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PubMed1991

Isotype distribution of mucosal IgG-producing cells in patients with various IgG subclass deficiencies.

The subclass distribution of IgG-producing immunocytes was examined by immunohistochemistry in nasal and rectal mucosa of infection-prone patients with untreated IgG subclass deficiencies. Biopsy specimens from the two sites were obtained in 18 clinically and serologically well-characterized adult subjects; only a nasal or rectal sample was available from nine similar patients. Chronic lung disease was common in the patient groups with selective serum IgG1 deficiency and combined IgG1 and IgG3 deficiency, whereas the other categories of patients had mainly upper airway and other mild infections. Serum IgG2 or IgG3 deficiency was usually expressed also at the cellular level in rectal mucosa, and the proportion of rectal IgG1 cells was significantly correlated with the IgG1 level (r = 0.90, P less than 0.001). Likewise, there tended to be a decreased expression of the actual subclass at the cellular level in nasal mucosa of patients with serum IgG1 or IgG2 deficiency. Conversely, the median nasal proportion of IgG3 cells was remarkably unaffected by a deficiency of this subclass in serum and rectal mucosa. Interestingly, these patients rather tended to have raised IgG3 and reduced IgG2 cell proportions in their nasal mucosa, although this apparent local IgG3 compensation was nevertheless strongly correlated with the serum IgG3 level (r = 0.87, P less than 0.002). These disparities may reflect different antigenic and mitogenic exposure of the two tissue sites; for example, a persistent protein bombardment of the nasal mucosa that could conceivably override locally a B cell maturation defect. The possible clinical consequences of such variable mucosal expression of IgG subclass deficiencies remain to be studied.

Adult↗
PubMed1986

IgG subclass deficiencies: identifying and treating patients at risk.

IgG subclass deficiencies can increase the risk of pulmonary infections or other severe recurrent infections. Various groups of patients were studied in an attempt to learn more about (1) measuring the IgG subclass levels (particularly IgG4 levels) of possible high-risk patients; (2) identifying those patients who are at risk of developing recurrent infections, and (3) treating these patients once they have been identified. Individual cases are presented, and associations of isolated subclass deficiencies are examined with respect to infection. Replacement therapy with plasma or intravenous immunoglobulin (IVIG) to increase titers of deficient or absent subclasses is suggested.

Dysgammaglobulinemia↗
PubMed1979

Staphylococcus aureus opsonization mediated via the classical and alternative complement pathways. A kinetic study using MgEGTA chelated serum and human sera deficient in IgG and complement factors C1s and C2.

Staphylococcus aureus opsonization was studied kinetically by: (1) determination of the uptake of [3H]-thymidine labelled bacteria by human PMN's; (2) fluorescent anti-C3 and anti-IgG staining of opsonized bacteria; and (3) measuring bacterial complement consumption. Maximum opsonization in normal serum occurred within 5 min of incubation. About 80% of staphylococci were then taken up by PMN's, and IgG and C3b could be detected on the bacterial surface. In the absence of a functional classical complement pathway, as in sera deficient in C1s and C2 and in MgEGTA chelated serum, maximal opsonization was only achieved after 30--60 min incubation. Opsonization in IgG deficient serum occurred at a rate similar to that found in C2 deficient or MgEGTA chelated serum. Opsonization was greatly enhanced when sera were reconstituted. It was concluded that in IgG deficient serum Staphylococcus aureus opsonization is mediated via the alternative complement pathway. Dilution of normal serum primarily affected the classical complement pathway, resulting in a decreased rate of opsonization. In normal serum IgG did not appear to be a rate-limiting factor. S. Aureus opsonization was best studied by the phagocytosis assay and the fluorescent-antibody technique. Measuring haemolytic complement consumption was found to be an insensitive indicator of bacterial complement activation and opsonization.

Complement Activation↗
PubMed1992

IgG subclass deficiency associated with corticosteroids in obstructive lung disease.

