Serum IgG Values Research Articles

Field trial to evaluate immunogenicity of a glycoprotein I (gE)-deleted pseudorabies virus vaccine after its administration in the presence of maternal antibodies

SUMMARY A field trial was conducted on a commercial swine farm quarantined because of infection with pseudorabies virus. The purpose was to investigate, in growing pigs born to hyperimmunized sows, the immunogenicity of a vaccine with a glycoprotein I (gE) deletion. One hundred twenty pigs were assigned at random to 1 of 3 vaccination schedules at ages: 8 and 12 weeks; 8, 12, and 14 weeks; and 8,12, and 16 weeks. Immune response was measured at 8, 12, 14, 16, and 18 weeks, using the serum neutralization test, a screening elisa, and assays of IgG and IgA in serum and nasal secretions. Results of the serum neutralization test and the screening elisa indicated that, for pigs vaccinated only at 8 and 12 weeks, the percentage of pigs with pseudorabies virus serum antibodies decreased substantially by 18 weeks; for pigs given a booster at 14 or 16 weeks, the prevalence of serum antibodies at 18 weeks was higher, with 16-week booster vaccination eliciting the best response. At each age, nasal IgA and IgG values were highly correlated (r ≥ 0.70), as were serum IgA and IgG values; correlations of serum with nasal IgA and IgG values were somewhat lower (approx range, r = 0.40 to 0.70). Nevertheless, an increase in serum IgA or IgG values on vaccination was no guarantee of an increase in nasal IgA or IgG values. For serum and nasal mucosal antibodies, a poor immune response was associated with high quantities of maternally derived antibodies. Vaccination at 16 weeks was necessary to ensure eliciting of an immune response in almost all pigs.

Intravenous immune globulin prophylaxis of late-onset sepsis in premature neonates

To determine whether a single dose of intravenously administered immune globulin (IVIG) decreases late-onset sepsis in premature infants, we prospectively entered 753 neonates with birth weight 500 to 2000 gm, gestation ≤34 weeks, and age ≤12 hours into a multicenter, double-blind, controlled trial. Infants were randomly selected to receive a single intravenous infusion, 10 ml/kg, of either IVIG (500 mg/kg) or albumin (5 mg/kg) and were observed for 8 weeks for infection. Maternal and neonatal risk factors for infection did not differ between groups. Although serum IgG values before infusion were related to gestation ( R = 0.62), the change in serum IgG or half-life of IgG after IVIG infusion was not ( R ≤ 0.09). The serum IgG concentration was increased ( p <0.05) in IVIG-treated patients for 8 weeks. There were 88 episodes of late-onset sepsis in 79 neonates (10.5%). Causative organisms included the following: Staphylococcus epidermidis (37 episodes), Enterococcus (9), Staphylococcus aureus (7), Candida (6), Escherichia coli (6), and multiple organisms (11). Sepsis, death, and death as a result of infection were unaffected by treatment. We conclude that a single infusion of IVIG, 500 mg/kg, shortly after birth was not effective prophylaxis for late-onset infection in premature neonates. Future studies of late-onset sepsis prophylaxis should consider IVIG with known pathogen-specific antibody concentrations against organisms causing these infections, in particular S. epidermidis. (J P EDIATR 1994;125:922-30)

Antibody response and antibody affinity maturation in cats with experimental proliferative immune complex glomerulonephritis

