Detection of serum antibodies against Chlamydia pneumoniae by ELISA

Chlamydia pneumoniae causes pneumonia and other respiratory infections in children, adolescents and adults. We tried to evaluate the diagnostic value of detection of serum antibodies by ELISA for C. pneumoniae infections in Japanese children. Serum IgG, IgA and IgM antibodies to C. pneumoniae were determined by the microimmunofluorescence (MIF) test. Serum IgG and IgA antibodies were also determined by ELISA test kits. Results obtained by ELISA were compared with those obtained by MIF test. IgG antibody to C. pneumoniae was detected in 135 (39.5%) by ELISA and in 125 (36.5%) by MIF out of 342 sera from Japanese infants and children without respiratory infections (aged from 2 months old to 15 years old). IgA antibody to C. pneumoniae was detected in 129 (37.7%) by ELISA and in 117 (34.2%) by MIF out of 342 sera tested. Of 342 specimens 113 were IgG-positive by ELISA and MIF (sensitivity: 90.4%, specificity: 89.9%, r = 0.853). Of 342 sera 28 had IgG antibody titers of 1:256 and none had titers 1:512 or higher by MIF. Of 28 infants and children a total of nine were less than 4 years of age. On the other hand, of 342 specimens 99 were IgA-positive by ELISA and MIF (sensitivity: 84.6%, specificity: 86.7%, r = 0.769). Of 342 sera 16 had IgA antibody titers of 1:256 or higher by MIF. Of 16 infants and children, ten were less than 4 years of age. ELISA had excellent sensitivity and specificity relative to MIF test for detection of IgC and IgA antibodies to C. pneumoniae. It was suggested that C. pneumoniae infection in Japanese infants and children under 4 years of age was not infrequent.     

Low immunoglobulin G3 levels in wheezy children

This study aimed to investigate the prevalence of IgG subclass deficiency in wheezy children aged <3 y. Serum levels of IgA, IgE and IgG subclasses were measured in 310 children with recurrent wheezing and in 100 healthy controls. IgG3 levels were below the normal lower limit in 123 (39.6%) patients. This finding may reflect delayed maturation of the immune system, predisposing young children <3 y of age to wheezing.     

Atrophy of the corpus callosum associated with cognitive impairment and widespread cortical hypometabolism in carotid artery occlusive disease

BACKGROUND: The independent influences of small-intestinal bacterial overgrowth and old age on mucosal immunoglobulin production and secretion have not been assessed. This is an important issue, since luminal IgA deficiency may exacerbate small-intestinal bacterial overgrowth, the prevalence of which is high in selected elderly populations. METHODS: Proximal small-intestinal aspirates were obtained from 33 subjects for bacteriologic analysis and measurement of total IgA, IgM, total IgG. IgG subclass, and IgD concentrations. IgA subclasses were measured in 24 unselected subjects. Serum immunoglobulin and salivary IgA concentrations were measured in all subjects. RESULTS: IgA2 and IgG3 were predominant IgA and IgG subclasses in proximal small-intestinal luminal secretions. Luminal concentrations of IgA2 and IgM, but not IgG3 or any other IgG subclass, were significantly increased in small-intestinal bacterial overgrowth, which was present in 19 of 33 (57.6%) subjects. Old age did not influence these levels. Luminal immunoglobulin concentrations did not correlate significantly with either serum or salivary values. IgD was not measureable in proximal small-intestinal secretions. CONCLUSIONS: Increased luminal concentrations of the secretory immunoglobulins, IgA2 and IgM, occur in small-intestinal bacterial overgrowth. Local investigation is mandatory when assessing the mucosal immunopathology of this disorder. Luminal IgG3 is unlikely to be predominantly derived from serum. Old age does not independently influence luminal immunity.     