IgG subclass levels were measured in three groups of adult patients with obstructive airways disease to discern the relationships among depressed IgG subclass levels, chronic corticosteroid use, and recurrent sinopulmonary infections. Group 1 consisted of patients with corticosteroid-dependent bronchial asthma, group 2 patients had corticosteroid-dependent chronic bronchitis/emphysema, and group 3 was comprised of asthma patients not requiring oral corticosteroids but associated with recurrent sinopulmonary infections. One or more IgG subclass deficiencies were noted in 66.7 percent of group 1, 46.7 percent of group 2, and 6.7 percent of group 3. Significant differences were noted between groups 1 and 3 (p = .0008) and between groups 2 and 3 (p = .018), but not between groups 1 and 2 (p = .5). IgG1 deficiency was the most common subclass deficiency found; 14 (77.8 percent) of 18 patients with detectable subclass deficiency demonstrated IgG1 deficiency. In this study population, IgG subclass level deficiencies appeared to be secondary to long-term low-dose corticosteroid therapy.

Adrenal Cortex Hormones↗
PubMedDate not supplied

IgG subclass deficiency in children with recurrent infections.

IgG subclass levels were studied in 12 children, aged between 2.5-12 years with recurrent respiratory tract infections. They did not have low IgG levels or IgA deficiency. We found combined deficiency of IgG2-IgG4 in one patient and selective IgG2 deficiency in another (16.6% of patients). These two patients had bronchiectasis due to recurrent severe pneumonia, however one patient with bronchiectasis had normal IgG subclass concentrations. Our IgG subclass-deficient patients who did not respond to prophylactic antibiotic therapy were given gammaglobulin therapy. IgG subclass deficiency should be considered in children with unexplained recurrent infections even in the presence of normal serum immunoglobulin levels.

Child↗
PubMed1993

Deficiency of IgG subclass antibody response to tetanus toxoid associated with high serum IgA levels in IgA nephropathy.

In order to investigate IgG subclass response in IgA nephropathy (IgAN), 20 patients and 20 age and sex matched controls were systemically immunized with tetanus toxoid (TT). Nineteen/20 controls and 19/20 IgAN made a serum IgG anti-TT response of similar magnitude. However, significantly more patients with IgAN had undetectable amounts of at least one IgG subclass antibody to this antigen than controls (7/19 IgAN, 1/19 controls, p < 0.05). All individuals with an IgG subclass anti-TT deficiency lacked IgG1 and/or IgG4. Two patients made no IgG3 anti-TT (as well as no IgG1 and IgG4 anti-TT) but all individuals who responded to TT made IgG2 anti-TT. Total IgG subclass levels in IgAN did not differ from controls and no patient with IgAN had a total IgG subclass deficiency. Total serum IgA was significantly raised in IgAN (p < 0.002) and 6/7 IgAN with an IgG anti-TT subclass deficiency had a serum IgA level of over 3.2 milligrams compared to only 2/12 IgAN with no IgG subclass anti-TT deficiency (p < 0.01). The association of high serum IgA levels with IgG subclass deficiency to TT may be due to an abnormality in switching from IgG to IgA production in IgAN, or a manifestation of a defect of immunoregulation analogous to that proposed in IgA deficiency.

Adult↗
PubMed2002

IgG and IgG subclasses deficiency in children undergoing continuous ambulatory peritoneal dialysis and its provocative factors.

BACKGROUND: Low levels of serum IgG or IgG subclasses may be responsible for the defective peritoneal defense and for peritonitis attacks in continuous ambulatory peritoneal dialysis (CAPD) children. Malnutrition, peritoneal loss or frequent peritonitis may lead to IgG or IgG subclasses deficiency. METHODS: Levels of IgG subclasses were determined in 12 children undergoing CAPD treatment. Radial immunodiffusion technique was used for determination. Patients were aged from 6 to 16 years (mean age 12.3 years) and had been on CAPD for 11-26 months (mean duration 19.4 months). We evaluated whether IgG and IgG subclasses deficiency are related to malnutrition, the peritonitis rate and the duration of CAPD using the SPSS program. RESULTS: Serum total IgG levels were found to be low in eight out of 12 patients. Eight patients showed low levels of IgG1, four patients IgG2, one patient IgG3 and three patients IgG4. Total IgG values were found to be positively correlated to malnutrition status, peritonitis rate and duration of CAPD. The IgG2 values were found to be related to the duration of CAPD. The IgG4 values were found to be correlated to the peritonitis rates. CONCLUSIONS: The IgG and IgG subclasses deficiency may develop in children while on CAPD treatment. Periodical determinations of either serum IgG or the subclasses may be useful in the follow-up of these patients.