An experimental model of proliferative glomerulonephritis (GN) in the cat, which closely resembles human proliferative forms of GN, has been used to study the role of antibody and antibody affinity in the development of immune complex-mediated renal disease. The serum IgG and IgM antibody response to antigen, average antibody affinity (avidity) and affinity heterogeneity of the IgG and IgM populations was assessed at varying times after commencement of chronic immunization with the antigen, human serum albumin (HSA), by enzyme immunoassay. Cats could be classified according to whether they were “low”, “intermediate” or “high” IgG responders, by quantification of serum IgG values. Cats with the lowest serum IgG values failed to develop glomerulonephritis. However, there was no relationship between actual IgG values and the severity of the induced disease. In contrast to IgG, there was no division of cats into low or high IgM anti-HSA responders. Again, cats with the lowest IgM values failed to develop GN, but, more interestingly, a late, marked increase in serum IgM anti-HSA occurred only in cats that developed clinical signs of GN (anterior uveitis and nephrotic syndrome). Maturation of average, functional IgG affinity (avidity) for HSA following chronic immunization was clearly demonstrated for all cats. At the end of the experiment, all cats had IgG of high affinity for HSA and the average affinity heterogeneity of the IgG populations was less than in measurements taken earlier. Values of IgG affinity at the end of the experiment were very similar both in cats which developed GN and in those which remained clinically, biochemically and pathologically normal. In contrast to IgG antibody, some cats developed IgM of increased affinity, whilst others produced antibody of reduced affinity, following chronic immunization. There was no correlation between the development of disease and the production of either low or high affinity IgM antibody. Data indicated that an alteration in IgM affinity occurred at a late stage, as serum IgM levels increased, in cats which progressed to develop GN. These findings suggested that an increase in both serum IgG and IgM anti-HSA values, in particular IgM, was associated with the development of a more severe immune complex renal disease in these cats. Although there was no evidence that differences in the average affinity of either the IgG or IgM antibody populations for HSA, were associated with the development of disease, the increase in IgM values was also accompanied by a concomitant alteration in IgM affinity for antigen. Such alteration in IgM preceded the development of proteinuria and clinical signs of GN by 4 to 5 weeks and appeared to be indicative for the development of proliferative GN in this feline model of GN.

Randomized trial of granulocyte transfusions versus intravenous immune globulin therapy for neonatal neutropenia and sepsis

We prospectively studied newborn infants with sepsis and neutropenia who were randomly selected to receive standard supportive care and either adjuvant granulocyte transfusions or intravenous immune globulin (IVIG) infusions; 21 infants received granulocyte transfusions and 14 received IVIG infusions. Half of the patients were premature (gestational age less than or equal to 32 weeks); the average postnatal age was 5 days (range 3 to 8 days). All infants had neutropenia by the criteria of Manroe et al., and the mean average bone marrow neutrophil storage pool ranged between 35% and 37%. There were no significant differences with respect to serum IgG, IgA, IgM, and total hemolytic complement values between treatment groups or between survivors and nonsurvivors. Clinical severity as defined by hypoxia, acidosis, and hypotension was similar between treatment groups. Group B streptococcus was the most common organism identified and accounted for almost 33% of all bacterial isolates. There was a significantly different survival rate in the group receiving polymorphonuclear leukocyte transfusions (100%, 21/21) compared with the group receiving IVIG infusions (64%, 9/14; p = less than 0.03). There were no significant complications in either treatment group with respect to fluid overload, secondary infection, blood group sensitization, pulmonary complications, or graft-versus-host disease. This pilot study suggests a possible benefit of granulocyte transfusions compared with 'IVIG therapy in the adjuvant treatment of neonatal neutropenia and overwhelming bacterial sepsis.

Serum and CSF immunological findings in ALS

Serum and CSF immunological findings were analysed in 37 patients with amyotrophic lateral sclerosis (ALS). ALS patients had significantly higher mean values of serum IgG and complement component C4 and significantly lower mean value of total haemolytic titre of complement (THC) compared with normal controls. Incidence of immune complexes (ICs) was significantly higher in sera of ALS patients than in normal controls. There was no significant difference regarding mean serum levels of IgM, IgA, and complement components C3 and Factor B between patients and controls. The blood-brain barrier (BBB) damage was found in 46% of patients. Intrathecal IgG synthesis was detected in six patients (16%). These results support the hypothesis of immune system involvement in ALS.

Changes in serum proteins (albumin, immunoglobulins and acute phase proteins) in pulmonary tuberculosis during therapy

Serum levels of three immunoglobulins (IgG, IgA & IgM), albumin and six acute phase proteins (α1-antitrypsin, haptoglobin, transferrin, α2-macroglobulin, complements C3 & C4) were measured by immunoelectrophoresis in 57 patients with pulmonary tuberculosis when they were first diagnosed, and followed at 1 month, 2 month and 4 month intervals during anti-tuberculosis treatment. These values were compared to those from 41 healthy controls. Significant increases were observed in the initial values of serum IgG, IgM, α1-antitrypsin and haptoglobin, while transferrin and α2-macroglobulin levels were significantly reduced. No changes were observed in the levels of serum albumin, IgA and complement C3. Levels of all measured proteins decreased with treatment. However, at 4 months, IgG and α1-antitrypsin were still significantly elevated when compared to control values, while the level of haptoglobin had decreased to a level significantly lower than that of the control value.

