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Biomedical subjects

M A Avanzini

Publications and source records attributed to M A Avanzini.

At least 37 records · Page 2Linked to original sources

Clinical aspects of coeliac disease in children with insulin-dependent diabetes mellitus.

Coeliac disease (CD) is heterogeneous in its clinical presentation and pathological expression. Silent, latent and potential forms represent the submerged part of the so-called "coeliac iceberg". The association of insulin-dependent diabetes mellitus (IDDM) and CD has been widely reported. For the screening of CD in diabetic patients, anti-reticulin R1 (ARA-R1) and anti-endomysium (AEA) antibodies are more reliable markers than anti-gliadin (AGA) antibodies. Recent studies have reported an increased prevalence of CD in children with IDDM. In our experience intestinal biopsy confirmed a diagnosis of CD in 6 out of 172 diabetic patients, with a prevalence of 3.5%. Only occasionally does CD precede the onset of IDDM; more often CD is diagnosed shortly or sometimes years after the onset of diabetes. Typical gastrointestinal complaints of CD (such as diarrhoea, abdominal distension) are rare in IDDM patients, while atypical isolated signs or symptoms of CD are more common, in particular sideropenic anemia, short stature, delayed puberty, epilepsy, hypertransaminasemia, dyspeptic symptoms, herpetiform dermatitis, and recurrent aphthous stomatitis. It is recommended that all diabetic children, even those asymptomatic, should be screened yearly for CD, using a combination of AGA plus ARA-R1 and AEA.

Adolescent↗

Antibody response to pneumococcal vaccine in children receiving bone marrow transplantation.

Fifty-three pediatric patients given an allogeneic or an autologous bone marrow transplantation (BMT) were immunized with a polyvalent pneumococcal capsular polysaccharide vaccine (Pneumovax II). Vaccine was administered six months or more after BMT and the pneumococcal IgM, total IgG, and IgG subclasses levels were evaluated before and three weeks after immunization. Immunization promoted a significant rise in antibody serum levels (P < 0.000001), and all children vaccinated more than two years after transplantation responded to pneumococcal polysaccharides, whereas only 20-30% and 50% of patients given BMT between six months and one year and one and two years, respectively, mounted an effective antibody production (P < 0.0001). In univariate analysis, lapse of time from BMT to vaccination, chronic graft-versus-host disease occurrence, and female sex influenced the response rate. However, in multivariate analysis, only time between marrow transplant and immunization was a powerful predictor of response. Interestingly, four of 11 patients with IgG2 deficiency before immunization normalized serum levels of this IgG subclass after the pneumococcal antigenic challenge. Our study suggests that time after transplant is the major factor influencing the recovery of immune reactivity to polysaccharide antigens. This seems to confirm the hypothesis that ontogeny of the B-cell repertoire follows a predetermined sequential program in which polysaccharide antigens are some of the last to evoke an antibody response.

Adolescent↗

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↗

Transient IgG subclass deficiencies in newly diagnosed diabetic children.

In 27 children (15 males and 12 females) with insulin-dependent diabetes mellitus (IDDM), aged 1.2-13.5 years (mean 9.9 +/- 3.6 years) we investigated immunoglobulins (IgG, IgA, IgM), IgG subclass levels and islet-cell antibodies (ICA) at diagnosis and at 6 and 12 months after disease onset. At diagnosis, IgG levels were lower than -2SD in 7 patients (26%), IgA in 1 (3.7%), IgM in 1 (3.7%). IgG subclass levels were below the 3rd percentile in 13 patients (48.1%); in particular IgG1 in 7 (26%), IgG2 in 3 (11.1%), IgG3 in 2 and IgG4 undetectable in 1 case. In 3 out of the 13 patients combined IgG1-IgG3, IgG1-IgG2 and IgG1-IgG4-IgA deficiencies were observed. ICA were greater than 20 Juvenile Diabetes Foundation units in 17/27 patients. The HLA-DR2 frequency was higher in patients with IgG subclass deficiency than in patients with normal IgG subclass levels. During follow up, IgG levels normalized in 6 patients while IgA and IgM did not change. IgG1 normalized in 5 out of the 7 patients, IgG2 in all patients while IgG3 and IgG4 did not change. One year later ICA were still present in 8/27 patients. The hypogammaglobulinaemia and IgG subclass deficiencies observed in our patients could have either a genetic or an acquired basis.

Adolescent↗

A comparison of secretory antibodies in breast-fed and formula-fed infants over the first six months of life.

In the present study salivary IgA, anti-Escherichia coli, anti-beta-lactoglobulin and anti-poliovirus type 1 IgA and IgM in serum and saliva were evaluated longitudinally in 13 breast-fed and 14 formula-fed infants over the first six months of life. Salivary IgA was quantified by electroimmunodiffusion; specific IgA and IgM antibodies were determined in serum and saliva by ELISA. Salivary IgA was significantly lower at age one month in breast-fed compared with formula-fed infants but in breast-fed infants salivary IgA increased with age and was significantly higher at six months than at one month. In both groups of infants, at the age of six months, salivary IgA levels were significantly lower than in adult controls. No significant differences in secretory anti-E. coli were observed between the two groups of infants. Salivary anti-poliovirus IgA and IgM antibodies increased transiently only to disappear in most babies at age six months, while anti-beta lactoglobulin IgA and IgM, present in saliva at all ages, showed a wide scatter. No important differences in specific serum IgA or IgM antibodies were observed either between the groups or at different times within the groups.