Adolescent↗
PubMedDate not supplied

Pneumococcal antibodies of different immunoglobulin subclasses in normal and IgG subclass deficient individuals of various ages.

The distribution of pneumococcal antibody activity of the IgG and IgA subclasses was determined in healthy individuals of various ages using monoclonal antibodies in an enzyme linked immunosorbent assay (ELISA). High IgG 2 antibody activity was found in cord blood and in serum from adults. IgG 1 activity was most pronounced in serum from young children and virtually lacking in serum from adults. Anti-pneumococcal antibodies were found to be low in IgG 2 deficient donors and normal in IgG 3 deficient donors. A maturation from relatively low IgG 1 and IgG 2 antipneumococcal activity in young children to high IgG 2 levels in adults was found in healthy individuals. IgA subclass antipneumococcal activity was correlated to age. Evaluation of the distribution of pneumococcal antibody activity of various subclasses offers a new possibility for studying the immune response to infection and immunization.

Adolescent↗
PubMedDate not supplied

The frequency of IgG subclass deficiency in children with recurrent respiratory infections.

We studied the frequency of IgG subclass deficiency in 61 children (ages 1-7 years, mean 3.8 years) with recurrent respiratory tract infections by using the radial immunodiffusion method. The overall frequency of IgG subclass deficiency was found to be 39.3 percent (24 patients). Among 26 children who had major immunoglobulin abnormalities, we found IgG subclass deficiency in 11 patients (42.3%). In children with normal immunoglobulin levels, the frequency of IgG subclass deficiency was 37.1 percent (13 patients).

Child↗
PubMed1988

[IgG subclass deficiency in childhood. Changes in the antigen specific immune response and significance of low IgG4 level].

The definition of IgG subclass deficiency and the correlations between low IgG subclass serum concentrations and high incidence of infections in certain patients are still obscure. Therefore 260 children from 6 months to 18 years with severe recurrent infections or a known immunodeficiency were screened for IgG subclass deficiency. Nine patients with severe IgG2 deficiency (Ig2 less than 0.3 g/l) and 35 patients with non-detectable IgG4 in immunoprecipitation were detected. One of these patients had a concomitant IgA deficiency, eight revealed an additional IgA and IgG2 deficiency, two an IgA, IgG2, and IgG3 deficiency, eighteen an IgG2 deficiency and one patient an IgG2 and IgG3 deficiency. The proportion of patients with non-detectable IgG4 in immunoprecipitation was 13.5% and thus in the same order of magnitude as described in the literature for healthy people. Our data show that there is no relation between low IgG4 serum levels and the increased occurrence of severe infections. In all patients investigated with non-detectable IgG4 in immunoprecipitation the gene for the heavy chain gene constant domain C gamma 4 could be detected by Southern blotting. Using a sensitive ELISA method IgG4 could be directly demonstrated in all patients at a serum level of 0.5-29 micrograms/ml. Specific IgG4 antibodies against protein antigens could not be detected in IgG4-deficient patients. Nevertheless total IgG antibodies against diphtheria and tetanus toxoid reached protecting titers. Patients with IgG2 deficiency showed an impaired immune response against polysaccharides from pneumococci and haemophilus influenzae type b.

Adolescent↗
PubMed2005

IgA and/or IgG subclass deficiency in children with recurrent respiratory infections and its relationship with chronic pulmonary damage.