Photoradiation Therapy of Animal Tumors and Nasopharyngeal Carcinoma

Both animal tumors and human nasopharyngeal carcinoma were submitted to a photoradiation therapy (PRT) trial in order to determine the efficacy and side effects of PRT, as well as to elucidate its mechanism of cytotoxicity. In animal tumors, the inhibition rate was 70%, and of 20 patients, eight achieved complete remission, and ten, significant remission, with an overall response rate of 90%. The blood picture and the values of serum IgG, IgM, IgA, and C3 all remained stable post-PRT. Only three patients developed mild generalized skin photosensitive reactions, and these did not affect subsequent treatment. There was no immunosuppressive effect as evidenced by a tritium-labeled thymidine-incorporated lymphocytoblast transformation assay performed both before and after PRT. Ultrastructural studies at different time intervals after PRT highly suggested that the mitochondria and rough endoplasmic reticulum were among the first organelles to be damaged.

Salivary immunoglobulin concentrations in predentate and edentulous mouths

The concentrations of IgA, IgG and IgM in whole saliva of predentate babies, dentate adults, and edentulous old people, and the salivary IgG concentration of dentate old people, were determined using a solid phase radioimmunoassay. A highly significant difference in IgG concentrations was found between toothless and dentate people. The average IgG concentration in the saliva of edentulous old people was 5.2 mg/1, which was about 20% of that of dentate old people. The salivary IgG content of babies was only 1.7 mg/1, which was in concordance with the low postnatal serum IgG values. The salivary IgA level in this age group was also low. The edentulous old people tended to have decreased IgM values, and the predentate babies tended to have increased IgM values compared with the dentate adults.

Serum IgG levels in full term preterm and SFD neonates.

Cord blood IgG levels were estimated in fifty normal full term, preterm and small for date babies. The values were significantly lower (p<0·05) both in preterm and SFD babies when compared with normal full term (AGA) newborn. A direct correlation was found to exist between IgG concentration and gestation age in pretern as well as full term (ABA). Small for date babies showed significantly lower (p<0·05) IgG levels as compared to preterm (AGA) neonates suggesting the effect of inadequate placental function as a contributing factor in decreased serum IgG values in small for date babies.

INTRAVENOUS GAMMAGLOBULIN THERAPY IN IMMUNODEFICIENT CHILDREN

We have treated 23 children aged 6-15 years affected with agammaglo bulinemia or severe hypogammaglobulinemia with IgG serum levels lower than 100 mg% with IV gammaglobulin (Sandoglobin) at the dose of 150-300 mg/kg/3 weeks for two years. The children suffered from severe and recurrent bacterial infections, mainly of the respiratory tract, leading to chronic tissue damage. The had been previously treated with IM gammaglobulins (0,8 ml/kg/3 weeks), but their serum IgG values were never higher than 75 mg%. The results are summarized in the following Table, in which we have compared the data of the follow-up after two years of treatment with IV gammaglobulin and of the follow-up after a one-year course of IM gammaglobulins.Minor adverse reactions (chills, fever, abdominal pain) were observed only in some children and in the first months of therapy. These data demonstrate that IV administered serum immune globulin therapy dramatically reduced infectious diseases in children with immunodeficiencies.

IgG subclasses in nonallergic children with chronic chest symptoms

Immunoglobulin and IgG subclass measurements were made on sera from 37 children thought to have asthma whose chronic chest symptoms were unexplained by allergy. There was a higher proportion of low or low-normal levels of IgG subclasses 1, 2, and 4 in these children than in normal children. Those who had low serum IgG values on initial measurement had a higher proportion of low or low-normal levels of IgG1, IgG2, and IgG4; those who had normal IgG values had a higher proportion of low or low-normal levels of IgG2 and IgG4. Thus a normal serum concentration of IgG did not exclude the possibility of an abnormal level of IgG2 or IgG4. Our experience suggests that abnormal levels of IgG subclasses might play an etiologic role in the chronic chest symptoms in some of these children.