Infant respiratory function after RSV-proven bronchiolitis

The mechanisms underlying the increased risk of wheezing in early childhood following acute bronchiolitis in infancy remain unclear. Previous studies have reported significant abnormalities in infant respiratory function after clinical recovery from bronchiolitis, but are difficult to interpret because of the frequent omission of a concurrent comparison group. Respiratory function was compared within pairs of previously healthy full-term caucasian infants admitted with a first episode of acute bronchiolitis to an inner London hospital, and age- and sex-matched control infants without prior wheezing, asthma, or lower respiratory illness who were recruited from local general practices. Respiratory function was measured in 29 control and 29 asymptomatic index infants, with measurements in the latter done at a median interval of 36 wk (range: 16 to 49 wk) after admission, when 16 (55%) had experienced subsequent wheezing. Index infants tended to be autumn-born and of shorter gestation than control infants, to have younger mothers, and to have been exposed to tobacco smoke. There were no statistically significant differences in plethysmographic FRC, initial inspiratory airway resistance (Raw), or respiratory system compliance (mean [index minus control] within-pair difference [95% confidence interval]: -11 ml [-29, 7 ml]; -0.2 kPa/L/s [-0.7, 0.4 kPa/L/s]; -8 ml/kPa [-21, 4 ml/kPa], respectively), but respiratory rate and time to peak tidal flow as a proportion of total expiratory time (tPTEF:tE) were significantly diminished in index as compared with control infants (-4.0 breaths/min [-7.6, -0.4 breaths/min], versus -0.035 [-0.066, -0.005], respectively). These findings suggest a better prognosis for infant lung function after acute bronchiolitis than reported previously. Longitudinal studies are needed to clarify whether subclinical alterations in airway function precede acute bronchiolitis.     

Breast feeding for prevention of viral acute respiratory diseases in infants]

The incidence of acute viral respiratory diseases (confirmed by immunofluorescence test) was compared in a group of 159 infants aged 0-9 months breast-fed at least once daily and in a group of 608 infants of similar age and hospitalization duration receiving only artificial food. The incidence was significantly lower in breast-fed infants (p = 0.00057), especially in the first trimester of life (p = 0.00039). This was valid of all RSV infections (p = 0.01854) and parainfluenza type 4 virus infections (p = 0.0846). The antibody level against parainfluenza type 1 and 3 (HI) and against RSV in IgA class (ELISA) was compared with that in mother's milk and serum. No significant correlation was found for parainfluenza type 1 antibodies (r = 0.159) and 3 (r = 0.025), while for RSV the correlation was positive and statistically significant though rather low (r = 0.234). No significant correlation was found between milk antibody levels and the incidence of acute viral respiratory infections. Breast-feeding showed a significant influence on the lower incidence of these infections, particularly in the first trimester of life. It seems that this was associated with a non-specific mechanism rather than with the milk levels of specific antibodies.     

Interleukin-6 and small intestinal luminal immunoglobulins

Our aim was to determine the relationships between interleukin-6 and immunoglobulin levels within small intestinal luminal secretions. Twenty adult subjects with small intestinal bacterial overgrowth (N = 13), irritable bowel syndrome (N = 4), and nonulcer dyspepsia (N = 3) underwent endoscopic aspiration of secretions from the small intestinal mucosal surface for assessment of IL-6, IgA1, IgA2, IgM, IgG1, IgG2, IgG3, and IgG4 concentrations. Serum immunoglobulin concentrations and small intestinal histology were also determined. IgA2 and IgG3 were the predominant IgA and IgG subclasses in luminal secretions in 19/20 (95%) and 20/20 (100%) subjects, respectively. IgA1 and IgG1 predominated in serum in all subjects. No subject had villous atrophy. Luminal IL-6 concentrations correlated significantly with luminal IgA2, IgM, and IgG3 concentrations but not with IgA1 or any other IgG subclass levels. Conversely, luminal IL-6 or immunoglobulin concentrations did not correlate significantly with levels of any immunoglobulin isotype in serum. These observations suggest that important relationships exist between local IL-6 and IgA2, IgM, and IgG3 responses in human small intestinal luminal secretions. Local investigation is mandatory when assessing intestinal immune activity.     

