Tiina Moore

Antibody responses to bacterial toxoids in children infected with human immunodeficiency virus

Infection with human immunodeficiency retrovirus (also known as HTLV III, LAV,. and ARV) can produce a spectrum of immunologic perturbations ranging from no obvious deficit to severe combined acquired immune deficiency. Adults with acquired immune deficiency syndrome are likely to have lymphopenia and severe cell-mediated immunodeficiency, with a dramatic deficiency of helper T cells. Adults also have hypergammaglobulinemia and diminished capacity to produce antibody after primary or booster immunizations? Even asymptomatic HIV-infected adults have defective B-lymphocyte function as measured by a variety of in vitro assays. 2 In chiidren, HIV infection produces a similar spectrum of immunologic perturbations. A recent study of sick children with AIDS has demonstrated blunted antibody responses to bacteriophage phi X174 after prinmry and secondary immunizations. In addition, class switching (IgM to IgG) was generally absent and antibody responses to pneumococcal vaccine and tetanus toxoid were also diminished? We examined 17 children with HIV infection, who had received at least three immunizations with diphtheriatetanus-pertussis vaccine, for the presence of humoral and ceil-mediated immune responses to diphtheria and tetanus toxoids. These children had neither, a history of opportunistic infection nor biopsy-proved lymphocytic interstitial proliferation at the time of study. METHODS

Human-immunodeficiency-virus infections in infants negative for anti-HIV by enzyme-linked immunoassay.

Of 85 children with human-immuno-deficiency-virus (HIV) infection based on clinical (opportunistic infection), epidemiological (mother a drug addict or known to be HIV infected), and immunological (helper-T-cell deficiency and impaired proliferative response to pokeweed mitogen) features, 9 were found to lack antibody to HIV as measured by a commercial enzyme-linked immunoassay (ELISA). All 9 children had detectable levels of HIV antigen in simultaneous plasma specimens, measured by a sensitive antigen-capture ELISA. The use of the western blot assay and an ELISA with recombinant HIV antigens was able to identify HIV infection in 4 of the 9 children.

Correlation of perinatal transmission of human immunodeficiency virus type 1 with maternal viremia and lymphocyte phenotypes

OBJECTIVE To determine whether maternal transmission of human immunodeficiency virus (HIV) is correlated with increased quantities of HIV, decreased frequencies of CD4+ T cells, or increased levels of CD8+ T cells in the transmitting mother. METHODS Peripheral blood obtained from HIV-infected women at different times during pregnancy was used to measure quantitative cell-associated HIV-1 and CD3+CD4+ and CD3+CD8+ proportions; the plasma was used to perform measurements of quantitative viremia by culture and subsequently to measure quantitative HIV-1 ribonucleic acid levels. These measurements were analyzed with respect to their association with HIV transmission to the baby, which occurred in one fourth of the cases. The children were also studied to determine whether HIV-1 was detected near birth or not until 1 to 8 weeks of life. RESULTS Increased clonal frequencies of HIV-1-infected peripheral blood mononuclear cells were found in mothers of infected children; fivefold fewer cells were required for a positive culture result (median cell numbers of 10(4.5) vs 10(5.2); p = 0.008). Higher frequencies of infected cells were seen in mothers of babies with evidence of infection at birth than in mothers of infected babies without evidence of infection at birth (p < 0.05). Plasma viremia was measured in 10% of cultures without regard to whether the mothers transmitted virus to their babies. Increased levels of ribonucleic acid as detected by the branched-chain DNA method were measurable more often (45% vs 17%) in the mothers of infected children than in mothers of uninfected children. Proportions of CD4+ and CD8+ T cells were indistinguishable in these two groups of women. CONCLUSIONS Increased viremia was present in mothers who transmitted HIV to their offspring. This variable could be used to select women at highest risk of transmitting HIV to their offspring for treatment to decrease the HIV burden five-fold.

Cell-mediated and humoral immune responses in children infected with human immunodeficiency virus during the first four years of life

OBJECTIVES To determine whether cell-mediated and humoral immune responses to recall antigens develop in children infected with the human immunodeficiency virus (HIV) and, if so, whether these responses are retained. METHODS Children infected with HIV and uninfected children born to mothers infected with HIV were compared with respect to lymphoproliferative responses to recall antigens and protective levels of antibody to bacterial toxoids during the first 4 years of life. RESULTS Children infected with HIV who were enrolled in a prospective study of the natural history of the infection were relatively normal (1) in their lymphoproliferative responses to diphtheria toxoid, tetanus toxoid, and Candida, and (2) in their ability to make protective diphtheria and tetanus antitoxins during the first 2 years of life. During the next 2 years, attrition was noted in both lymphoproliferative and humoral responses. Attrition in response was not necessarily correlated with declining numbers of helper T cells. CONCLUSIONS These results suggest that both cellular and humoral immune responses develop early in life in most children infected with HIV, while they remain relatively well both clinically and immunologically. Previously reported severe immune deficits in these children were probably attributable to advanced clinical disease when they were first studied.

