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Biomedical subjects

I Quinti

Publications and source records attributed to I Quinti.

At least 37 records · Page 2Linked to original sources
PubMed1995

Response to hepatitis B vaccine in a cohort of Gambian children.

In a cohort of 1000 Gambian children immunized with four doses of 10 micrograms of plasma-derived hepatitis B virus vaccine, 44 subjects (4.4%) showed no response (< 10 mIU/ml; 6 subjects) or low specific antibody response (10 to 99 mIU/ml; 38 subjects) to hepatitis B surface antigen. Serologic indices, potentially correlated with low immunologic response, were investigated in sera obtained from these children and in sex-, age- and village-matched controls who showed a normal response. The presence of circulating immune complexes in similar proportion of responding and poorly responding children together with a low prevalence of rheumatoid factors suggested that polyclonal B cell activation was not correlated with the subnormal humoral response. Concentrations of serum immunoglobulin (Ig) and IgG subclasses did not differ in the two groups. Some of the African prevalent Ig allotypes were determined, but no significant differences in the two groups were found. The humoral response to hepatitis B surface antigen did not correlate with the response to tetanus toxoid.

Antigen-Antibody Complex↗
PubMed1995

HCV infection in patients with primary defects of immunoglobulin production.

We tested for infection with hepatitis C virus (HCV) in 58 patients affected by humoral immunodeficiencies: 43 common variable immunodeficiency (CVI), two hyper IgM syndrome (HIM), two IgG subclass deficiency, four ataxia-telangiectasia (AT), and seven X-linked agammaglobulinaemia (XLA). While the assessment of serum specific HCV antibodies in some of these patients was not informative because of the impairment in specific antibody production, the reverse transcriptase polymerase chain reaction (RT-PCR) assay used to detect serum HCV RNA was a useful method for diagnosing infection. We found that 38% of late onset hypogammaglobulinaemic patients (CVI, HIM or IgG subclass deficiency) had evidence of HCV infection. HCV infection was not detectable in patients with XLA or AT. The majority of our patients had persistent viraemia, and those who underwent liver biopsy showed histological findings of chronic hepatitis. Moreover, we could demonstrate in vitro that eight of 18 HCV-infected patients were actively producing anti-HCV antibodies, despite their impaired antibody production. The high rate of HCV infection in hypogammaglobulinaemic patients could be related to several nosocomial routes of transmission, including intravenous immune globulin administration. Despite the persistent viremia only two patients had cirrhosis and none had hepatocarcinoma.

Adolescent↗
PubMed1994

Humoral immunity in aging.

The interactions between B and T lymphocytes, leading to the development of humoral responses, are reviewed with references to the changes occurring in aged people. Aging is perceived as a process of impairment of immune functions; it is known that T cells from aged subjects have a reduced ability to produce IL-2. However, other functions seem to be upregulated in elderly subjects; indeed, IL-1, IL-3, IL-4, IL-6 and TNF alpha production are increased both in aged mice and humans. These cytokines are known to control B cell differentiation, through isotype switch and Ig production. A significant increase in IgG subclasses and IgA is observed in sera of aged subjects. This contrasts with the significant decrease in circulating B lymphocytes. The impairment of primary responses to immunization, and other aspects of humoral immunity, including mucosal responses, autoantibody production and correlations with phenotypic markers of T and B cell subsets, are discussed.

Adult↗
PubMed1994

Hepatitis C virus transmission by intravenous immunoglobulin.

The polymerase chain reaction was used to detect hepatitis C virus infection in patients who had previously been reported to have developed non-A, non-B hepatitis after intravenous immunoglobulin infusion. Of the 33 patients with intravenous immunoglobulin associated non-A, non-B hepatitis studied, HCV RNA could be detected in 15 out of 17 patients (88%) who were HCV RNA negative prior to the development of non-A, non-B hepatitis after implicated intravenous immunoglobulin batches. Similarly, eight out of nine patients (89%) in whom no sample was available for polymerase chain reaction testing prior to intravenous immunoglobulin therapy, had detectable HCV RNA after intravenous immunoglobulin therapy with intravenous immunoglobulin batches implicated in non-A, non-B hepatitis transmission. Two of the three intravenous immunoglobulin preparations implicated in non-A, non-B hepatitis transmissions that were available for polymerase chain reaction testing also had detectable HCV RNA, confirming that hepatitis C virus is the implicated virus in intravenous immunoglobulin-associated non-A, non-B hepatitis.

