The incidence of acquired immunodeficiency syndrome (AIDS) in children is increasing, the source of infection usually being the mother. Approximately 75% children with HIV infection are offspring of IV drug abuser parent(s). Diagnosis of HIV infection in newborns and asymptomatic infants is, however, a problem because all infants born to HIV seropositive woemen have passively transferred maternal antibodies which may persist up to and even beyond 15 months of age. Infected and uninfected infants thus cannot be distingushed on the basis of routine immunological or serological testing. A hypothesis of this proposal is that HIV infected infants have HIV-specific B & T cells whose properties can be exploited in-vitro to enable the distrinction between infected and uninfected infants. Novel tests of HIV-specific immunity (in- vitro HIV antibody synthesis, antibody clonotype pattern and HIV antigen specific lymphoproliferation) will be coupled with tests for the polymerase chain reaction, HIV viral cultures and HIV antigen in a multi-test diagnostic approach to this probolem. HIV infection in the pediatric population results in a wide spectrum of clinical and immunologic distrubances, ranging from asymptomatic to severely ill and form immunocompetent to severely immunocompromised status. Main target systems attacked by HIV are the immune system and the nervous system. A second hypothesis to be tested is that rapidity of disease progression is closely linked to initial clinical presentation and laboratory findings. Systematic investigations of the neurological and immunological status, HIV-specific immunity and HIV antigen levels will provide insights into the clinical, virologic and immunologic spectrum in this disease. An important feature of this investigation will be data management. The ability of diagnosing HIV infection in infancy and an understanding of the mechanisms involved in disease progression should bring us closer to developing and monitoring therapeutic strategies against this deadly disease.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA005161-02
Application #
3211288
Study Section
Special Emphasis Panel (SRCD (09))
Project Start
1989-04-01
Project End
1994-03-31
Budget Start
1990-05-01
Budget End
1991-03-31
Support Year
2
Fiscal Year
1990
Total Cost
Indirect Cost
Name
North Shore University Hospital
Department
Type
DUNS #
City
Manhasset
State
NY
Country
United States
Zip Code
11030
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Chirmule, N; Wang, X P; Hu, R et al. (1994) Envelope glycoproteins of HIV-1 interfere with T-cell-dependent B cell differentiation: role of CD4-MHC class II interaction in the effector phase of T cell help. Cell Immunol 155:169-82
McCloskey, T W; Oyaizu, N; Coronesi, M et al. (1994) Use of a flow cytometric assay to quantitate apoptosis in human lymphocytes. Clin Immunol Immunopathol 71:14-8
Chirmule, N; Kalyanaraman, V S; Pahwa, S (1994) Signals transduced through the CD4 molecule on T lymphocytes activate NF-kappa B. Biochem Biophys Res Commun 203:498-505
Wang, X P; Paul, M; Tetali, S et al. (1994) Improved specificity of in vitro anti-HIV antibody production: implications for diagnosis and timing of transmission in infants born to HIV-seropositive mothers. AIDS Res Hum Retroviruses 10:691-9
Chirmule, N; Kalyanaraman, V S; Lederman, S et al. (1993) HIV-gp 160-induced T cell-dependent B cell differentiation. Role of T cell-B cell activation molecule and IL-6. J Immunol 150:2478-86

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