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Biomedical subjects

A Plebani

Publications and source records attributed to A Plebani.

At least 73 records · Page 4Linked to original sources
PubMed1993

Extensive deletion of immunoglobulin heavy chain constant region genes in the absence of recurrent infections: when is IgG subclass deficiency clinically relevant?

This report describes two children with undetectable serum levels of IgA1, IgG2, IgG4, and IgE due to a homozygous deletion encompassing the A1-E genes. The father is a heterozygous carrier of the same deletion and the mother a heterozygous compound carrying the deletion on one chromosome and duplication on the other. In both children, serum IgG, IgG1, and IgG3 were higher than in normal children and IgG antibody response to tetanus toxoid and polysaccharide antigens was normal with increased IgG1 and IgG3 response compared to controls. The latter can be interpreted as a compensatory mechanism for the subclass deficit and may explain the lack of significant infections in both children. The importance of distinguishing IgG subclass deficiency due to gene deletion from that due to immunoregulatory dysfunction is discussed.

Adolescent↗
PubMed1993

Familial clustering of IGHC deletions and duplications: functional and molecular analysis.

The human immunoglobulin heavy chain constant region locus (IGHC) comprises nine genes and two pseudogenes clustered in a 350 kilobase (kb) region on chromosome 14q32. Several IGHC haplotypes with single or multiple gene deletions and duplications have been characterized. The most likely mechanism accounting for these unusual haplotypes is the unequal crossing-over between homologous regions within the locus. Here we report the analysis of an unusual case of familial clustering of deletions/duplications. In the two branches of the BON family, three duplicated and two deleted haplotypes, all probably independent in origin, have been characterized. The structure of the haplotypes, one of which is described here for the first time, supports the hypothesis of homologous unequal crossing-over as the origin of recombinant haplotypes. The analysis of serological markers in a subject carrying one deleted and one duplicated haplotype allowed us the first direct inferences concerning the functions of the duplicated IGHC haplotypes.

Adolescent↗
PubMed1993

Early detection of IgA specific antibodies in HIV-1 infected children by peptide-ELISA and peptide time-resolved fluoro-immunoassay.

The presence of specific IgA antibodies in sera from 25 infants born to HIV-1 seropositive mothers was investigated by peptide-ELISA and peptide time-resolved fluoro-immunoassay (TR-FIA). The infants had been monitored at different times after birth for clinical signs and/or symptoms of HIV-1 infection and for detection of HIV-1 in lymphocyte cultures. Serum samples had also been tested for HIV-1 IgG antibodies by commercial ELISA and Western blot and for p24 antigen. Eleven of 25 children were then identified as infected. IgA detection was performed after rProtein G treatment to remove interfering IgG. In the infected group, IgA specific antibodies to a synthetic peptide representing a highly conserved region of the transmembrane glycoprotein gp41 (env: 594-613) were detected in 27 (73%) out of 37 serum samples (9 of 11 children) by the peptide-ELISA test. IgA specific antibodies to the same peptide were found in 30 (81%) sera (9 of 11 children) by the peptide-TR-FIA. Specific HIV-1 IgA antibodies were detected as early as 2 months of age in serum samples from five out of seven children (71% sensitivity) using peptide-ELISA and from six out of seven (86% sensitivity) by peptide-TR-FIA. Conversely, IgA specific antibodies to HIV-1 were absent in two infected children as well as in the sera of all uninfected children tested during the follow up period. Since maternal IgA does not cross the placenta, IgA detection in the serum of the infant is indicative of HIV-1 infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Enzyme-Linked Immunosorbent Assay↗
PubMed1993

B and T lymphocyte subsets in fetal and cord blood: age-related modulation of CD1c expression.

Peripheral blood lymphocytes from fetal, term and adult subjects were analyzed with a panel of B- and T-lymphoid differentiation markers. CD1c +ve and CD5 +ve B cell (IgM +ve) percentage in fetal, cord and adult blood decreased significantly. Fetal and cord blood contained less CD2+ and CD3+ T lymphocytes and a higher percentage of CD38 +ve cells than adult blood. The phenotypic changes occurring during perinatal age in humans relate to the changes in the functional activities of the B and T lymphoid subsets from fetal to postnatal age.

Adult↗
PubMed1993

[Vaccinations in childhood: when and why].