Progression of cystic fibrosis lung disease as a function of serum immunoglobulin G levels: A 5-year longitudinal study

Seventy children with cystic fibrosis were studied over a 5-year period to assess the relationship between serum immunoglobulin G levels and progression of cystic fibrosis lung disease. Patients were grouped according to their serum IgG values (low, normal, or high) and evaluated with serial pulmonary function testing, radiographic and immunologic studies, and clinical observation. The children with persistent hypogammaglobulinemia G showed significantly better lung function, better weight for age, fewer hospitalizations for pulmonary exacerbations, less colonization with Pseudomonas aeruginosa, and slower decline in pulmonary functions than did age-matched patients with normal or high IgG levels. Death occurred in five of eight (63%) patients with hypergammaglobulinemia, three of 30 (10%) with normogammaglobulinemia, and one of 32 (3%) with hypogammaglobulinemia. No deaths occurred in the 15 patients with persistent hypogammaglobulinemia. These data indicate that children with cystic fibrosis and hypogammaglobulinemia G have milder lung disease and slower deterioration in pulmonary function than do age-matched patients with normal or elevated immunoglobulin G values. The mechanisms accounting for this finding are unclear.

Vaccine for enterotoxigenic Escherichia coli based on synthetic heat-stable toxin crossed-linked to the B subunit of heat-labile toxin.

Synthetically produced Escherichia coli heat-stable toxin (ST) was conjugated to the nontoxic B subunit of the heat-labile toxin (LT) by the carbodiimide reaction. Modifying the molar ratio of toxins mixed and the ratio of carbodiimide added to the toxins permitted synthesis of conjugates with any desired degree of proportional antigenicity for each toxin component. Immunization of rats by the parenteral/peroral routes with cross-linked vaccine containing 39% ST and 61% B subunit antigenicity, with 0.06% residual ST toxicity, evoked fourfold to sevenfold increases over control values of serum IgG and mucosal secretory IgA antitoxin titers to each of the component toxins, thus providing significant (P less than 0.001) protection against challenge with either LT or ST or with viable heterologous strains which produce these toxins. These observations show that cross-linking synthetic ST to the B subunit results in a nontoxic vaccine that provides protection against all types of enterotoxigenic E. coli.

Secretory IgA: immune defence pattern in ankylosing spondylitis and klebsiella.

Saliva secretory IgA (sIgA), secretory component (SC); serum immunoglobulins (IgG, IgA, IgM), complement (C3, C4), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) were performed in 32 patients with ankylosing spondylitis and 29 normal controls. They were investigated for carriage in the faeces of Klebsiella spp. on 3 occasions over the previous months. Throat swabs and urine were cultured at the same time as immunological estimations were done. 24-hour urine sIgA specimens were studied in 13 patients and 12 normal controls. Significantly raised mean values of saliva sIgA and serum IgG, IgA, C3, and C4 were found in patients with raised values of serum ESR and CRP levels when correlated with controls. Raised values of sIgA in saliva, which is an important factor of the local immune defence mechanism of mucosal surfaces, suggests the presence of an antigenic stimulus from the gastrointestinal system in ankylosing spondylitis during activity of disease.

Serological profiles in Indian post kala-azar dermal leishmaniasis

The sera of 20 Indian post kala-azar dermal leishmaniasis (PKADL) patients were analysed for immunoglobulin (IgG, IgM and IgA), third component of complement (C3) and specific antibody contents and the results compared with those of normal controls and kala-azar (KA) patients as obtained in an earlier study. Mean values of serum IgG and IgM in PKADL were found to be significantly higher than those of normal controls, although these values were substantially lower to those of KA patients. No significant difference, however, was noted in the mean levels of serum IgA and C3 between PKADL and control groups. Specific antibodies to Leishmania antigen could be demonstrated in PKADL sera by the indirect haemagglutination (IHA) and enzyme-linked immunosorbent assay (ELISA) methods. Most of these antibodies belonged to IgG class although some IgM antibodies were also demonstrable. Antibody titre ranges in PKADL sera were, however, definitely lower than those of KA sera. A reasonably good correlation between the severity of dermal lesions and IgG-ELISA titres was obtained. Of 12 chronic PKADL cases, only four and ten were found to be serologically positive by IHA and micro-ELISA methods respectively. All eight fresh cases were seropositive by both these tests. Analysis of the data suggests an over-all difference between the serological profiles of PKADL and KA patients.

