MaryAnn Fletcher

Hypocholesterolemia is associated with immune dysfunction in early human immunodeficiency virus-1 infection

PURPOSE Patients with the acquired immunodeficiency syndrome exhibit marked disturbances in lipid metabolism. Because altered lipid metabolism may affect immune processes, this study characterized the lipid profile of asymptomatic individuals infected with the human immunodeficiency virus (HIV-1), in relationship to immune function. PATIENTS AND METHODS Serum levels of triglycerides and cholesterol were determined in 94 asymptomatic HIV-1-infected (Centers for Disease Control stage II, III) homosexual men and 42 healthy seronegative control subjects. Immune assessment included measurements of lymphocyte subpopulations (CD4), immune activation (beta 2-microglobulin), natural killer cell function, and lymphocyte proliferation in response to mitogens phytohemagglutinin and pokeweed. Dietary intake was determined using a semiquantitative food frequency questionnaire. RESULTS Despite greater consumption of saturated fat and cholesterol, significantly lower levels of total, high-density, and low-density lipoprotein cholesterol were observed in HIV-1-seropositive men, relative to seronegative controls (p < 0.05), with 40% of the HIV-1-infected group demonstrating hypocholesterolemia (less than 150 mg/dL). Low values of total, high-density, and low-density cholesterol were associated with elevated levels of beta 2-microglobulin in HIV-1-seropositive men. No difference between the groups was noted for serum triglycerides. HIV-1-infected subjects did not demonstrate the significant inverse relationship between cholesterol and mitogen response observed in seronegative controls. CONCLUSIONS These findings indicate that low levels of cholesterol are prevalent during the early stages of HIV-1 infection and associated with specific alterations in immune function, suggesting that hypocholesterolemia may be a useful marker of disease progression.

Cognitive-behavioral stress management buffers decreases in dehydroepiandrosterone sulfate (DHEA-S) and increases in the cortisol:DHEA-S ratio and reduces mood disturbance and perceived stress among HIV-seropositive men

This study examined the effects of a 10-week cognitive-behavioral stress management (CBSM) intervention on dehydroepiandrosterone sulfate (DHEA-S) levels and the ratio of cortisol to DHEA-S (cortisol/DHEA-S), potential surrogate adrenal markers of HIV disease progression, in relation to alterations in mood and distress. HIV-seropositive men were randomized to either a group-based CBSM intervention (n = 43) or to a wait-list control group (n = 24), with both hormonal and distress measures assessed just prior to and immediately following the 10-week period. Results showed that CBSM buffers decreases in DHEA-S and increases in the cortisol/DHEA-S ratio. Further examination also revealed that changes in the cortisol/DHEA-S ratio were significantly and positively related to changes in total mood disturbance and perceived stress over time. These findings demonstrate that a short-term CBSM intervention can buffer against decrements in DHEA-S and increments in the cortisol/DHEA-S ratio among symptomatic, HIV-positive men, and that alterations in the cortisol/DHEA-S ratio move in concert with changes in mood and distress observed during CBSM.

Elevated IgE level in relationship to nutritional status and immune parameters in early human immunodeficiency virus–1 disease☆☆☆★★★

Elevation of IgE has been associated with T-cell dysregulation and with the occurrence of opportunistic infections in patients with acquired immunodeficiency syndrome. The precise cause of IgE overproduction during the early stages of human immunodeficiency virus (HIV)-1 disease, however, has not been established. In light of reports demonstrating that IgE production may be affected by vitamin E levels in an animal model, we evaluated nutritional status in relationship to plasma IgE levels and immune parameters in 100 asymptomatic HIV-1-seropositive and 42 HIV-1-seronegative homosexual men. Approximately 18% of the HIV-1-seropositive population demonstrated biochemical evidence of plasma vitamin E deficiency (< 5 micrograms/ml). Subsequent analysis of available samples indicated a dramatic elevation of IgE levels (308 +/- 112 IU/ml) in vitamin E-deficient seropositive subjects (n = 9) as compared with age and CD4-matched HIV-1-seropositive persons with adequate vitamin E levels (n = 16, 118.1 +/- 41.1 IU/ml) and significantly lower levels (59.5 +/- 15.7 IU/ml) in HIV-1-seronegative men (n = 20, p = 0.01). This effect, which was independent of CD4 cell count, did not appear to be influenced by atopic or gastrointestinal parasitic disease. The low plasma vitamin E levels were related at least in part to dietary intake (r = 0.552, p = 0.01), suggesting that supplementation may be warranted in HIV-1-infected persons in whom vitamin E deficiency develops. Analysis of covariance revealed a strong relationship between IgE levels and CD8 cell counts (p < 0.006), and between IgE level and vitamin E deficiency (p < 0.039).(ABSTRACT TRUNCATED AT 250 WORDS)

