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Biomedical subjects

M E Rossi

Publications and source records attributed to M E Rossi.

At least 19 recordsLinked to original sources

Lack of transmission of TT virus through immunoglobulins.

BACKGROUND: A high prevalence of TT virus (TTV) infection has been found in patients who received blood or blood components. Viral DNA was demonstrated in commercial preparations of FVIII and F IX, but very few data have been reported on immunoglobulins. The risk of TTV infection associated with intramuscular or IV immunoglobulin administration is unclear. STUDY DESIGN AND METHODS: The prevalence of TTV infection in a group of patients undergoing lifelong therapy because of congenital immunodeficiency has been evaluated in a long term follow-up (median, 6 years). Seventeen patients with congenital immunodeficiency receiving monthly administration of IVIG were included in the study. TTV DNA was repeatedly evaluated by PCR in serum samples from each patient during the follow-up. Research of antibodies against TTV was not applicable, as the patients studied were unable to produce antibodies. The presence of TTV was also evaluated in 15 IVIG lots. RESULTS: The total amount of immunoglobulin administered was 18,773 g. TTV infection was not found in any patients included in the study. None of the 15 immunoglobulin preparations analyzed was found positive for TTV DNA. CONCLUSION: Despite the high prevalence of TTV in blood donors, commercial immunoglobulins are safe and unable to transmit TTV.

Adolescent↗

Inhibition of natural killer cell cytotoxicity and interferon gamma production by the envelope protein of HIV and prevention by vasoactive intestinal peptide.

Natural killer (NK) cell dysfunction is common in human immunodeficiency virus (HIV)-infected subjects, although its mechanisms are poorly understood. A direct effect of HIV envelope glycoprotein gp120 may be involved. We investigated the in vitro effects of gp120 on the major NK cell effector functions, natural cytotoxicity and cytokine production. In addition, the ability of the vasoactive intestinal peptide (VIP) to modulate these effects was investigated. Our results indicated that gp120 inhibits NK natural cytotoxicity and showed, for the first time, that the inhibition affects also the production of the proinflammatory cytokine interferon-gamma (IFN-gamma). Interestingly, the inhibitory effect on NK cell functions was obtained with gp120 at concentrations within the range measured in the serum of HIV-infected subjects. Furthermore, we showed that the inhibitory activity of gp120 can be prevented by coincubation with VIP, even if VIP has no stimulatory activity by itself. Taken together these data suggest that (1) an inhibitory effect of gp120 may account for the NK cell dysfunction in HIV-infected subjects; (2) the gp120-mediated decrease in IFN-gamma production by NK cells may contribute to the cytokine imbalance observed in HIV infection; and (3) VIP counteracts the inhibitory effect of gp120 on NK cell functions.

Cytotoxicity Tests, Immunologic↗

Interleukin-6 release by cultured peripheral blood mononuclear cells inversely correlates with height velocity, bone age, insulin-like growth factor-I, and insulin-like growth factor binding protein-3 serum levels in children with perinatal HIV-1 infection.

Spontaneous and phytohemagglutinin (PHA)-stimulated interleukin (IL)-6 release by cultured peripheral blood mononuclear cells was related to height velocity, bone age, insulin-like growth factor-I (IGF-I), and IGF binding protein-3 (IGFBP-3) serum level standard deviation scores (SDS) of 32 children [aged 91 (median; range 13-151) months] with human immunodeficiency virus-type 1 (HIV-1) perinatal infection and severe disease. Spontaneous and PHA-stimulated IL-6 release inversely correlated with height velocity, bone age, IGF-I, and IGFBP-3 SDS. Ten children with height velocity SDS </= -2, compared to 22 children with height velocity SDS > -2, showed higher spontaneous and PHA-stimulated IL-6 release and lower IGF-I and IGFBP-3 SDS (irrespective of CD4-positive T-lymphocyte counts, viral load, liver disease, or nutrition status). IL-6 overproduction may be a mechanism of IGF-I and IGFBP-3 down-regulation and impaired linear growth in children with perinatal HIV-1 infection. Growth-promoting strategies, including targeted anticytokine treatments, could be devised for such children.

Age Determination by Skeleton↗

Interleukin-6 synthesis and IgE overproduction in children with perinatal human immunodeficiency virus-type 1 infection.