Most patients with IgA and/or IgG subclass deficiency are asymptomatic but some may suffer from frequent mainly respiratory infections. The aim of our study was to determine the frequency of IgA and/or IgG subclass deficiencies and the rate of chronic pulmonary damage secondary to recurrent pulmonary infections in these children. Serum IgA and IgG subclass levels were measured in 225 children aged 6 months to 6 years with recurrent sinopulmonary infections (44 with recurrent upper respiratory tract infections, 100 with recurrent pulmonary infections and 81 with recurrent bronchiolitis). In order to determine chronic pulmonary damage due to recurrent infections in patients with recurrent pulmonary infections CT scans of thorax were also obtained. The overall frequency of antibody defects was found to be 19.1%. IgA deficiency was observed in 9.3%, IgG subclass deficiency in 8.4% and IgA + IgG subclass deficiency in 1.4%. The prevalance of IgA and/or IgG subclass deficiency was 25% in patients with recurrent upper respiratory tract infections, 22% in patients with recurrent pulmonary infections and 12.3% in patients with recurrent bronchiolitis (p>0.05). Chronic pulmonary damage in lungs was determined radiologically in 17 of 100 cases with recurrent pulmonary infection. In IgG subclass deficiencies sequel changes, although not statistically significant, were observed five times more frequently than that of IgA deficiencies. CT scans revealed pulmonary sequels in 5 of the 22 (22.7%) patients with recurrent pulmonary infections and immunodeficiency (bronchiectasis in 2 patients with IgG3 deficiency, fibrotic changes in one with IgA deficiency and in one with IgG3 deficiency, bronchiolitis obliterans in one with IgG2 + IgG3 deficiency). On the other hand, pulmonary sequels were observed in 12 patients (15.4%) with normal immunoglobulin levels. Eight of them were bronchiolitis obliterans, 2 of them were atelectasia and 1 of them was bronchiectasia. We therefore suggest that determination of antibody levels and evaluation of pulmonary alterations is crucial in patients with recurrent sinopulmonary infections since the deficiency of antibodies is associated with a greater pulmonary damage.

Bronchiolitis↗
PubMed1998

[Intravenous immunoglobulin (GB-0998) for prophylaxis of recurrent acute otitis media and lower respiratory tract infection in infancy with IgG 2 deficiency].

The prophylactic effect of intravenous immunoglobulin (GB-0998) on the recurrent acute otitis media, bronchitis and bronchopneumonia in IgG 2 deficient infants was investigated in a multicenter trial. GB-0998 was administered 6 times every 4 weeks. The doses were 300 mg/kg wt. during the first treatment, followed by 5 doses of 200 mg/kg wt. The results indicated that GB-0998 was effective in the prophylaxis of the recurrent infection of acute otitis media, bronchitis and bronchopneumonia in infancy with IgG 2 deficiency and/or IgG 2 antibody deficiency specific for Streptococcus pneumoniae.

Acute Disease↗
PubMed1986

IgG subclass deficiency in children with IgA deficiency presenting with recurrent or severe respiratory infections.

A group of 22 children presenting with recurrent or severe respiratory tract infections who had low IgA levels (more than 2 SD below the mean for age) were examined for IgG subclass deficiency. Patients were screened for possible defects in neutrophil chemotaxis, bactericidal, fungicidal, and quantitative iodination activity, as well as for complement function. The majority of the patients showed IgG subclass levels below the mean for age. Nine of the children showed definite IgG subclass deficiency and at least two showed definite deficiency of more than one IgG subclass. The predominant subclass deficiency was found to be IgG1. While nine children showed IgG4 levels below the level detectable by the technique used, it is not possible to assess whether these patients are deficient in this isotype since some healthy subjects also give values below the level of detection. Most of the patients who had very low (1-6 mg/dl) or undetectable (less than 1 mg/dl) levels of serum IgA did not show IgG subclass deficiencies, while IgG subclass deficiencies were common among those with borderline low IgA levels (slightly more than 2 SD below the mean for age). Nine children showed total IgG levels close to 2 SD below mean for age, and at least six of these showed IgG subclass deficiency. The result suggests that patients with recurrent and/or severe respiratory infections who have borderline IgA and IgG levels may have IgG subclass deficiencies and if they do could benefit from immunoglobulin therapy.