Hepacivirus↗
PubMed1993

Mannoprotein-induced anti-U937 cell cytotoxicity in peripheral blood mononuclear cells from uninfected or HIV-infected subjects: role of interferon-gamma and tumor necrosis factor-alpha.

A mannoprotein fraction (MP-F2: mannan, > 90%; protein, 4.5%) from the human commensal microorganism Candida albicans was as efficient as interleukin-2 (IL-2) in generating cytotoxicity against the uninfected or human immunodeficiency virus type-1 (HIV-1) persistently infected monocytoid U937 cell line in cultured peripheral blood mononuclear cells (PBMC) from healthy human subjects. MP-F2-activated killing of U937 cells (U937-MAK) decreased progressively with advancing stages of HIV-1 infection to virtually no killing effect in PBMC from advanced AIDS subjects (AIDS PBMC). This decrease paralleled a lowered susceptibility of U937 cells to natural killer cell activity. In contrast, IL-2-activated killing of U937 cells (U937-LAK) was not affected by the progression of HIV infection and persisted at high levels in AIDS PBMC. To shed light on the mechanisms of U937-MAK and its decrease during HIV infection, IL-1 beta, IL-6, TNF-alpha, GM-CSF, and IFN-gamma production was analyzed. Decreases in TNF-alpha, GM-CSF, and IFN-gamma, but not IL-1 beta or IL-6, levels were observed in MP-F2-stimulated PBMC from HIV-infected subjects, compared to healthy controls. Interestingly, these cytokine levels fell before the onset of AIDS. The greatest relative drop was that of IFN-gamma, from 4600 (+/- 600) to 290 (+/- 160) and 217 (+/- 110) mean pg/ml (+/- SE) in PBMC from healthy donors (11 subjects), CDC stages II + III (14 subjects), and CDC stage IV (10 subjects), respectively. The following observations suggest that decreased IFN-gamma production plays a role in the abrogation of U937-MAK activity: (i) addition of neutralizing anti-IFN-gamma antibodies abolished both IFN-gamma and U937-MAK activity in PBMC from healthy subjects; (ii) substantial levels of IFN-gamma were detected in supernatants of PBMC cultures stimulated by IL-2, in line with preserved U937-LAK activity. Interestingly, anti-IFN-gamma antibodies also abolished TNF-alpha production, and the anti-TNF-alpha antiserum effect was comparable to that of anti-IFN-gamma in U937-MAK inhibition. In contrast, anti-TNF-alpha antibodies abrogated TNF-alpha activity, but only partially reduced IFN-gamma production. Thus, in human PBMC, U937-MAK activity progressively decreases with advancing stages of HIV infection, whereas U937-LAK activity is sustained. Furthermore, the present results indicate a pivotal role for IFN-gamma in U937 MAK activity, possibly through activation of TNF-alpha production.

Adult↗
PubMed1993

Increased IL-6 gene expression and production in patients with common variable immunodeficiency.

We have studied IL-6 gene expression and production by in vitro stimulated peripheral blood mononuclear cells (PBMC) isolated from common variable immunodeficiency (CVI) patients. A strong hybridization signal for the IL-6 probe was observed in mRNA extracted from phytohaemagglutinin (PHA)- and PHA/phorbol myristate acetate (PMA)-stimulated PBMC from most of 12 CVI patients analysed. IL-6 production by PHA-stimulated PBMC from 28 CVI patients was evaluated in ELISA and found to be significantly (P < 0.0001) higher than in normal controls. IL-6 production, however, did not correlate with the lymphocyte populations examined, nor with the absolute number of monocytes. We have also showed that IL-6 was able to increase IgM secretion by several Epstein-Barr virus (EBV)-transformed cell lines derived from both normal donors and CVI patients, but it failed to modify substantially the amounts of IgM and IgG produced in vitro by PBMC derived from CVI patients and activated with pokeweed mitogen (PWM) or anti-IgM. Our data indicate that IL-6 gene expression and production is increased in CVI, but CVI cells do not respond to IL-6 with increased production of immunoglobulin.

