Outcomes of a trial of HIV-1 immunogen in patients with HIV infection.
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Biomedical subjects
Publications and source records attributed to R B Stricker.
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BACKGROUND: Chronic Lyme disease (LD) is a debilitating illness caused by tickborne infection with the spirochete Borrelia burgdorferi. Although immunologic abnormalities appear to play a role in this disease, specific immunologic markers of chronic LD have not been identified. METHODS: We evaluated 73 patients with chronic LD for lymphocyte subset abnormalities using flow cytometry. Of these, 53 patients had predominant musculoskeletal symptoms, while 20 patients had predominant neurologic symptoms. The estimated duration of infection ranged from 3 months to 15 years, and all patients had positive serologic tests for B. burgdorferi. Ten patients with acute LD (infection less than 1 month) and 22 patients with acquired immunodeficiency syndrome (AIDS) served as disease controls. RESULTS: All 31 chronic LD patients who were tested prior to antibiotic treatment had significantly decreased CD57 lymphocyte counts (mean, 30+/-16 cells per microl; normal, 60-360 cells per microl, P<0.001). Nineteen of 37 patients (51%) who were tested after initiating antibiotic therapy had decreased CD57 levels (mean, 66+/-39 cells per microl), and all five patients tested after completing antibiotic treatment had normal CD57 counts (mean, 173+/-98 cells per microl). In contrast, all 10 patients with acute LD and 82% of AIDS patients had normal CD57 levels, and the difference between these groups and the pre-treatment patients with chronic LD was significant (P<0.001). Patients with chronic LD and predominant neurologic symptoms had significantly lower mean CD57 levels than patients with predominant musculoskeletal symptoms (30+/-21 vs. 58+/-37 cells per microl, P=0.002). CD57 levels increased in chronic LD patients whose symptoms improved, while patients with refractory disease had persistently low CD57 counts. CONCLUSIONS: A decrease in the CD57 lymphocyte subset may be an important marker of chronic LD. Changes in the CD57 subset may be useful to monitor the response to therapy in this disease.
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Oligonucleotide sequences containing unmethylated cytidine phosphate guanosine (CpG) motifs are known to have significant immunostimulatory properties. Because of these immunostimulatory effects, unmethylated CpG oligonucleotides are thought to act as 'danger signals' that produce a favorable immune response by alerting the host to the presence of invading organisms or abnormal cells. In contrast to this concept, we review the evidence that unmethylated CpG sequences derived either from microbial agents or from endogenous CpG-rich Alu motifs promote disease progression by inducing an aberrant or autoreactive immune response. Recognition of the negative effect of unmethylated CpG dinucleotides should lead to more effective immune strategies to combat infectious, inflammatory, autoimmune and malignant diseases.
Recent descriptions of the first human and chimpanzee cases of human immunodeficiency virus type 1 (HIV-1)-related retroviral infections dating from 1959 have stirred interest in the origin of AIDS. Although the theory of a chimpanzee origin of HIV-1 with cross-species transfer to man has now gained popularity, a more likely scenario is that chimps and humans were infected by an HIV-1 precursor virus derived from a contaminated poliovaccine. The reason for the rapidity and ease of cross-species transfer of this precursor virus has not been elucidated. We hypothesize that the poliovaccine was passaged in a human diploid cell strain. This simple manipulation allowed the retrovirus to adapt to human tissues and may have spawned the AIDS pandemic.
OBJECTIVE: To evaluate the efficacy of low-dose intravenous immunoglobulin (IVIG) treatment in older women with immunologic abnormalities and recurrent spontaneous abortion (RSA), a condition referred to as immunologic abortion. DESIGN: Prospective clinical trial. SETTING: Outpatient referral practice. PATIENT(S): Forty-seven women were enrolled in the study. The mean age of the women was 37 years (range, 28-45 years), and the mean number of prior miscarriages was 3.7. Immunologic abnormalities included antiphospholipid antibodies (32%), antithyroid antibodies (53%), antinuclear antibodies (28%), antiovarian antibodies (2%), increased natural killer cells (40%), increased immunoglobulin (Ig)M level (28%), and increased CD4/CD8 T-cell ratio (15%). One patient had IgA deficiency, and three women had endometriosis. Thirty-one of the 47 patients (66%) had more than one immunologic abnormality. INTERVENTION(S): Treatment with IVIG at a dose of 0.2 g/kg within 2 weeks of attempted conception. Once conception was achieved, IVIG treatment was continued on a monthly basis at the same dose through 26-30 weeks of gestation. MAIN OUTCOME MEASURE(S): Successful pregnancy or recurrent abortion. RESULT(S): Of the 47 women, 36 received initial IVIG treatment, and 24 subsequently became pregnant. Of these women, 20 continued IVIG treatment through 26-30 weeks of gestation, and 19 (95%) had a successful term pregnancy. Four women discontinued IVIG therapy after 10-12 weeks of gestation, and 3 (75%) had a successful pregnancy outcome. Of the 11 women who refused IVIG therapy, 7 became pregnant, and all 7 miscarried. The difference in pregnancy success rate between the IVIG-treated and untreated groups was significant (P=.001). Three women had adverse reactions during the low-dose IVIG infusion, and these reactions resolved when the IVIG brand was changed. Fetal abnormalities were not observed. CONCLUSION(S): Low-dose IVIG therapy is beneficial for older women with immunologic abortion. The optimum duration of IVIG treatment in these women requires further study.
Enhancement of programmed cell death (apoptosis) of CD4 T-cells by human immunodeficiency virus (HIV) is thought to be an important factor in the pathogenesis of HIV disease. Recent studies have cast doubt on this concept, however, portraying apoptosis as a potent antiviral strategy to eliminate infected cells. These studies have shed new light on the role of apoptosis in HIV infection. While cellular and immunologic mechanisms of apoptosis purge the HIV-infected lymphoid cell population, HIV thwarts apoptosis in myeloid cells, particularly monocyte/macrophages. Although HIV protease inhibitor therapy partially reverses the lymphoid cell process, this therapeutic approach fails to counter the persistence of HIV infection in myeloid cells. Thus apoptosis of T-cells may be a futile host attempt to control the spread of HIV while the infection smoulders in monocyte/macrophages. In other words, the antiviral defense system fiddles while the immune system burns.
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