Reduced serum IgG reactivities with bacteria from dental plaque in HIV-infected persons with periodontitis

Serum samples were obtained from 44 HIV-seropositive (HIV+) and 37 HIV-seronegative (HIV-) persons that were grouped according to periodontal status. Serum IgG and IgA reactivities towards Streptococcus mutans, Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis. Prevotella intermedia, Prevotella nigrescens and Fusobacterium nucleatum were measured by means of ELISA. HIV+ persons with chronic marginal periodontitis showed significantly lower IgG reactivities to the periodontal pathogens A. actinomycetemcomitans, P. gingivalis, P. intermedia and F. nucleatum as compared with their HIV- counterparts (p < 0.05). Specific serum IgA reactivities were similar in the two periodontitis groups, except for P. nigrescens where the HIV+ group with chronic marginal periodontitis had lower values than their systemically healthy counterparts (p < 0.05). The results indicate that HIV infection affects the humoral serum immune responses against bacteria in dental plaque; the depressed antibody responses may contribute to the increased susceptibility for periodontal infections in HIV-infected patients.     

IgA levels and carrier rate of pathogenic bacteria in 27 children previously tonsillectomized

The object of the present paper is to present laboratory and clinical data on 27 children of ages between 6 and 11 years, who in connection with tonsillectomy 2 1/2 years earlier had been found to have low serum and saliva IgA levels, low serum IgE levels, and a considerable lack of IgA and IgE plasma cells in the excised tonsils; correlation between deficiency in IgA and culture of pathogenic bacteria from the tonsils was significant. From a clinical point of view, 22 of the children had benefit of the tonsillectomy and had no longer a tendency towards a development of recurrent infections. The remaining 5 patients continued to complain of recurring respiratory infections; in addition, levels of serum and saliva IgA were low. Furthermore, 4 or these 5 children harboured pathogenic bacteria in their throats. Many of the 27 patients still had low serum IgA and IgE levels as compared with levels in healthy, age-related controls; in 3 patients, however, the IgE levels in serum had risen considerably parallel with the development of atopic diseases. Saliva IgA was rather constant after tonsillectomy as compared with the preoperative levels, though it had risen in some of the children. As regards serum IgG and IgM, these immunoglobulins had decreased significantly, and the question is raised, whether it might had been due to the tonsillectomy, either by the removal of chronically infected organs or by the removal of important immunological tissue.     

Phagocyte dysfunction in common variable immune deficiency

The history of a 13-year old boy is reported who suffered from frequent bacterial, enteroviral, and protozoal infections since late infancy. A decrease in the serum levels of IgG2, IgG3, IgA, a neutrophil dysfunction, and a partial cellular immune deficiency could be demonstrated. A deficiency of folic acid produced a pancytopenia which enhanced the patient's susceptibility to infections. The combined substitution of gammaglobulins and folic acid only was able to break this vicious cycle.     

Immunoglobulin class and subclass distribution of antibodies reactive with the immunodominant antigen of Actinobacillus actinomycetemcomitans serotype b

The aims of this study were to determine the immunodominant antigens of Actinobacillus actinomycetemcomitans serotype b (Aab) for the different immunoglobulin (Ig) classes and subclasses and to determine the relative levels of these different Igs in serum. Seropositive early-onset periodontitis patients were sampled, and the Ig classes IgG, IgA, and IgM and subclasses IgG1, IgG2, IgG3, IgG4, IgA1, and IgA2 were studied. Reactivity with Aab antigens was assessed by using the Western blot (immunoblot) in limiting dilution analysis and radioimmunoassay with sera from 13 early-onset periodontitis subjects. A smeared antigen in the upper portion of the immunoblots, typical of high-molecular-weight LPS, was immunodominant for IgG, IgA, IgM, IgG1, IgG2, IgG3, IgA1, and IgA2. This smeared antigen was present in every patient for all of these Igs at the endpoint. A few additional antigens were also present at the endpoint in some patients, but none were present in more than half of the subjects. The distribution of antibody titers by Ig classes reactive with the Aab immunodominant antigen was IgG > IgA > IgM. The distribution of antibody titers by IgG subclass was IgG2 > IgG1 approximately IgG3. Further quantitation by radioimmunoassay revealed that the mean concentration of IgG2 (65.7 micrograms/ml) was significantly greater than that of IgG1 (8.8 micrograms/ml). The IgA subclass distribution was IgA1 > IgA2, with IgA1 apparently being second only to IgG2. Therefore, the Aab antigen eliciting the highest antibody level in virtually all Ig classes and subclasses appeared to be lipopolysaccharide, and IgG2 was markedly elevated over all other serum Ig classes or subclasses reactive with Aab.     