BACKGROUND: Unbalanced interleukin network and elevated IL-6 synthesis are suggested mechanisms of immunoglobulin overproduction in children with perinatal human immunodeficiency virus-type 1 (HIV-1) infection. OBJECTIVE: To investigate whether elevated IL-6 synthesis is a general mechanism of immunoglobulin overproduction in perinatal HIV-1 infection. METHODS: In vitro spontaneous and phytohaemoagglutinin (PHA)-stimulated IL-6 and IL-2 synthesis, serum IgE, IgG, IgA, and IgM levels, CD4+ T-lymphocyte counts, and HIV-1 RNA copy numbers were cross-sectionally determined in 31 children with perinatal HIV-1 infection. Children with immunoglobulin z-scores in the highest quartile were defined as children with high immunoglobulin level. Relationships between interleukin synthesis, high immunoglobulin levels, and HIV-1 related disease were studied. RESULTS: Children with high IgE levels had higher spontaneous IL-6 synthesis (1337 +/- 138 pg/mL) compared with those without high IgE levels (861 +/- 194 pg/mL; P < .001). By contrast, spontaneous IL-6 synthesis was similar in children with or without high IgG, IgA, or IgM levels. Decreased PHA-stimulated IL-2 synthesis, low CD4+ lymphocyte counts, elevated HIV-1 RNA copy numbers, and severe disease correlated with high IgE (but not IgG, IgA, and IgM) levels. IgG, IgA, and IgM levels correlated with each other, but not with IgE levels. CONCLUSION: The increased IL-6 synthesis in HIV-1+ children may affect IgE rather than other immunoglobulin isotype levels. Overall results suggest that IgE and IgG, IgA, IgM overproduction have distinct underlying mechanisms.

CD4 Lymphocyte Count↗

Low IgG3 and high IgG4 subclass levels in children with advanced human immunodeficiency virus-type 1 infection and elevated IgE levels.

BACKGROUND: IgG3 and IgG4 levels are not always changed in children perinatally infected with human immunodeficiency virus-type 1 (HIV-1). Elevated IgE levels hallmark the TH1 to TH2 switch occurring in advanced infection and such an unbalanced cytokine network may affect the IgG subclass production. OBJECTIVE: To examine the different behaviour of IgG3 and IgG4 in the light of elevated IgE levels. METHODS: IgE and IgG subclass levels were cross-sectionally determined (by radioimmunoassay and enzyme-linked immunosorbent assay, respectively) in 54 HIV-1 perinatally infected children. IgE levels beyond the upper 95% confidence limits (95%CL) of the age-related reference values defined elevated IgE levels. Since immunoglobulin levels physiologically vary with age, individual z-scores of isotype levels were calculated using the upper 95%CL of age-related reference values. RESULTS: Fifteen (27.7%) children had elevated IgE levels. They had lower IgG3 (mean +/- standard deviation: -1.4+/-0.9 versus 6.9+/-0.9; P < .0001) and higher IgG4 (3.1+/-0.6 versus 0.2+/-0.3; P < .0001) z-scores compared with children without elevated IgE levels. Similar IgG1 (11.7+/-1.8 versus 12.6+/-1.3) and IgG2 (-0.22+/-0.8 versus -0.19+/-0.6) z-scores were found. In children with elevated IgE levels, IgE and IgG3 z-scores inversely correlated (r = -0.867; P < .0001), IgE and IgG4 z-scores directly correlated (r = 0.831; P < .0001) and IgG3 and IgG4 z-scores inversely correlated (r = -0.745; P < .001). CONCLUSION: Low IgG3 and high IgG4 levels may be present in HIV-1 advanced disease with elevated IgE levels. Changes may be in line with the TH1 to TH2 switch and contribute to disease progression.

CD4-Positive T-Lymphocytes↗

Viral load and CD69 molecule expression on freshly isolated and cultured mitogen-stimulated lymphocytes of children with perinatal HIV-1 infection.