Adolescent↗
PubMed1993

Anticandidal activity and interleukin-1 beta and interleukin-6 production by polymorphonuclear leukocytes are preserved in subjects with AIDS.

Polymorphonuclear granulocytes (PMN; or neutrophils) from uninfected or human immunodeficiency virus-infected subjects were tested for their ability to inhibit growth of Candida albicans and produce interleukin-1 beta (IL-1 beta) and IL-6 in vitro. It was seen that PMN from AIDS (Centers for Disease Control stage IV) patients expressed equal if not greater anticandidal activity compared with the activity expressed by neutrophils from all other subjects examined. On exposure to granulocyte macrophage-colony-stimulating factor or to a mannoprotein constituent (MP-F2) from C. albicans itself, PMN from AIDS patients showed enhanced antifungal activity and production of remarkable quantities of IL-1 beta and IL-6. These findings suggest that the functional abilities of PMN to inhibit Candida growth and secrete relevant proinflammatory and immunomodulatory cytokines are intrinsically preserved in AIDS patients.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Abnormalities of lymphocyte subpopulations in CVI do not correlate with increased production of IL-6.

We have determined the percentages and absolute numbers of lymphocyte subpopulations in 49 patients with common variable immunodeficiency (CVI). In vitro production of IL-6 by PHA-stimulated PBMC of 28 patients was also evaluated. Our data indicate profound alterations in the lymphocyte subpopulations evaluated, including increased CD8 cells (these cells outnumbered CD4 cells in 26 cases), severe defect of CD4 cells (< 400/mm3) in 10 cases and reduction of CD19 cells (< 50/mm3) in 11/41 cases. Increased production in vitro of IL-6 by PBMC of CVI patients does not correlate with the absolute numbers of lymphocytes, lymphocyte subpopulations, or monocytes. In addition, IL-6 was unable to significantly modify the amount of PWM-driven IgM production by CVI cells.

Adolescent↗
PubMed1992

The secretion of aspartyl proteinase, a virulence enzyme, by isolates of Candida albicans from the oral cavity of HIV-infected subjects.

Prevalence, serotype and in vitro secretion of aspartyl proteinase, a virulence enzyme, were studied in Candida isolates from the oral cavity of 337 HIV-infected subjects. Controls were 95 age-sex-matched HIV- (seronegative) subjects, belonging to either HIV-risk categories (47) or to the normal, general population (48). Fungi were isolated from 155 HIV+ subjects. C. albicans was the most prevalent species (85.8% of all isolates). 94.6% of C. albicans isolates were serotype A and all were agglutinated by a monoclonal antibody (AF1) directed against a major mannoprotein immunogen of the candidal cell wall, confirming previous results with C. albicans isolates from non-immunodeficient subjects. With regard to the stage of HIV infection, there were no statistically significant differences in the incidence of oral Candida carriage between asymptomatic (stage II) HIV+ and HIV- subjects, and between stage II and lymphadenopathic (stage III) individuals. Also, the low (3.8%) incidence of oral candidiasis in the subjects of the latter stage was insignificant with respect to stage II subjects. However, the incidence of C. albicans in stage IV (AIDS) subjects (46.8%) was significantly higher than in all other subjects, and in almost all cases, fungal isolation was accompanied by oral thrush and lower CD4+ lymphocyte counts (less than 400 x 10(6)/L). All isolates of C. albicans were proteolytic in vitro, as assessed by scoring the proteinase activity on BSA agar and monitoring the secreted proteinase antigen by a highly sensitive (1 ng) and specific immunoenzymatic assay.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1992

Human T-helper clones induce IgG production in a subclass-specific fashion.