An epidemiological survey of immunological abnormalities in asbestos workers: II. Serum immunoglobulin levels

A significant elevation of serum IgA and IgG was found in female asbestos workers below age 36. Higher values of serum IgA, IgG, and IgM were found in male asbestos workers over age 35, when compared to matched controls. Female asbestos workers, over age 35, statistically differ from their controls only with respect to IgG levels. Patients, with asbestosis and with an impairment of blood oxygen saturation, contribute greatly to the elevation of serum immunoglobulin levels in asbestos workers. The asbestosis process, but not chronic bronchitis, is responsible for high serum IgA and IgG levels.

Fractionation of Antibodies to L-Cell Colony Stimulating Factor by Affinity Chromatography

Purified L-cell colony-stimulating factor (CSF) was coupled to cyanogen-bromide-activated Sepharose and used to selectively fractionate antibodies to this factor. With the use of a simplified two-step washing and elution technique, there was 50%--70% binding of the anti-CSF, with recovery of 60%--100% of the bound material. Both the native antiserum and purified anti-CSF fractions were inhibitory to murine granulocyte-macrophage colony formation. The purified antibodies contained only IgG and were reduced in protein concentration to 0.1% of the serum IgG values. These fractions should prove useful tools for the study of granulocyte and macrophage differentiation.

Fractionation of antibodies to L-cell colony-stimulating factor by affinity chromatography

Purified L-cell colony-stimulating factor (CSF) was coupled to cyanogen- bromide-activated Sepharose and used to selectively fractionate antibodies to this factor. With the use of a simplified two-step washing and elution technique, there was 50%--70% binding of the anti- CSF, with recovery of 60%--100% of the bound material. Both the native antiserum and purified anti-CSF fractions were inhibitory to murine granulocyte-macrophage colony formation. The purified antibodies contained only IgG and were reduced in protein concentration to 0.1% of the serum IgG values. These fractions should prove useful tools for the study of granulocyte and macrophage differentiation.

Cytostatic Treatment of Glomerular Diseases

Fifty patients with renal glomerular diseases entered a double-blind cross-over study on the effect of cyclophosphamide; 38 had received neither corticosteroids nor cytostatic drugs before joining the study. Cyclophosphamide was given for 4 months in doses decreasing from 3 to 1.5 mg/kg b.wt. Cyclophosphamide caused a 46% decrease in the 24-hour excretion of urinary protein and a decrease in serum creatinine within the normal range. Albumin, transferrin and IgA in urine, as well as albumin clearance and the sieving coefficient of albumin, changed parallel to the total urinary protein. The initial values of proteinuria and serum complement were of prognostic significance for the effect of cyclophosphamide in serum creatinine. We were unable to demonstrate a prognostic significance for the variables: clinical diagnosis, renal histology, arterial BP, initial values of serum creatinine and IgG, IgA and IgM in serum and urine. ESR appeared to be the most reliable acute phase reactant. No differences were found between the changes in renal histology during cyclophosphamide or placebo.

Air Pollution and Respiratory Infection

Increased incidence of respiratory infections has been mentioned in air polluted area. The incidence rates of pharygolaryngitis and common cold + bronchitis have been increased and are much higher in the air polluted area in Yokkaichi than control nonpolluted area. However, the level of SO2 in this area has decreased and averaged 0.03 ppm in 1972 compared with 0.08 ppm in 1964. The prevalence rates of rhinitis and tonsillitis of school children was significantly higher in this area in 1972.A distinct increase in DNA labeling index of the epithelial cells of the trachea was observed at the first week of exposure period to SO2 in mice. The labeling index returned to preexposure level after the second week of the exposure. In a period from the third week to 15th, the tracheal epithelium was replaced by tall ciliated columnar one which contained a large number of PAS positive cells. The mice exposed to SO2 for 4 weeks were inoculated influenza virus PR8 intranasally. The inflammatory changes in the nasal cavity in the SO2 + virus group were severer and spread much rapidly than virus control. In addition, HI titer developed much rapidly and reached higher level than virus control.The mean concentration of parotid salivary IgA of the normal school children in the polluted area was not significantly different than that of nonpolluted area. But the variance was significantly different.Individual value of serum IgG of the mice exposed to NO2 from intrauterine to the 4th week pcstpartum varied considerably compared with consistent value of control.The incresed severity of virus infection in SO2 mice appeared to result from interaction between effects of SO2 and infection. This interaction could increase the severity of infection. Although the manner of this interaction still needs to be answered, it should be considered that air pollutants may affect the immune response.