies in complement levels and PMN chemotatic responses noted in full-term neonates are even more marked and persist for longer. Opsonic activity decreases with decreasing gestational age and septicaemic pre-term infants are liable to develop neutrophil storage pool exhaustion. In contrast to neonates, the effect of ageing on the immune response is more variable but the changes in cell-mediated immunity have the greatest clinical impact. This decline in T cell function alters the balance between the immune system and intracellular organisms and leads to reactivation of previously controlled infections. Impaired function of immunoregulatory cells contributes to the poor and unsustained antibody responses of the elderly to primary and booster immunizations. Immunosenescence contributes to the morbidity and mortality of old age by several mechanisms, but mainly through an increased susceptibility to infection.

326 IGG SUBCLASSES AND ANTIBODIES TO STREPTOCOCCUS PNEUMONIAE IN IMMUNODEFICIENT CHILDREN WITH CHRONIC LUNG SUPPURATIONS

We studied 17 immunodeficient children 4-14 years old (9 with hypogammaglobulinemia, 8 with selective IgA deficiency) all having chronic lung suppurations. The highest rate of S.pneumoniae colonization was in children with IgA deficiency (up to 50%) with noncapsular H.influenzae found in 43%. Antibody levels to S.pneumoniae capsular polysaccharides, C-polysaccharide, protein antigens were studied in serum, saliva and bronchoalveolar lavage fluid by ELISA; IgG subclasses in serum - by radial immunodiffusion. All patients had absent or very low levels of pneumococcal IgA-antibody in secretions. In spite of the presence of serum IgG-antibody (even their high levels in selective IgA deficiency) all children had severe suppurations indicating the major role of local immune response in bacterial clearance from the respiratory tract. It also suggests that serum IgG antibodies do not pass in sufficient quantity into bronchial secretion due to a peribronchial fibrosis. Low serum IgG-antibody levels were found in children with hypogammaglobulinemia, however two patients with combined IgA - IgG subclass deficiency (IgA plus IgG1, IgG3, IgG4 and IgA plus IgG4) had almost normal serum antibody level probably due to the relation of pneumococcal antibody to IgG2. Clinical data indicate that different rate of hypogammaglobulinemia expression may explain the diversity in manifestations of primary humoral immunodeficiency.

Surface and excretory/secretory antigens of fourth-stage larvae and adult Ostertagia circumcincta

With the use of an enzyme-linked immunosorbent assay (ELISA), it was revealed that surface antigens of both adult and fourth-stage larvae (L 4) of Ostertagia circumcincta induced high levels of serum IgG antibodies, while serum IgA antibody levels were low but increased significantly ( P <0.01) after infection. Immunofluorescence studies on the surface of viable L 4 and adult nematodes showed that the IgG response was stage-specific only in animals vaccinated with adult surface extracts. The results of Western blot analysis using these antibodies suggested that at least eight polypeptides were shed from the L 4 surface to the environment and that infection induced (or boosted) IgG antibody against a further four polypeptides. A comparison of reactivity of pre- and post-infection sera of sheep vaccinated with adult nematode surface antigens suggested that only one of the antigens stripped from the nematode surface was immunogenic and/or present in a concentration sufficient to induce an IgG response following parenteral vaccination. Infection boosted the IgG antibodies to a further four polypeptides. Only one polypeptide of 63 kDa seems to be shed in vivo from the adult nematode surface. Ten to eleven antigens were recognised in adult excretory/secretory products by serum IgG of multiple-infected sheep.

Infection by Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans, and antibody responses at different ages in humans.