Age Factors↗

Immunoglobulin G3-specific antibodies as a marker for early diagnosis of HIV infection in children.

Early diagnosis of HIV infection in the child of an HIV-infected mother may be difficult as HIV-specific immunoglobulin (Ig) G antibodies are transmitted to the fetus transplacentally. In an attempt to provide a new, simpler tool for early identification of HIV-infected children we analysed the HIV-specific IgG subclass pattern during the first year of life. One hundred and one samples were collected from 35 children born to HIV-seropositive mothers, among whom 18 seroreverted during follow-up and 17 were HIV-infected (two P1 and 15 P2 according to the Centers for Disease Control classification). Serum HIV-specific IgG3 was detectable at least in one sample in 26 out of 35 children. All 17 HIV-infected children showed persistently detectable specific IgG3, both with stable or progressive disease. Out of the 18 uninfected children who seroreverted during follow-up, nine were HIV-specific IgG3-negative when first tested and nine lost HIV-specific-IgG3 within 28 weeks after birth. The correlation of the serological results with clinical information and any other diagnostic tool on each child suggests that the clearance of specific-IgG3 antibodies heralds seroconversion in uninfected passive antibody-carrier children. This observation provides the basis for a new, simple and effective method for early diagnosis of HIV infection in children born to seropositive mothers.

Biomarkers↗

Serum IgG subclass concentrations in healthy subjects at different age: age normal percentile charts.

IgG subclass levels were determined in 448 normal children from 6 months to 18 years of age and in 141 healthy adults by radial immunodiffusion using monoclonal antibodies. Age-normal percentile values were calculated for each year of age up to 18 years for IgG1, IgG2, IgG3 and in adults for all four subclasses. The broad spread of IgG4 values in children did not permit calculation of reference values.

Adolescent↗

Variation of serum IgG subclass concentrations with disease activity in juvenile chronic arthritis.

Nineteen patients with juvenile chronic arthritis were followed up and serum IgG subclass concentrations measured at different stages of disease activity. Patients were divided into three groups according to clinical activity of the disease: active disease, partial remission, and remission. The results were compared with normal values obtained in 448 healthy children aged 6 months to 18 years with a homogeneous distribution for each year of age. Serum IgG subclass concentrations of each child were first log transformed and then age corrected, taking the deviation of the log transformed value from that expected for a child of the same age. It was found that patients with partial remission had increased concentrations of IgG2 and decreased concentrations of IgG1 compared with patients with active disease. This suggests that the remission inducing process, at least in juvenile chronic arthritis, is accompanied by a switch of IgG subclass production.

Adolescent↗

Diagnostic value of a lymphocyte stimulation test in cow milk protein intolerance.

In order to evaluate the diagnostic value of a lymphocyte stimulation test with casein and beta lactoglobulin in cow milk intolerance (CMI), we studied 26 patients with a diagnosis of CMI and 25 age-matched controls with intestinal diseases other than CMI. Lymphocyte stimulation test to casein (P less than .001) and beta lactoglobulin (P less than .001) was significantly higher among CMI patients. Seventeen patients were RAST positive and nine negative for whole milk proteins. No differences were found in the lymphocyte stimulation test response between RAST-positive and RAST-negative subjects. These results suggest that lymphocyte stimulation test with highly purified antigens in optimal concentrations is specific and could be useful in the diagnosis of CMI.

Animals↗

IgG subclass deficiency in patients with Down's syndrome and aberrant hepatitis B vaccine response.

Seventeen adult patients with Down's syndrome (DS) and 19 adult healthy references were vaccinated with a hepatitis B vaccine in order to study the IgG subclass response. An enzyme-linked immunosorbent assay (ELISA) using monoclonal antibodies specific for IgG subclasses was employed. In spite of normal levels of total IgG1 and normal or even high levels of IgG3 in the DS patients, a significantly lower IgG1 response to the vaccine was observed in trisomic patients than in the references.

Antibody Formation↗

Comparison of the frequency of atopic diseases in children with severe and partial IgA deficiency.

Similar frequencies of atopic diseases and of elevated total serum IgE levels were observed in 40 children with serum IgA levels below 5 mg/dl and absence of salivary IgA (severe selective IgA deficiency, SIgAD) and in 40 children with serum IgA levels above 5 mg/dl but below -2 SD of age-normal mean values and presence of salivary IgA (partial SIgAD). These findings suggest that the absence of secretory IgA, which has been postulated to play a protective role by excluding allergens at the mucosal level, does not appear to play a crucial role in the pathogenesis of atopic diseases.

Agammaglobulinemia↗

IgG subclass serum levels in juvenile chronic arthritis.

IgG subclass levels of sera from 26 patients with juvenile chronic arthritis (JCA) were determined by means of mouse monoclonal antibodies. Patients were divided into three groups according to clinical activity of the disease: active disease, partial remission, and remission. One hundred and sixty four age matched, healthy children served as controls. IgG subclass concentrations were log transformed, and a robust regression method was applied to obtain expected values for the different ages. We found a significant increase of IgG3 (p less than 0.0001), IgG1 (p less than 0.002), and IgG2 (p less than 0.035) in JCA sera, while IgG4 values did not differ significantly from those of controls. When patients were divided according to clinical activity significant increases of IgG2 and IgG4 were observed in the patients in partial remission. Our data suggest that differential increase of IgG subclasses during the courses of JCA may be of relevance to the pathogenesis of the disease.

Adolescent↗