Brushing abrasion of eroded dentin after application of sodium fluoride solutions

OBJECTIVE: To examine the relationship between immunological variables and the different types and severity of malnutrition in Ghanaian children. DESIGN: Case-control study. SETTING: The study was done at Princess Marie Louise Hospital, Accra, Ghana. SUBJECTS: One hundred and seventy children, aged 8-36 months, were recruited at the clinical ward and public health service section of the hospital: 61 normal children, 49 moderately malnourished (underweight) children and 60 severely malnourished children (19 kwashiorkor, 30 marasmus, and 11 marasmic kwashiorkor children). METHOD: The children underwent clinical observations, anthropometric measurements and blood sampling for biochemical analysis to evaluate their nutritional and immunological status. Serum immunoglobulins (IgA subclasses, IgG subclasses and IgM), complements (C3 and C4) and lymphocyte subpopulations (T cells, B cells, CD4+, CD8+, NK cells and HLADR) were determined for the assessment of humoral and cell-mediated immunity. RESULTS: Serum levels of IgA1, IgA2 and C4 tended to be higher in severely malnourished children than in normal children, while serum level of C3 and the proportion of B cells were significantly lower in the severely malnourished children than in the normal children (P < 0.05). There were no notable differences in most immunological parameters among the three severely malnourished groups. No differences were observed in the immunological parameters except for the proportion of B cells between normal and moderately malnourished children. Factor analysis revealed that C3 levels were positively correlated with a factor which was strongly associated with weight-for-height z-score and biochemical indicators for evaluating protein nutrition. In addition, IgA2, IgG1 and IgM levels were positively correlated with a factor which was associated with C-reactive protein. CONCLUSION: Several immunological variables responded positively or negatively with the different levels of severity of malnutrition, but most variables did not on the different types of malnutrition. The changes of C3 level were more associated with the severity of malnutrition.     

Changes in serum immunoglobulin levels during phenytoin treatment of epilepsy

Immunoglubulin concentrations were determined by radial immunodiffusion in sera from 15 epileptic patients before and during phenytoin therapy. Three reaction patterns were recorded: Two patients developed IgA deficiency (less than 0.05 mg/ml) during the first 3-4 months of treatment. Both patients also had a decrease in serum IgG and IgM, but no significant fall or increase in serum IgE. The IgA deficiency state was apparently reversible, since normalization of serum levels occurred after withdrawal of phenytoin. Five patients developed a 35-80 per cent reduction in serum IgA. In these patients, the decline in serum levels of IgG and IgM was inconsistent. Eight patients showed no significant fluctuations in serum immunoglobulins during phenytoin treatment. When a fall in serum IgA occurred, it did not correspond to a fall in serum or in red cell folate. Mean serum IgG was lower (9.37 mg/ml) in epileptic patients who had taken phenytoin for less than 1 year and had a low IgA, than in patients who had taken phenytoin for 10 years or more (11.50 mg/ml).     

Respiratory syncytial virus infection in childhood

Respiratory syncytial virus is the most frequent cause of respiratory tract infections in infants and is responsible for annual winter epidemics of acute bronchiolitis. Over the last decades medical therapy has remained unchanged and controversial, despite intensive research. Inhaled bronchodilators are often not effective and should be discontinued if no beneficial response can be documented. Steroids and ribavirin are not indicated in previously healthy infants with acute RSV bronchiolitis. There is some evidence, however, that certain risk groups may benefit from their use. With good supportive care the mortality from RSV infection is now low. Postinfectious alterations in lung function are usually transient and reversible. High-risk infants can be protected from severe RSV infections by monthly infusions of RSV immune globulins. This treatment modality has, however, not gained wide acceptance because of the benign nature of the disease and the high costs and side effects of regular immune globulin infusions. An international consensus statement on the treatment of RSV bronchiolitis may help to reduce the wide differences in clinical practice.     