This study examined the serum IgG and IgM responses against Porphyromonas gingivalis and 3 serotypes of Actinobacillus actinomycetemcomitans, and the correlations of these responses with age and homologous infection. A total of 90 individuals were included in this study: 40 subjects with gingivitis, 40 periodontally healthy subjects, and 10 adult periodontitis subjects. The subjects in the gingivitis and periodontally healthy groups were divided into 4 stages based on their physiological age: early childhood, school age, puberty, and adult. In the gingivitis group, there was a positive correlation between increase in age and increase in serum IgG antibody levels against P. gingivalis until puberty. However, no statistically significant difference was found between the puberty stage and the adult stage. The average level of IgG antibodies against A. actinomycetemcomitans in the school age gingivitis group was significantly higher than that in the early childhood gingivitis group for all serotypes (p < 0.01). In serotype c, IgG antibody levels in the school age gingivitis group were significantly higher than in the early childhood gingivitis group or the adult gingivitis group (p < 0.01). With both P. gingivalis and A. actinomycetemcomitans, positive correlations between elevated IgG level and infections by these microorganisms were found in the puberty gingivitis and adult periodontitis groups.

Serum antibody opsonic activity against Actinobacillus actinomycetemcomitans in human periodontal diseases.

Actinobacillus actinomycetemcomitans is frequently associated with severe periodontitis. Many periodontitis patients have elevated levels of serum IgG antibodies to A. actinomycetemcomitans, but the role of these antibodies is unknown. This study evaluated the functional capacity of anti-A. actinomycetemcomitans IgG antibody to enhance phagocytosis of A. actinomycetemcomitans by polymorphonuclear leukocytes. Chemoluminescence assays were done using sera from 64 subjects, 61 of whom had severe periodontitis; results were compared with the subject's anti-A. actinomycetemcomitans IgG titer and avidity. There was a strong correlation between chemoluminescence and antibody log titer (P < .00001) and a weak correlation between chemoluminescence and antibody avidity (P < .05). The results support the hypothesis that anti-A. actinomycetemcomitans IgG antibodies are important in promoting phagocytosis and killing of A. actinomycetemcomitans. Subjects who develop high levels of highly avid antibodies against A. actinomycetemcomitans may have greater resistance to continued or repeated infection by this pathogen.

Newcastle disease virus: virus replication in the Harderian gland stimulates lacrimal IgA; the yolk sac provides early lacrimal IgG

An indirect immunoperoxidase monolayer assay was used to measure the location of virus and class-specific antibodies to Newcastle disease virus (NDV) of chickens. The intra-ocular vaccination of chicks with the Ulster and Hitchner B1 strains of NDV resulted in the highest titre of virus being recovered from the Harderian gland (HG) at 10 6 iu 0.1 g tissue without any accompanying virus in the faeces. Maternal IgG antibody which was detected in the lacrimal fluid at 1 50 of serum levels of IgG antibody could prevent this replication. Lacrimal IgA antibody to NDV was shown to be absolutely dependent on local virus replication for its production because it reached titres of 10 3 after local intra-ocular infection compared with <10 1.5 after two intravenous inoculations of inactivated virus. Biliary IgA, by contrast, reached 10 3.5 after either immunisation schedule. Lacrimal IgG and IgM antibody to NDV occurred at 1–9% of the titres of serum antibody to NDV after immunisation with inactivated virus or the passive transfer of NDV-immune serum between chickens. This percentage increased to 13–33% of serum titres after intra-ocular infection with NDV as if the local replication of NDV in the HG stimulated lacrimal antibody of all classes. This is the first report of NDV replication in the HG and of virus-specific IgM in the lacrimal fluid.

Biodegradable microparticles for oral immunization

Ovalbumin (OVA) was entrapped in poly(lactide-co-glycolide) microparticles and administered to mice. Following intraperitoneal immunization, the microparticles induced both proliferative T-cell responses and cytotoxic T-cell responses in spleen cells. Following oral immunization, the mean salivary IgA antibody response to microparticles was significantly greater than the response to soluble OVA (p < 0.0001). Serum IgG antibody levels were also significantly greater in the group administered microparticles (p < 0.001). Cholera toxin B subunit was also entrapped in microparticles. Following oral immunization in mice, specific antibody-secreting cells were detected both in the spleens and in the mesenteric lymph nodes.