Human immunodeficiency virus type 1 antigenemia in children

Human immunodeficiency virus type 1 (HIV-1) core antigen was assayed in the plasma of children at risk for infection with HIV to determine its usefulness in the diagnosis of infection and to correlate it with the clinical stage of disease. Antigen was detected in the plasma of all children less than 15 months of age with acquired immunodeficiency syndrome (AIDS). Two thirds of children with AIDS-related illnesses and half of children with asymptomatic infection had antigen. Although 53% of plasma specimens originating from HIV-infected children younger than 6 months of age contained antigen, only 25% of plasma specimens from children younger than 6 months who had no symptoms and none of the 10 specimens from HIV-infected newborn infants contained antigen. Half of the specimens containing core antigen also contained anticore antibody. Quantitative mean antigen levels were more likely to be elevated in children with AIDS (516 pg/ml) than in children with AIDS-related illnesses (295 pg/ml) or in those who had no symptoms (70 pg/ml). Antigen levels tended to increase over time in children with advancing clinical illness, but they tended to decrease over time after a diagnosis of AIDS was made. Antigen was detected in the plasma of 4 of 14 children without symptoms who subsequently reverted to an HIV seronegative state. We conclude that the detection of core antigen occurs with high frequency in children, even young infants, with symptomatic HIV infection. Plasma core antigen was less frequent in children without symptoms and was not detected in 10 infected children when they were tested at birth.

Evolution of phenotypic memory T cells in HIV-1 infected infants and children☆

Infants are reported to be devoid of memory T cells at birth but acquired them with time. A cross-sectional study of peripheral blood mononuclear cells from HIV-infected and uninfected infants and children that bear the CD4R0 antigen was undertaken to describe the development of memory T cells. Linear regression lines derived from the data revealed increasing percentages of memory CD4 and CD8 cells in the uninfected children. Memory CD4 cells in the infected children were detected at a frequency equal to or greater than that seen in uninfected children until 6 months of age but subsequently declined with age. In contrast, memory CD8 cells were found to be significantly increased in HIV-infected children early in life with a rate of increase similar to that seen in the uninfected population. This increase in memory CD8 cells may facilitate the early diagnosis of HIV infection.

Lack of predictive value of maternal human immunodeficiency virus p24 antigen for transmission of infection to their children

The association of maternal-to-infant transmission of human immunodeficiency virus type 1 (HIV-1) with maternal p24 antigenemia was assessed in 86 HIV-1-infected mothers. We retrospectively examined serum or plasma samples collected in the peripartum period (delivery +/- 11 days; sd 16.89 days; range, delivery +/- 2 months). Immune complexes of p24 antigen and anti-p24 antibody were dissociated using acid hydrolysis (Method A, glycine-HCl buffer; Method B, HCl) in an attempt to increase the sensitivity of the test. The detection of HIV-1 p24 antigenemia in serum was increased from 23 of 86 (26.7%) to 37 of 82 (45.1%) following acid hydrolysis with Method A (chi square = 5.4, P = 0.02) and to 36 of 78 (46.1%) with Method B (chi square = 5.874, P = 0.015). Mothers of HIV-1-infected children were no more likely to have p24 antigenemia than mothers of seroreverted infants when untreated samples were assayed (7 of 23 vs. 10 of 48; chi square = 0.348, P = 0.55). Although acid hydrolysis increased the ability to detect p24 antigen, it did not enhance any association between p24 antigenemia and maternal-to-infant transmission of HIV infection: Method A, 9 of 23 in mothers of infected children vs. 21 of 45 in mothers of seroreverted children (chi square = 0.112, P = 0.738); and Method B, 9 of 22 in mothers of infected children vs. 18 of 42 in mothers of seroreverted children (chi square = 0.014; P = 0.907), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

RETROVIRAL ANTIGENEMIA IN CHILDREN WITH HIV INFECTION

A selected group of 16 children with suspected or documented infection with the Human Immunodeficiency Virus (HIV) were tested for HIV antigen using an ELISA antigen capture assay. Fifteen were antigen positive at some time in their life. Two of these 15 children had immunologic abnormalities but were consistently HIV antibody negative (HIV Ab−). Five of the children were tested during the neonatal period and subsequently for 4-10 months. All 5 are HIV Ab+ but immunologically and clinically well to date. Three of the 5 were HIV antigen negative (HIV Ag−) at birth but 2 have since become HIV antigen positive (HIV Ag+). Two of the 5 were HIV Ag+ at birth but one is HIV Ag− after 8 months. Two HIV Ab+ Ag− mothers produced children who were HIV Ag+ at birth. Two HIV Ab+ Ag+ mothers produced children who were HIV Ag− at birth. Thus HIV antigen need not passively cross the placenta as does HIV antibody. Two sets of HIV Ab+ twins were also HIV Ag+. One of each set of twins developed severe HIV-related illness in the 1st 4 months of life. Within each set, the affected twin had the higher titre of antigen. Measurement of HIV antigen may be useful in evaluating the presence of HIV infection in the first months of life, irrespective of their HIV antibody status, particularly when repeated at regular intervals.