Young Malaysian children with lower respiratory tract infections show low incidence of chlamydial infection

OBJECTIVE: The incidence of Chlamydia pneumoniae and Chlamydia trachomatis infection was studied among infants and young children admitted to hospital for the management of lower respiratory tract infections, over a 12 month period. METHODOLOGY: Respiratory secretions were examined for chlamydiae by cell culture, enzyme-linked immunosorbent assay and polymerase chain reaction-enzyme immunoassay. Sera were tested by micro-immunofluorescence for chlamydial IgG, IgM and IgA. Other bacterial and viral pathogens were also looked for by standard cultural and serological methods. RESULTS: Of 87 patients aged 2 months-3 years, an aetiologic diagnosis was made in 41 (47.1%). C. pneumoniae and C. trachomatis were each detected in 1 (1.2%) of the patients. Among common bacterial pathogens, Haemophilus influenzae (13.8%) and Streptococcus pneumoniae (8.1%) were the most frequently identified. Respiratory viruses and elevated Mycoplasma pneumoniae antibodies were found in 10.3% and 9.1% of patients, respectively. CONCLUSION: Chlamydiae are infrequent causes of community-acquired acute lower respiratory tract infections in infants and very young children in Malaysia.     

Evidence for differential effects of sulphasalazine on systemic and mucosal immunity in rheumatoid arthritis

OBJECTIVE: To study the effects of sulphasalazine (SASP) on the systemic and mucosal humoral immune systems in patients with rheumatoid arthritis (RA). METHODS: Serum concentrations of interleukin 6 (IL-6), class and subclass specific IgG, IgA and IgM, IgA and IgG antigliadin antibodies and rheumatoid factors (RF) of IgG, IgA (including IgA1 and IgA2 subclasses) and IgM isotypes were measured before and 16 weeks after sulphasalazine (SASP) therapy in 15 female and three male patients with RA. Amounts of immunoglobulins in saliva and jejunal fluid were measured as estimates of mucosal humoral immunity. RESULTS: Serum concentrations of IgA and IgG decreased significantly during SASP therapy and correlated with reduced concentrations of IL-6. In addition, levels of circulating IgA RF, IgA anti-gliadin antibodies and IgM RF decreased significantly after the treatment. In contrast, immunoglobulin levels in saliva and jejunal fluid were unaltered. CONCLUSION: SASP exerts powerful but selective inhibitory effects on systemic immunoglobulin production, whereas no effects on mucosal immunoglobulin production were observed. The decreased systemic B cell activity may be mediated by downregulation of the production of IL-6, a cytokine with Ig switching properties.     

Increased serum IgD concentrations in children with Henoch-Sch?nlein purpura

Serum IgD concentrations were measured in 39 children with Henoch Schonlein purpura (HSP) and 40 control children by means of radial immunodiffusion. Serum IgG, IgA and IgM concentrations in the HSP patients were measured by nephelometry. The geometric mean IgD concentration in children with HSP (16.7 microg/ml) was significantly higher than in control children (9.1 microg/ml; P=0.03). Serial testing in 10 HSP patients revealed no significant change in IgD concentrations over periods ranging from 1 to 12 months. There was no relationship between IgD and IgA concentrations in the HSP patients. Nineteen of the 39 HSP patients (49%) had nephritis. The mean IgD concentration in patients with nephritis (10.7 microg/ml) did not differ from control values, but was significantly lower than the mean IgD level in the remaining 20 patients who did not have nephritis (25.4 microg/ml; P=0.02). These results indicate that serum IgD levels are increased in children with HSP who did not have nephritis. IgD concentrations in patients with nephritis were similar to levels in control children.     