HIV-1 in adults changes the proportion of mitogen-stimulated lymphocytes expressing the CD69 activation molecule, but little is known about this molecule expression on lymphocytes of HIV-1-infected (HIV-1+) children. Freshly isolated CD3+, CD4+, CD8+ and CD19+ and phytohaemagglutinin (PHA)-stimulated CD3+, CD4+ and CD8+ lymphocytes co-expressing CD69 were investigated cross-sectionally (adopting a MoAb double-staining technique) in 24 HIV-1+ children with severe disease and given anti-retroviral therapy and in 24 age-matched healthy children. CD69 results in HIV-1+ children were correlated with plasma HIV-1 RNA load prospectively determined. HIV-1+ compared with healthy children had higher frequencies of freshly isolated CD3+CD69+ (2.4 +/- 2.2% versus 0.9 +/- 0.5%; P = 0.002) and CD8+CD69+ (1.5 +/- 1.1% versus 0. 5 +/- 0.2%; P < 0.0001) lymphocytes. The frequencies of CD4+CD69+ and CD19+CD69+ lymphocytes were similar. High viral load correlated with an elevated proportion of freshly isolated CD3+CD69+ and CD8+CD69+ lymphocytes. HIV-1+ children showed reduced frequencies of PHA-stimulated CD3+CD69+ (60.7 +/- 7.6% versus 86.1 +/- 7.6%; P < 0. 001), CD4+CD69+ (73.6 +/- 18.2% versus 92.6 +/- 5.1%; P < 0.001), and CD8+CD69+ (51.0 +/- 19.1% versus 65.3 +/- 15.4%; P = 0.007) lymphocytes. Virologic worsening within 6 months correlated with a low proportion of PHA-stimulated CD3+CD69+ and CD8+CD69+ lymphocytes. CD69 molecule expression reflected the coexistence of immune activation and immune deficiency in HIV-1 infection. Changes partly differed from those observed in HIV-1+ adults. CD8+CD69+ (but not CD4+CD69+) lymphocyte proportion correlated with virologic course, and an impaired ability of CD8+ lymphocytes to express CD69 upon PHA stimulation preceded a virologic worsening.

Antigens, CD↗

Skin diseases in immigrants seen as out-patients in the Institute of Dermatology of the University of Rome 'La Sapienza' from 1989 to 1994.

In the Institute of Dermatology of the University of Rome 'La Sapienza' (IDURLS) from 1989 to 1994, 2198 immigrants from countries outside the European Community were seen as out-patients. Their personal and pathological data were collected by a particular software 'Questio', set up together with colleagues of the Interdepartimental Center for Scientific Calculous (ICSC) of the University of Rome 'La Sapienza'. The number of patients has been increasing from 326 in 1989 to 436 in 1994. Most of the people were coming from Africa, but from 1989 to 1994 the number of patients from the regions of ex-Yugoslavia has been increasing. About one third of the immigrants were unemployed, whereas 40% of them had a job (worker or employee), and the remaining 20% was composed by students and housewives. Most immigrants (1474 patients) were 20-39-year-old. Their data were compared with those of a control group composed by 2100 Italian people of the same age and sex, seen as out-patients in IDURLS in the same period. The most frequent skin disorders observed in immigrants were skin infectious or parasitic diseases, above all scabies. Excluding people with scabies, both immigrants and Italian patients shared the same skin diseases typical of young adult people: many fungal infections, many contact dermatitis and very few skin malignant tumors.

Adolescent↗

Hepatitis G virus infection in human immunodeficiency virus type 1-infected mothers and their children.

Hepatitis G virus (HGV) RNA and anti-E2 glycoprotein antibody (E2Ab) seroprevalence was studied in 58 human immunodeficiency virus type 1 (HIV-1)-infected mothers (34 injecting drug users [IDUs] and 24 with risky sexual behavior [RSB]) and their children (median age, 5 days; range, 1-27). Twelve women (20.6%) were RNA- and 20 (34.4%) E2Ab-positive. Seroprevalence was similar in the IDU and RSB groups and high in RSB partners of IDU men. Five (41.6%) children of RNA-positive mothers were HGV-infected, at a median age of 5 days (range, 1-27), independent of maternal CD4 T lymphocyte numbers, mode of delivery, and HIV-1 transmission; no other child at risk became RNA-positive subsequently. No HGV-infected child (follow-up, 16 months; range, 12-52) showed increased liver enzyme levels; 3 children cleared RNA and E2Ab-seroconverted after 10-48 months. Thus, in HIV-1-infected women, HGV infection is common and also sexually transmitted, and clearance may be impaired. Mother-to-child transmission is frequent and occurs antenatally; children remain long infected without evident disease.

AIDS-Related Opportunistic Infections↗

Different meaning of CD38 molecule expression on CD4+ and CD8+ cells of children perinatally infected with human immunodeficiency virus type 1 infection surviving longer than five years.