Blood Bactericidal Activity↗
PubMed1996

Hodgkin's disease associated with IgA and IgG subclass deficiency.

Cases of cancer have been reported in patients with primary humoral immunodeficiency syndromes, mainly non-Hodgkin's lymphoma and gastric adenocarcinoma. Two cases of Hodgkin's disease complicating IgA and IgG subclass deficiency are reported. This association is probably more than mere coincidence. A review of the literature is presented.

Adult↗
PubMed1985

Recurrent sinopulmonary infection and impaired antibody response to bacterial capsular polysaccharide antigen in children with selective IgG-subclass deficiency.

We studied 20 children with recurrent sinopulmonary infections and serum IgG levels within the normal range, who had selective IgG-subclass deficiency. Twelve of the children were IgG2 deficient, five were IgG3 deficient, and three were deficient in both IgG2 and IgG3. IgA deficiency was present in 3 of the 20 patients. In the children with IgG2 deficiency, serum antibody concentrations to the capsular polysaccharide of Hemophilus influenzae type B (Hib) were significantly lower than those in age-matched controls, both before and after immunization with the Hib capsular polysaccharide antigen, which elicits antibody predominantly of the IgG2 subclass. In contrast, their serum antibody titers to the tetanus and diphtheria toxoid protein antigens, which elicit antibody predominantly of the IgG1 subclass, were normal in comparison with those of age-matched controls. These results suggest that impairment of the antibody response to specific microbial antigens predisposes patients with selective IgG-subclass deficiencies to recurrent infections. Thus, as an aid in determining therapy, children with recurrent infections and normal total serum IgG should be evaluated for this condition.

Adolescent↗
PubMed1988

IgG subclass deficiency in asthma.

Total immunoglobulin G (IgG) and subclasses were measured in serum samples from 82 children with chronic asthma, aged 1.5 to 6.3 years, and 76 controls. Concentrations of IgG1, IgG2, IgG3, and total IgG were significantly lower in asthmatic children aged 1 to 5, and IgG2 concentrations were also significantly lower in asthmatic children over 5 years of age. Twenty eight asthmatic children had at least one value in the deficient range, and 26 had IgG2 deficiency alone or in combination. Five children had IgG2 and IgA deficiency. These 28 children were significantly younger and fewer had raised IgE concentrations than the remainder. IgG subclass deficiency, which may reflect delayed maturation of the immune system, is common in young asthmatic children, and may have a role in the pathogenesis of the disease.

Asthma↗
PubMed1994

Qualitative and quantitative analyses of the antibody response elicited by Haemophilus influenzae type b capsular polysaccharide-tetanus toxoid conjugates in adults with IgG subclass deficiencies and frequent infections.

Twenty-one IgG subclass-deficient adult patients with repeated infections of the respiratory tract, were immunized with Haemophilus influenzae type b capsular polysaccharide (HibCP) covalently bound to tetanus toxoid (TT). Specific immunoglobulin and IgG subclasses to HibCP and TT were quantified; the biological activities of HibCP antibodies were also investigated. Most patients showed an antibody response similar to that observed in healthy adults, and the bactericidal activity related to the post-immunization levels of HibCP antibodies. No relation was found between immunoglobulin isotype deficiency, the clinical symptoms and the IgG subclass responsiveness, and no relation was observed between HibCP and TT antibody responses. Our data indicate that some, but not all, patients with recurrent infections and IgG subclass deficiency have an abnormal serum antibody response to polysaccharide and protein epitopes of Hib-TT conjugate vaccine. Analysis of the antibody response after vaccination with HibCP-TT conjugate vaccine did not seem to predict the clinical course of such patients.

Adult↗