The mechanisms governing the induction of IgG subclasses by T-helper cells in humans were investigated. As preliminary bulk-culture experiments had indicated that a direct B cell contact with viable T cells was an essential requirement for optimal IgG subclass production, 256 CD4+ human T cell clones were preactivated with PHA and cultured in direct contact with autologous B cells. These clones induced IgG production in a strikingly subclass-specific fashion. Moreover, the distribution of subclass-specific helper clones was very similar to the IgG subclass profile observed in serum and peripheral lymphoid tissue plasma cells (IgG1 approximately 60%, IgG2 approximately 30%, IgG3 approximately 5-10%, IgG4 less than or equal to 5%) and unlike that observed in resting B cells (which is IgG1 approximately 40% and IgG2 approximately 50%). It would, therefore, seem that a predominance of T cells capable of delivering IgG1-specific, as opposed to IgG2-specific, help is an essential factor for the preferential induction of IgG1 antibodies during B cell proliferation and differentiation. There was no relationship between IL2, IL4, IL6, and IFN-gamma secreted by the T-helper clones and their IgG subclass induction patterns. In addition, only a few supernatants were able to reproduce the helper effects of the clones themselves. Therefore, direct contact of B cells with helper clones is crucial for IgG-subclass production in humans.

B-Lymphocytes↗
PubMed1992

Antibody production in infants born to HIV-1-infected mothers.

Naturally occurring antibodies to polysaccharide antigens of pathogens commonly isolated from HIV-1-infected subjects were analyzed in serially collected sera of children born to seropositive mothers. Purified polysaccharides from type 14 Streptococcus pneumoniae, group C Neisseria meningitidis, type b Haemophilus influenzae, glucomannoprotein from Candida albicans and diphtheria toxoid antigens were used in an ELISA test to assess antibody levels. A significant rise of anti-pneumococcus antibody titres was noticed both in HIV-1-infected and in non-HIV-1-infected children aged 18 months or more. Anti-C. albicans and anti-group C N. meningitidis antibodies were elevated only in HIV-1-infected children older than 12 months. Anti-type b H. influenzae antibodies remained at low titres in both groups. Anti-diphtheria toxoid antibodies, analyzed as a model of humoral response to a protein antigen, were similar in both groups of HIV-1-infected and noninfected children.

Antibodies, Bacterial↗
PubMed1992

Changes in circulating B cells and immunoglobulin classes and subclasses in a healthy aged population.

The study of 87 adults of different ages, including 15 centenarians, selected for their healthy status, showed that profound changes of humoral immunity occur throughout life. In particular, a statistically significant age-related increase of the serum level of immunoglobulin classes (IgG and IgA but not IgM) and IgG subclasses (IgG1, 2 and 3, but not IgG4) was detected. A parallel age-related decrease of circulating B cells was also observed. The hypothesis of a complex derangement of B cell function and/or compartmentalization with age is put forward, together with the proposal that healthy centenarians (as representative of successful ageing) may be helpful in identifying the physiological age-related modifications of the immune system.

Adult↗
PubMed1991

Clonotypic analysis of human antibodies specific for Neisseria meningitidis polysaccharides A and C in adults.

Serum antibodies to the capsular polysaccharides A and C (PSA and PSC) of N. meningitidis in healthy adults before and after vaccination with the sole polysaccharides were analysed by isoelectric focusing (IEF). Before vaccination, 49% and 28% had naturally acquired antibodies against PSA and PSC, respectively, whereas 18 days after vaccine administration 84% and 91%, respectively, showed a detectable spectrotypic pattern. Oligoclonality appeared to be the main feature of naturally acquired and vaccine-induced antibodies for both polysaccharides. In all subjects the anti-PSA response, showing dominant bands at the same pH position, was more homogeneous than anti-PSC one. Most subjects with naturally acquired antibodies (25 out of 38 for PSA and 20 out of 22 for PSC) showed a spectrotypic pattern after vaccination, similar to that observed before vaccination (any differences were just related to band intensity), suggesting that PSA and PSC are able to recruit the same B cell clones previously primed with a T-dependent form of the antigen, i.e. the whole bacterium. However, in one-third of subjects with naturally acquired anti-PSA antibodies, the appearance of new alkaline bands after vaccination was observed. Furthermore, in subjects with absence of detectable natural antibodies, the vaccine-induced antibody response started in correspondence of alkaline pH areas, subsequently extending to neutral and acidic areas. Therefore, it may be hypothesized that alkaline antibody-secreting B cell clones are the first to be recruited. The final spectrotype in these subjects was similar to that observed in subjects with naturally acquired antibodies. This observation, together with the above reported data, allow us to conclude that natural (T-dependent pathway) and vaccine (T-independent pathway) immunization induce the expression of the same antibody repertoire, for both meningococcal PSA and PSC.

