Maadhava Ellaurie

Cellular immune factors associated with mother-to-infant transmission of HIV

ObjectiveTo study a possible correlate of protection in mother-to-infant transmission of HIV infection. In particular, to determine whether lack of HIV-specific T-helper (TH) function as indicated by HIV and non-HIV antigen-stimulated interleukin (IL)-2 production of mother and/or newborn peripheral blood leukocytes (PBL) is associated with mother-to-infant transmission of HIV. MethodsPBL from 21 HIV-seropositive pregnant women and 23 cord blood leukocytes (CBL) from their offspring were studied for in vitro TH function by IL-2 production in response to HIV and non-HIV antigens. Polymerase chain reaction (PCR) and viral culture assays were performed to determine HIV infection of the infants. ResultsPBL from 10 out of 21 (48%) mothers and from eight out of 23 (35%) CBL samples responded to two or more out of five synthetic gp160 envelope (env) peptides. Three of the 23 (13%) offspring were shown to be HIV-infected by PCR and/or viral culture on follow-up. All three infected infants were from a subset whose CBL did not exhibit env-specific TH immunity. ConclusionOur results demonstrate that fetal T cells can be primed to HIV env determinants in utero, suggest that HIV-specific TH immunity may be protective in newborns, and provide a possible means for identifying newborns who are at risk for HIV infection.

HIV DNA blood levels in vertically infected pediatric patients: variations with age, association with disease progression, and comparison with blood levels in infected mothers.

Blood levels of HIV DNA in our vertically infected pediatric patients typically followed a characteristic age-related pattern: continuously increasing with increasing age to a peak between ages 4 and 8 months, and thereafter rather steadily declining. Median HIV DNA levels peaked about 3 months earlier in children who by age 24 months developed more severe rather than less severe HIV disease. Children at particular risk of developing severe HIV disease by age 24 months commonly had > 800 HIV DNA copies per 0.1 ml of blood at age 3 weeks to 2 months, > 1,000 copies at 2 to 4 months, and > 2,500 copies at ages 4 to 6 months. Near the time of delivery mothers who transmitted HIV had significantly higher median blood levels of HIV DNA than mothers who did not transmit, but median HIV DNA levels in infected mothers as a group were low compared with those in pediatric patients > or = 1 month of age.

Platelet-associated IgG in pediatric HIV infection.

Hematologic abnormalities, including thrombocytopenia, are seen in HIV infection. We have previously reported elevated platelet-associated IgG (PAIgG) in thrombocytopenia in children associated with human immunodeficiency virus (HIV). In this study we prospectively monitored 40 HIV-infected infants and children to determine the significance of elevated PAIgG levels as they relate to thrombocytopenia. We also examined platelet eluates for the presence of HIV antibody and antigen. Of 16 patients with thrombocytopenia, 15 (93.7%) had elevated PAIgG. Of 24 patients with normal platelet counts, 21 (87.5%) had elevated PAIgG. On follow-up, none of the children with normal platelet counts and elevated PAIgG levels developed thrombocytopenia. Examination of the platelet eluates was negative for HIV antibody or P24 antigen. Although the sensitivity of an elevated PAIgG level in predicting thrombocytopenia is 93%, its specificity is only 13%. Elevated PAIgG levels are therefore not causally related to the development of thrombocytopenia in children.

Reproductive Immunology of Human Immunodeficiency Virus (HIV‐1) Infection

Infection with HIV leads to profound immunosuppression, infection, and malignancy that has wide ranging implications on reproduction in both males and females, which will be explored in this review

119 Simplified human whole blood assay for measurement of dust mite specific gamma interferon production in vitro

A simplified microassay for the measurement of spontaneous and dust mite antigen-induced gamma interferon (IFN) production in vitro using unseparated human blood has been developed. Gamma IFN in 72-hour culture supernatants was measured using a solid phase radioimmunoassay. Maximum production in allergic patients occurred between 25 and 50 micrograms/mL of mite antigen. Both spontaneous and antigen-stimulated levels were highest in the group of mite-allergic patients compared with nonallergic patients or normal controls. Gamma IFN production was lower in a group of mite-allergic patients on immunotherapy compared with the nonimmunotherapy group. Treatment with even small doses of oral corticosteroids completely obliterated both spontaneous and stimulated gamma IFN production. These results indicate that this whole blood assay coupled with a lymphokine radioimmunoassay is a convenient, rapid, and sensitive method for measuring cell-mediated immunity to allergens and responses to IT or drug treatment that can be easily adapted to testing large number of patients.

EFFECT OF IVIG ON CIRCULATING IMMUNE COMPLEXES (CIC) IN PEDIATRIC AIDS/ARC

CIC were studied by Raji cell assay in 23 patients with AIDS and ARC before and after IVIG. All patients had elevated CIC prior to initiative IVIG treatment. Patients were followed for an average of 20 months during which time they received biweekly infusions of Cutter IVIG, A significant reduction of CIC following IVIG was found in 13 patients, 2 of whom subsequently died during follow-up. In 10 other patients there was an increase of CIC after IVIG treatment. This group exhibited a mortality rate of 70%. There was a good correlation between elevated CIC and decreased antigenic and mitogenic responses, low T4/T8 ratio and evidence of viral infection with EBV, CMV and Herpes. Among those patients in whom CIC decreased following IVIG, 33% showed some restoration of mitogen induced proliferation. In contrast, the group that had increased CIC showed no such improvement. No correlation between the level of serum IgG and M and CIC-IgG and CIC-IgM was found and no uniform differences in CIC-IgG or CIC-IgM were observed after IVIG. The mean concentration of IgG and IgM in CIC was 54mg% and 32mg% respectively. After treatment with IVIG the molecular weight of the CIC had decreased from a pre IVIG level of 2 million.

HEMATOLOGIC MANIFESTATIONS OF PEDIATRIC AIDS

The hematologic manifestations of 100 pediatric patients with AIDS/ARC were reviewed. Acute or chronic anemia was present in 94% of all patients. Two patients had autoimmune hemolytic anemia and 1 patient had an aplastic anemia. A positive Coombs test was detected in 40% of all patients. Leukopenia and neutropenia occurred in 50% and 40% of patients respectively. Antineutrophil antibodies were detected in 2 patients. Ten of 13 children developed neutropenia on Bactrim. Forty percent of all children were lymphopenic. Monocytosis and eosinophilia occurred in 66% and 40% of patients respectively. Thrombocytopenia was seen in 33% and of these 25% developed a persistent thrombocytopenia. Platelet antibodies were detected in 10 of 11 patients. Pancytopenia occurred in 20% of children with opportunistic infection (O.I.). Acquired Von Willebrands disease and autoantibodies to Factors X, XI and XII were seen in 2 individuals. Peripheral smears revealed ovalocytes, microcytosis, hypochromia and atypical lymphocytes. Bone marrow examination showed hypercellularity, myeloid hyperplasia and increased plasma cells and lymphocytes. Decreased erythropoeisis, dysmyelopoeisis, dyserythropoeisis and megaloblastic changes were occasionally seen. Bone marrow cultures were positive for mycobacterium avium intra cellulare (4), Candida (2) and CMV (1) in a total of 7 patients.