Natasha L. Martin

Detection of infection with human immunodeficiency virus (HIV) type 1 in infants by an anti-HIV immunoglobulin A assay using recombinant proteins

To diagnose infection with the human immunodeficiency virus (HIV) soon after birth in infants born to HIV type 1-infected women, we developed antiviral IgA Western blot and dot blot assays with recombinant HIV-1 proteins. Thirty-three infants born to HIV-1-seropositive mothers and nine infants born to HIV-1-seronegative intravenous drug-abusing mothers were followed prospectively. Infection was documented by positive virus culture. Results with the polymerase chain reaction were used for comparison. Twelve infants were found infected with HIV-1; the earliest age at which cultures became positive ranged from birth to 31 weeks of age. Of the 12 culture-positive infants, 10 had anti-HIV IgA antibodies detectable initially between birth (cord blood) and 27 weeks of age. Anti-HIV IgA was not present in the uninfected infants or in the control subjects, either by Western blot or dot blot assays. Testing for anti-HIV IgA antibodies with recombinant HIV-1 proteins is an effective method for detecting viral infection in newborn and young infants.

Immunologic changes occurring at kindergarten entry predict respiratory illnesses after the Loma Prieta earthquake.

Previous studies in adult populations have demonstrated alterations in immune function after psychologically stressful events, and pediatric research has shown significant associations between stress and various childhood morbidities. However, no previous work has examined stress-related immune changes in children and subsequent illness experience. Twenty children were enrolled in a study on immunologic changes after kindergarten entry and their prospective relationship to respiratory illness (Rl) experience. Midway through a 12-week Rl data collection period, the October 17, 1989 Loma Prieta earthquake occurred. The timing of this event created a natural experiment enabling us to study possible associations between immunologic changes at kindergarten entry, the intensity of earthquake-related stress for children and parents, and changes in Rl incidence over the 6 weeks after the earthquake. Immunologic changes were measured using helper (CD4+)-suppressor (CD8+) cell ratios, lymphocyte responses to pokeweed mitogen, and type-specific antibody responses to Pneumovax, in blood sampled 1 week before and 1 week after school entry. Rl incidence was assessed using home health diaries and telephone interviews completed every 2 weeks. Rls per child varied from none to six. Six children showed an increase in Rl incidence after the earthquake; five experienced a decline. Changes in helper-suppressor cell ratios and pokeweed mitogen response predicted changes in Rl incidence in the postearthquake period (r = .43, .46; p < .05). Children showing upregulation of immune parameters at school entry sustained a significant increase in Rl incidence after the earthquake. These findings suggest that individual differences in immune reactivity to a minor normative stressor may be related to the rate of infection after a major stressful event. J Dev Behav Pediatr 14:296–303, 1993. Index terms: stress, respiratory infection, psychoneuroimmunology.

Safety and Immunogenicity of HIV Recombinant Envelope Vaccines in HIV-Infected Infants and Children

Study objectives were to evaluate the safety and immunogenicity of three HIV recombinant glycoproteins in HIV-infected infants and children between 1 month and 18 years of age with asymptomatic (P-1) infection. Using Chiron rgp 120 (SF-2) 15 or 50 microg; MicroGeneSys rgp 160 (IIIB) 40 or 320 microg; Genentech rgp120 (MN) 75 or 300 microg; or adjuvant control (Alum or MF-59), children were randomized to a double-blind, placebo-controlled, dose-escalating study of vaccine administered intramuscularly at entry and 1, 2, 3, 4, and 6 months later. No adverse events were attributed to study vaccines. Between 30% and 56% of volunteers exhibited a lymphoproliferative response as defined in terms of stimulation index (SI) to vaccine antigens; 65% of vaccinees but none of placebo recipients exhibited moderate or strong responses after enzyme immunoassay to HIV specific antigens. CD4 cell counts and quantitative HIV culture did not differ significantly among vaccine and control groups, nor were differences found among groups in HIV disease progression. The rgp160 and gp120 subunit vaccines were safe and immunogenic in this population.

Low number of antibody producing cells in patients with sickle cell anemia.

B cell function is impaired in patients with sickle cell anemia. Although the number of surface IgM positive cells was similar in sickle cell patients and controls, in vitro spontaneous IgM, and PWM stimulated IgA, IgM, and IgG synthesis was significantly lower in the patients than in controls. The number of PWM induced and antigen specific immunoglobulin producing cells after immunization with Pneumovax, containing 21 serotypes of Streptococcus pneumoniae, was about 100-fold lower in the patients as compared with controls. Finally, the ability of the patients peripheral blood mononuclear cells to proliferate in response to mitogens (PWM, SAC, PHA) was diminished. Because of the observed impairments in both nonspecific and antigen specific immunoglobulin synthesis and cell proliferation assays in the patients, we determined serum concentrations of IL-4 and IL-6, two cytokines associated with antibody production. IL-4 concentrations appeared low in sickle cell patients, and correlated with that of serum IgM. We hypothesize that B cell maturation in sickle cell patients is arrested at an IL-4 dependent stage.

A Screening Test for the Detection of Anti-Hiv-1 IgA in Young Infants

A simple dot blot screening test for anti-HIV-1 IgA in infant sera was developed using recombinant HIV proteins. Ten control infants, 19 uninfected infants of seropositive mothers and 12 HIV culture positive infants were studied at 3 month and 18 month time points. Prior to IgG depletion of the serum samples, 11/12 (92%) of the infected infants, 2/19 (11%) of the uninfected and none of the control infants were anti-HIV IgA positive at 3 months of age. After depletion, no anti-HIV IgA antibodies could be detected in the samples from uninfected infants, whereas the antibodies persisted in all 11 samples from the infected infants, resulting in sensitivity and specificity of 91.7% (95% confidence limits 59.8-99.6%) and 100% (79.1-100%) respectively. The assay might prove useful in the early diagnosis of HIV infection and can be performed at a fraction of the cost of commercially available western blot strips.

Serum levels of soluble CD8, neopterin, β2-microglobulin and p24 antigen as indicators of disease progression in children with AIDS on zidovudine therapy

ObjectiveTo test the hypothesis that serum levels of soluble markers in children change after initiation of zidovudine therapy and that the extent and pattern of these longitudinal changes correlates with clinical outcome. Patients and methodsWe measured serum levels of soluble CD8, neopterin, β2-microglobulin (βM), and p24 antigen, and CD4 cell counts, before the initiation of zidovudine therapy and at 12, 24 and 48 weeks of treatment in 24 HIV-1-infected children (Centers for Disease Control classification P2) and 15 controls. ResultsSoluble CD8 levels were elevated before therapy in 70% of the infected children; subsequent decreases were associated with lower risk of disease progression. The mean serum neopterin level before treatment was elevated in infected children; decreases in neopterin levels marginally reflected improved or stable clinical status. Serum β2M levels and CD4+ cell counts were not associated with clinical outcome. Only 10 out of the 24 patients had detectable levels of serum p24 antigen before treatment; again, the amount of decline after initiation of therapy did not predict clinical outcome. ConclusionDecreasing levels of soluble CD8 and neopterin in HIV-1-infected children receiving zidovudine therapy might reflect a good response to treatment and a slowing of disease progression.