Adolescent↗
PubMed1991

Proliferative and cytotoxic responses to mannoproteins of Candida albicans by peripheral blood lymphocytes of HIV-infected subjects.

Mucosal candidiasis is one of the first opportunistic diseases in HIV-infected subjects. In order to understand the relationship between this disease and immunodeficiency to chemically defined, immunodominant Candida antigens, a mannoprotein fraction from C. albicans cell wall (GMP) was used to analyse proliferative and non-MHC-restricted cytotoxic responses of peripheral blood mononuclear cells (PBMC) from normal and HIV-infected subjects. In the former, GMP induced extensive blastogenesis, generation of powerful cytotoxicity against a tumour cell line (K562), and production of substantial amounts of interferon-gamma (IFN-gamma). Cultured PBMC from HIV-infected subjects manifested an early decreased ability for proliferative as well as differentiative cytotoxic responses to the candidal mannoproteins. This inability became clearly evident in subjects with stage III (CDC) of the disease, was total in CDC stage IV and occurred even in some subjects with a normal number of CD4+ cells. Low or absent response to GMP correlated with lack of response to tetanus toxoid. In contrast, both lymphoproliferative and cytotoxic responses to exogenous IL-2 was highly preserved at all stages of infection. The production of IFN-gamma in GMP-stimulated PBMC cultures critically fell to negligible values in most of the subjects in CDC stages II and III. Thus, the lowered or absent cell-mediated immune responses to candidal mannoprotein may be one factor to explain the early, elevated susceptibility of HIV-infected subjects to mucosal candidiasis. This study also shows that our mannoprotein preparation may be used as a probe to detect the overall efficiency of T cell responses in the above subjects.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Antibacterial polysaccharide antibody deficiency after allogeneic bone marrow transplantation.

Allogeneic bone marrow-engrafted adults immunized with meningococcal types A and C and pneumococcal type 14 polysaccharide antigens showed only low antibody titers of the IgM class, no antibody titers of the IgG or IgA classes, and no bactericidal activity in vitro. The analytical isoelectrofocusing showed the appearance of a restricted pattern of clonotypes in a minority of subjects. These observations are consistent with the hypothesis that B cells in bone marrow transplant patients express some characteristics of neonatal B cells and suggest that polysaccharide-protein conjugates, rather than isolated polysaccharide, might be utilized in the setting of bone marrow transplantation.

Adult↗
PubMed1990

Antibodies mediating cellular cytotoxicity and neutralization correlate with a better clinical stage in children born to human immunodeficiency virus-infected mothers.

In children born to human immunodeficiency virus (HIV)-infected mothers, factors that determine disease outcome and progression are unclear. Also, early diagnosis is hampered by maternally transferred antibodies. Children aged 0-24 months were retrospectively divided into two groups based on HIV seroreactivity or nonreactivity at age 15 months and analyzed for the presence of antibodies that mediate cellular cytotoxicity (ADCC) and virus neutralization. No difference was seen in the presence of these functional antibodies between groups. The persistently seropositive group was further divided into non-AIDS and AIDS groups according to clinical status at serum collection. The ADCC antibody frequencies were much higher (70%) in the non-AIDS group than in the AIDS group (30%). Of the non-AIDS children, 63% had neutralizing antibodies; no children with AIDS had these antibodies. HIV-specific ADCC and neutralizing antibodies do not seem to protect against transmission of HIV from mother to child but are significantly correlated with a better clinical stage of childhood HIV infection.

Acquired Immunodeficiency Syndrome↗