Renal Involvement in Essential Mixed Cryoglobulinemia

Essential mixed cryoglobulinemia (EMC) is infrequently recognized in this country. We report studies performed in six patients with EMC evaluated by us over the last 6 years. Purpura was present in three patients and glomerulonephritis in all. Two patients had chronic hepatitis B infection. Positive cryoglobulins and C1q binding, hypocomplementemia (especially low C4), positive rheumatoid factor titer, and negative anti-DNA antibodies were characteristic laboratory findings. The cryoprecipitate had strongly positive rheumatoid factor activity and contained a monoclonal IgM, kappa type in one of the two patients evaluated. The predominant lesion by renal biopsy was mesangiocapillary glomerulonephritis type I; electron microscopy revealed typical fibrillar structures in four cases. The above-mentioned features help distinguish EMC from other forms of glomerulonephritis.

Diagnosis of Human Immunodeficiency Virus Infection Using an Immunoglobulin E-Based Assay

ABSTRACT Immunoglobulin assays that are sensitive and specific for detecting human immunodeficiency virus type 1 (HIV-1) infection are especially important in developing countries where PCR and viral culture may not be readily available. Immunoglobulin E (IgE), which is elevated in HIV-1 infection, is the only antibody that does not cross the placenta, making it potentially valuable for viral detection in both children and adults. This study developed an assay for detection of HIV specific IgE antibodies in adults. A total of 170 serum samples from 170 adults (116 HIV positive and 54 HIV negative) were analyzed. Serum or plasma samples were treated by using the protein G affinity method. The HIV status was determined by using two IgG enzyme-linked immunosorbent assays (ELISAs) and one Western blot evaluation. The IgE enzyme immunoassay test for HIV-1 correctly identified the HIV status in 98.8% of the samples (168 of 170). One false-positive and one false-negative test occurred with the IgE ELISA, as well as with the IgG ELISA test but were correctly identified by the IgE test. Analysis of the data demonstrated a high specificity (99%) and sensitivity (99%) of the IgE test, with 95% confidence intervals. The IgE assay appears to be sensitive and specific, suggesting that IgE-specific antibodies offer an effective method to detect HIV-1 infection in adults.

IgE-based assay for early detection of HIV-1 infection in infants.

5Serum samples were collected from patients with HFRS in the Tula region during the outbreak and from convalescent patients (collected between 1 month and 4 years after disease) in the Tula and Ryazan regions. Initial serological screening by immunofluorescence assay (IFA) revealed higher antibody titres to Hantaan, Seoul, 5 and DOB (N Apekina, unpublished) antigens than to Puumala. These findings indicated that a hantavirus other than Puumala virus was the causative agent of the outbreak. In our study of 22 hantavirus-IgG-positive serum samples, as confirmed by ELISA with Puumala, DOB, and Hantaan antigens, 2 all showed the highest reactivities to DOB. However, since previous studies have identified high levels of crossreactive antibodies to several hantaviruses by IFA or ELISA analysis, the serum samples were further assayed by focus-reduction neutralisation test which allows precise serotyping. To avoid misleading crossreactivity of neutralising antibodies during the acute phase of HFRS, 2 only samples from convalescent patients obtained more than 1 month after onset of disease, were selected. Nine such samples were analysed against the hantaviruses known to cause HFRS and the putatively apathogenic Tula virus (table). All serum samples showed high specificities of neutralising antibodies to DOB, confirming its involvement in the Tula-Ryazan outbreak. Our results do not confirm the previously proposed involvement of Seoul virus in the outbreak because none of the serum samples showed significant titres to this hantavirus.