Community-based immunization is the primary method employed today to reduce the morbidity and mortality associated with the more common childhood viral and bacterial infections. Vaccines should be administered early in life so that the longest possible protection is offered. However the planning of vaccination programs must of course take into account the role of factors such as the immaturity of the neonatal immune system, passively acquired maternal antibodies, and the different epidemiologic and social situations. The authors discuss the epidemiology of viral and bacterial infections in infancy and the vaccination strategy to be followed for their prevention or eradication.

Bacterial Infections↗
PubMed1992

Prognostic factors and survival in children with perinatal HIV-1 infection. The Italian Register for HIV Infections in Children.

The signs that may arise after perinatal infection with human immunodeficiency virus type 1 (HIV-1) have been classified by the Centers for Disease Control, but the clinical usefulness of the classification system and the prognostic importance of each disease pattern have not been established. We sought to address these issues by analysing data from the Italian Register for HIV infection in children. We studied 1887 children born to HIV-1-seropositive mothers. 1045 were identified at birth and the others were registered later (median age 4.8 [range 0.4-72] months). HIV-1-associated signs developed in 433 (81.8%) of 529 seropositive infected children at a median age of 5 (0.03-84) months. These signs appeared significantly earlier in the 102 children who died of HIV-1-related illness than in those who are still alive (median 3 [0.03-55] vs 6 [0.03-84] months; p less than 0.001). The cumulative proportion surviving at age 9 years was 49.5% (95% confidence interval 27-65%) and the median survival time was 96.2 months. Separate analysis of the 112 seropositive infected children followed from birth and older than 15 months gave similar results. Hepatomegaly, splenomegaly, lymphadenopathy, parotitis, skin diseases, and recurrent respiratory tract infections formed the mildest disease pattern. Lymphoid interstitial pneumonitis and thrombocytopenia were signs of intermediate disease. By contrast, in multivariate analysis specific secondary infectious diseases, severe bacterial infections, progressive neurological disease, anaemia, and fever were significant and independent negative predictors of survival. Growth failure, persistent oral candidosis, hepatitis, and cardiopathy were associated in univariate analysis with significantly shorter survival. Our findings suggest that the outlook for children with perinatal HIV-1 infection is better than previously thought and that a new clinical staging system of single disease patterns is needed.

Acquired Immunodeficiency Syndrome↗
PubMed1992

T-cell receptor beta-chain gene rearrangement and expression during human thymic ontogenesis.

T-cell receptor (TCR) beta-chain proteins appear early (approximately 15th week of gestation) during human thymic ontogenesis. These beta-chain proteins, which appear before terminal deoxynucleotidyl transferase (TdT), could be an expression of a fully rearranged (V-D-J), incompletely rearranged (D-J), or germline TCR beta-chain gene. The aims of this study, performed from the 15th week onward, were the following: (1) to investigate whether or not TCR beta gene rearranges at an early stage during human thymic ontogenesis; (2) to investigate whether complete presumptive functional (1.3 kb) TCR beta gene transcript is present at these early stages of development, or if incomplete (1 kb) or germ-line (1.1 kb) transcripts are expressed; (3) to examine the phenotype of TCR beta-chain+ cells with two-color fluorescence using monoclonal antibody (MoAb) beta F1 and MoAbs that recognize CD1, CD2, CD3, CD4, CD8, CD5, and CD7 antigens (rabbit anti-calf TdT antiserum was used to detect TdT); and (4) to demonstrate whether or not beta gene N-diversity regions are detectable as early as the 15th week and whether or not N-nucleotide insertions correlate to TdT expression. Fifteen- to 22-week fetal thymuses and pediatric thymuses were investigated. We demonstrated that TCR beta-chain gene rearranged as early as the 15th week in human thymus and that a complete functional TCR beta gene transcript was expressed at these early stages of human development. No other analyses to date have investigated TCR beta gene expression in early human thymus using molecular biology techniques. No significant differences were detectable between phenotypic analysis of fetal and pediatric samples, except for TdT expression, which appeared after the 20th week. Essentially all mCD3+ (OKT3+) cells were beta-chain+ at the different weeks investigated. A significant percentage of CD1+ cells were beta-chain+, and the percentage increased along with the age of development. After the 20th week, we identified three main populations: TdT+, cCD3+, beta F-(early thymic precursors); TdT+, CD1+, beta F1+ (intermediate maturity cortical thymocytes); and TdT-, mCD3+, beta F1++ (mature medullary thymocytes). Given these values, we may consider beta-chain expression an ordered process. beta gene N-nucleotide insertions were correlated to TdT expression, since N-regions increased considerably after the 20th week. A further increase of N-nucleotide insertions was detected from the 22nd week to the 32nd week.