We investigated the relationship between CD4+CD38+, CD4+HLA-DR+, CD8+CD38+, and CD8+HLA-DR+ cell proportions (HLA-DR = major histocompatibility complex class II) (determined by two-color immunofluorescence) and the clinical condition, IL-2 and IL-6 production, viral RNA copy numbers, and the eventual immunologic-virologic course in 25 children perinatally infected with HIV-1 surviving longer than 5 y [median age, 92 (range, 63-136) mo]. Twelve healthy age-matched children were studied as control subjects. HIV-1+ children had lower percentages and absolute numbers of CD4+CD38+, whereas the percentages of CD4+HLA-DR+ and the percentages and absolute numbers of CD8+CD38+ and CD8+HLA-DR+ cells were higher than that of control subjects. The absolute numbers of CD4+ and the percentages of CD4+CD38+, CD8+CD38+, and CD8+HLA-DR+ cells directly correlated, whereas the percentages of CD4+CD38+ and CD4+HLA-DR+ cells, the percentages of CD4+CD38+ and CD8+CD38+ cells, the CD8+ cell absolute numbers, and the percentages of CD8+CD38+ cells did not. Severe manifestations and immunologic deterioration occurred in children with low CD4+CD38+ cell percentages, whereas virologic worsening was associated with low CD8+CD38+ and CD8+HLA-DR+ cell percentages. IL-2 production directly correlated with percentages and absolute numbers of CD4+CD38+ and CD8+CD38+ cells. RNA copy numbers inversely correlated with CD4+CD38+, CD4+HLA-DR+, CD8+CD38+, and CD8+HLA-DR+ cell percentages. This suggests that CD38 molecule expression on both CD4+ and CD8+ cell subsets is a favorable marker in HIV-1+ children. Perhaps CD8+CD38+ subsets are activated cells, whereas CD4+CD38+ subsets are immature cells, possibly the host's attempt at CD4+ cell renewal.

ADP-ribosyl Cyclase↗

Acellular pertussis vaccine in children with perinatal human immunodeficiency virus-type 1 infection.

The immunogenicity of an acellular pertussis vaccine containing genetically detoxified pertussis toxin, filamentous haemoagglutinin and pertactin was studied in 12 children [median age: 45 (6-107) months] with perinatal human immunodeficiency virus-type 1 (HIV-1) infection. Antibody response to all antigens was observed in six cases and another children 3 reacted to two or one antigen(s), but titres were lower than those from healthy controls. Antibody titre fold-rise correlated with preimmunization CD4-positive cell counts. Significant titres were still detectable 4 months after the third dose. The acellular vaccine is immunogenic in a portion of children with perinatal HIV-1 infection but early vaccination might be more effective, taking advantage of still adequate CD4-positive cell numbers.

Acquired Immunodeficiency Syndrome↗

Does the classification system fit disease progression in perinatal human immunodeficiency virus infection?

The objective was to test the applicability of the new classification for paediatric human immonodeficiency virus infection. The person-time of each state, transition probabilities and survival (+/- standard errors) at 5 years, and median sojourn-time were calculated on 39 perinatally infected children followed up from the first month of life for a median of 64.5 (1.2-120.1) months. The person-times of the N2, N3, B1, C1, and C2 states were low. The transition probabilities and sojourn-times were similar for A (48.1 +/- 10.8%; 63.5 months), B (50.5 +/- 15.5%; 44.9 months) and C (74.6 +/- 15.1%; 43.1 months) clinical categories, which differed (p < 0.025) from the N category (87.9 +/- 5.5%; 12.05 months). The survival probabilities after 5 years of entering the A, B and C categories were 84.8 +/- 10.7%, 60.5 +/- 19.8% and 14.8 +/- 13.5%, respectively (p < 0.001). Immunological category 3 had lower transition probabilities and longer sojourn-times (58.8 +/- 16.6%; 53.3 months) than categories 1 (71.3 +/- 8.1%; 33.2 months) and 2 (75.6 +/- 10.5%; 19.8 months) (p < 0.01). The transition probabilities to C3 for states N3, A3 or B3 were 52.5 +/- 13.5%. In conclusion, the classification fits the clinical history better than the immunological history.

Age Factors↗

Mother-to-infant transmission of hepatitis C virus.

Anti-hepatitis C virus (HCV) antibodies and HCV-RNA were measured in the sera of 22 anti-HCV positive, HIV-1 negative mothers and their infants. ELISA and RIBA II were used for anti-HCV determination. HCV-RNA was measured by a nested polymerase chain reaction. HCV-RNA was found in 12 of 22 mothers. All 22 children were followed for 12 months. All were anti-HCV positive by the fourth month; 18 became anti-HCV negative between the 8th and 12th month. HCV-RNA was detected in 5 of 22 infants in the fourth month. They remained HCV-RNA positive. All children born to HCV-RNA negative mothers were HCV-RNA negative while 5 of 12 babies born to HCV-RNA positive mothers were infected. All five infected babies were born to mothers infected through transfusions or drug use. ALT levels in mothers seemed to have no effect on mother-to-infant transmission. Hence evidence for perinatal transmission of HCV from HCV-RNA positive mothers was demonstrated in the present study.

Adult↗