Localization of inhaled trimellitic anhydride to lung with a respiratory lymph node antibody secreting cell response

Male Sprague-Dawley rats were exposed to trimellitic anhydride (TMA) by inhalation (500 μg/m 3), 4 hours a day, for 1 to 10 days. TMA was localized to lung cells by immunoelectron microscopy. Enzyme-linked immunosorbent assay (ELISA) and Western blot analysis were used in an attempt to localize TMA to lung lavage proteins. The lung-associated lymph node (LALN) B-lymphocyte response was measured by quantitation of immunoglobulin (Ig)G, IgA, and IgM antibody secreting cells specific for TMA rat serum albumin (TMRSA) by use of the enzyme-linked immunospot assay (ELISPOT) method. The IgG, IgM, and IgA antibody response to TMRSA in serum and lavage fluid was quantitated by ELISA. Lung injury was assessed by the number of external lung hemorrhagic foci and lung weight. Immunoelectron microscopy localized TMA to alveolar and bronchial cells on all exposure days. ELISA detected trace amounts of TMA haptenized lavage proteins that could not be detected by Western blot analysis. A marked increase occurred in lung injury from day 7 to 10. The LALN IgG, IgA, and IgM antibody secreting cell response to TMRSA paralleled measures of lung injury. IgG, IgM, and IgA serum and lavage antibody to TMRSA were correlated with lung injury measures. Lavage and serum IgG antibody levels had the highest correlation with lung injury.

IgG antibodies to Loxosceles sp. spider venom in human envenoming

The presence and specificity of IgG antibodies produced by patients with loxoscelism were studied. The loxoscelism diagnosis was supported mainly by clinical parameters. A search for IgG antibodies anti- Loxosceles gaucho venom in patients with loxoscelism submitted to serumtherapy showed antibodies in four out of 20 patients. The IgG antibodies were detected as early as 9 days and as late as 120 days after bite. The highest IgG antibody titer was 1:640 and the lowest was 1:80. Immunoblotting tests showed that human anti- L. gaucho IgG antibodies recognize preferentially the components responsible for the dermonecrotic and lethal activities of the venom. A comparison of the clinical picture, the level of serum IgG antibodies and the dose of antivenom administered suggest that there is no relationship between these parameters.

Cats with single Brugia pahangi infections: relationship between parasitological status and humoral responses to somatic and surface parasite antigens.

Cats given a single inoculation of Brugia pahangi infective larvae (L3) were retrospectively allocated into three groups according to parasitological outcome of infection. Recognition of somatic and surface antigens of B. pahangi by sera from each group was compared by ELISA, immunoelectroblotting, and immunoprecipitation techniques. In cats that never became microfilaraemic mean serum IgG antibody levels against somatic extracts from adult male worms, L3, and microfilariae (mf) were higher than levels in cats that initially became microfilaraemic (mf + ve) then spontaneously became nonmicrofilaraemic (mf - ve). The lowest levels of antibody against each stage were found in cats that remained persistently mf + ve. Antigenic components of 18 kD and 22 kD in somatic extracts of adult worms and L3 were recognized by sera from cats that never became mf + ve and by spontaneously mf - ve cats, but not by sera of persistently mf + ve cats. When radioiodinated surface antigens of mixed adult worms and microfilariae were immunoprecipitated by sera from cats in the three groups, no correlation was observed between recognition of individual antigen components and parasitological outcome of infection.

Antibodies to native type III collagen in the serum of patients with Kawasaki disease.

Pathological studies have revealed that the vasculitis in Kawasaki disease (KD) begins in the intima and the adventitia of blood vessels resulting in panvasculitis. In the present study we investigated the possibility that auto-antibodies to types III and II collagen are involved in the vascular injury. Seven out of 38 patients (18%) with KD had elevated serum levels of IgG antibody to type III collagen. None had increased serum antibodies to type II collagen. Specificity of the antibody to type III collagen in patients with KD was 86%. Three out of seven KD patients (42.9%) with coronary complications had elevated serum levels of the antibody. It is conceivable that the more severe the inflammation of systemic blood vessels, the more frequently antibodies to type III collagen are detected and coronary complications develop. Accordingly, this antibody may be secondarily detected in the serum of KD when systemic blood vessels are severely damaged. Detection of antibodies to type III collagen might be a risk factor predicting coronary complications.