Age Factors↗
PubMed1992

Patterns of immunoglobulin G subclass reactivity to HIV-1 envelope peptides in children born to HIV-1-infected mothers.

OBJECTIVE: To analyse the pattern of immunoglobulin (Ig) G subclasses specific for HIV-1 envelope peptides in sera from HIV-1-infected mothers and their newborns. We sought to determine whether there was a selective transfer of antibodies from mother to child, and to establish diagnostic or prognostic properties by analysing HIV-1 peptide-specific IgG isotypes. DESIGN AND METHODS: Parallel sera from 12 HIV-1-infected mothers and their newborn children were analysed for IgG subclass responses to six HIV-1 envelope peptides by enzyme-linked immunosorbent assay. Levels of IgG were compared with levels of IgG1 and IgG3 to an immunodominant gp41 peptide in children's sera obtained during the first months of life. In a longitudinal study of 16 children born to HIV-1-seropositive mothers, of whom 11 were infected, the IgG1 and IgG3 responses to peptides representing an immunodominant epitope of gp41 and the principal neutralizing determinant of the gp120 V3 region were analysed. RESULTS: IgG1 and IgG3 were found to constitute the predominant peptide-specific antibody responses. A parallel distribution of IgG subclass reactivity was seen in maternal and paediatric sera. There was no evidence of selective antibody transfer. Comparable levels of IgG and IgG1 to the immunodominant peptide were seen in infected and uninfected children, while the IgG3 had disappeared in the majority of uninfected children. A decrease in peptide-specific IgG1 and IgG3 levels was observed in sequential sera from uninfected children, although the kinetic profile varied. Sera from infected children showed de novo synthesis of IgG1 and/or IgG3 binding to the selected HIV-1 peptides. Most children with rapid disease progression failed to produce IgG1 and/or IgG3 to the V3 peptide. CONCLUSION: Analysis of IgG subclass kinetics to selected HIV-1 peptides might be a useful additional diagnostic and prognostic tool in evaluating HIV-1 infection in children born to seropositive mothers.

Adult↗
PubMed1992

HLA-associated susceptibility to HIV-1 infection.

We studied HLA antigen distribution of 50 heterosexual partners of HIV+ drug abusers with more than 1 year of sexual exposure to HIV, 36 children born to seropositive mothers and 61 haemophiliac patients exposed to presumably infectious clotting factor concentrates. B52 and B44 antigens were associated with HIV resistance while B51 was associated with HIV susceptibility. Forty-nine HIV+ drug abusers, spouses of heterosexual partners studied and 25 HIV+ mothers of the children were also typed. DR11 phenotype was associated with infectiousness of HIV+ subjects. Our data suggest that the HLA region controls susceptibility to infection with HIV and infectiousness of HIV+ subjects in different risk groups.

Acquired Immunodeficiency Syndrome↗
PubMed1992

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↗
PubMed1992

T-cell subpopulations in pediatric healthy children: age-normal values.

Assessment of the percentage and absolute number of T cells as well as of their main subpopulations is presently a routine procedure for the diagnosis and follow-up of a wide array of pediatric immunologic disorders. For several clinical applications (severe immunodeficiencies or leukaemias) the diagnostic usefulness of their enumeration does not require close comparison with age normal values, while in other circumstances such as follow-up of immunomodulating or immunosuppressive treatments or detection of minor immune defects, the expected changes of T cell subsets are more subtile and they are likely to be detected only by comparison with well-defined age normal values. In the present study CD3, CD4 and CD8 positive cells were enumerated in a group of 410 healthy children of age ranging from 30 days to 9 years. No significant changes in percentage or absolute number were observed during infancy and childhood. Furthermore the sum of CD4 and CD8 positive cells was close to the percentage of CD3 positive cells, suggesting a phenotype maturity of T cells from infancy.

CD3 Complex↗