Clinical implications of IgA rheumatoid factor subclasses

OBJECTIVES: To evaluate the diagnostic and pathogenetic significance of IgA rheumatoid factor (RF) subclasses in rheumatoid arthritis (RA). METHODS: Rheumatoid factors of the IgA class and IgA1 and IgA2 subclasses were measured by enzyme linked immunosorbent assay in 58 patients with RA, 31 patients with other rheumatic diseases, 30 non-rheumatic individuals with increased concentrations of IgA RF, and in 100 randomly selected healthy controls. RESULTS: Using a 95% cut off for the controls, 55% of the RA patients had increased total IgA RF, 64% IgA1 RF, and 60% IgA2 RF. RA patients with extraarticular manifestations more often had increased concentrations of IgA RF and both subclasses than patients without such manifestations (p < or = 0.01). Nearly all (31/32) RA patients with increased IgA RF had increases in both IgA RF subclasses, compared with 67% (20/30 of nonrheumatic symptom free individuals with increased IgA RF (p = 0.002). CONCLUSION: Increased concentrations of the IgA2 RF subclass appears to be more specific for RA than increased IgA1 RF. Measurement of IgA RF subclasses may be clinically useful.     

IgG subclass levels in patients with B cell chronic lymphocytic leukaemia

Patients with B-cell chronic lymphocytic leukaemia (BCLL) have low levels of serum IgG. In order to determine if this is a pan IgG deficiency or a selective suppression of one or more IgG subclasses, levels of IgG 1, 2, 3 and 4 in nine BCLL patients were determined and compared to those of nine age and sex matched controls. No significant differences were found in the levels of IgG1 and IgG2, but the patients were found to have significantly lower levels of IgG3 (p < 0.05) and IgG4 (p < 0.05). Selective deficiencies of these isotypes may explain the particular pattern of infection seen in BCLL patients.     

Elastin-derived peptides and anti-elastic antibodies in children with recurrent or obstructive bronchitis

The aim of the study was to examine the effects of bronchitis on elastin-derived peptides (EP) and antielastin antibodies (AEAb) in serum. Using an ELISA technique, these parameters were assessed in children aged 6 months to 15 years: 36 had recurrent bronchitis (RB), 34 had obstructive bronchitis (OB) and 37 were healthy children (C). A comparison of the levels of the investigated compounds in the acute phase (I) and stage without signs of diseases (II) was studied. The EP data show non-significant changes in the RB and OB groups in comparison with group C. Children with OB had significantly lower levels of AEAb in IgA, IgG and IgM class antibodies, while those with RB in the IgG class in comparison with group C in both examinations. In examination 1, AEAb in IgA and IgM classes were significantly lower in children with OB than with RB.     

Studies on the action of interleukin-1 on term human fetal membranes and decidua

The present study describes the development of an enzyme-linked immunosorbent assay capable of quantifying serum antibody of all four canine IgG subclasses. A panel of subclass-restricted and subclass-specific monoclonal antibodies was used to measure IgG subclasses in the serum of healthy dogs, as well as in dogs with a range of clinical diseases. The subclasses have been redefined as IgG1, IgG2, IgG3 and IgG4 based on a comparison with the relative concentration and electrophoretic mobilities of human IgG subclasses. In serum samples from healthy dogs, the concentration of IgG1 (mean, 8.17 +/- 0.95 mg ml-1) and IgG2 (mean, 8.15 +/- 3.16 mg ml-1) were very similar and considerably higher than the levels of IgG3 (mean, 0.36 +/- 0.43 mg ml-1) and IgG4 (mean, 0.95 +/- 0.45 mg ml-1). There was no apparent difference in the level of subclasses between the different breeds comprising this normal population. Sera from dogs with a range of immune-mediated or inflammatory diseases all had markedly elevated levels of IgG2 (more than 13 mg ml-1), but IgG1 decreased (less than 4 mg ml-1) to levels below the normal range.