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S H Kleinman

Publications and source records attributed to S H Kleinman.

At least 37 records · Page 2Linked to original sources

A method for estimating hepatitis B virus incidence rates in volunteer blood donors. National Heart, Lung, and Blood Institute Retrovirus Epidemiology Donor Study.

BACKGROUND: Calculations of the incidence of hepatitis B virus (HBV) infections in the blood donor setting that are based solely on data for seroconversion to hepatitis B surface antigen (HBsAg) will underestimate the incidence due to the transient nature of antigenemia. Estimates based on antibody to hepatitis B core antigen will overestimate the incidence due to false-positive results caused by the nonspecificity of the test. STUDY DESIGN AND METHODS: Serologic test results were obtained from multiple-time volunteer donors at five United States blood centers from January 1991 through December 1993. The observed HBsAg seroconversion rate was multiplied by an adjustment factor, derived from the weighted average probability of a positive HBsAg test for HBV-infected donors who become chronic carriers, for donors with a primary antibody response without detectable antigenemia, and for donors who develop transient antigenemia. RESULTS: Among 586,507 multiple-time donors giving 2,318,356 donations and observed for 822,426 person-years, the HBsAg incidence rate was 4.01 per 100,000 person-years. On the basis of prior reports of the duration of HBsAg positivity and the observed distribution of interdonation intervals among the study group, there was an estimated 53-percent chance that an HBV-infected donor with transient antigenemia would have a positive HBsAg test result. If 70 percent of newly HBV-infected adults have transient antigenemia, 25 percent have a primary antibody response without primary antigenemia, and 5 percent become chronic carriers, the overall chance of being detected by the HBsAg test was 42 percent, for an adjustment factor of 2.38. The total HBV incidence rate, therefore, was estimated to be 9.54 per 100,000 person-years. CONCLUSION: The crude HBV incidence rate observed from HBsAg test results will underestimate the true rate. The adjusted HBV incidence rate should be used in applications such as estimations of residual HBV risk to the blood supply and projections of the benefits of screening for HBV DNA.

Adult↗

The risk of transfusion-transmitted viral infections. The Retrovirus Epidemiology Donor Study.

BACKGROUND: Accurate estimates of the risk of transfusion-transmitted infectious disease are essential for monitoring the safety of the blood supply and evaluating the potential effect of new screening tests. We estimated the risk of transmitting the human Immuno-deficiency virus (HIV), the human T-cell lymphotropic virus (HTLV), the hepatitis C virus (HCV), and the hepatitis B virus (HBV) from screened blood units donated during the window period following a recent, undetected infection. METHODS: Using data on 586,507 persons who each donated blood more than once between 1991 and 1993 at five blood centers (for a total of 2,318,356 allogeneic blood donations), we calculated the incidence rates of seroconversion among those whose donations passed all the screening tests used. We adjusted these rates for the estimated duration of the infectious window period for each virus. We then estimated the further reductions in risk that would result from the use of new and more sensitive viral-antigen or nucleic acid screening tests. RESULTS: Among donors whose units passed all screening tests, the risks of giving blood during an infectious window period were estimated as follows: for HIV, 1 in 493,000 (95 percent confidence interval, 202,000 to 2,778,000); for HTLV, 1 in 641,000 (256,000 to 2,000,000); for HCV, 1 in 103,000 (28,000 to 288,000); and for HBV, 1 in 63,000 (31,000 to 147,000). HBV and HCV accounted for 88 percent of the aggregate risk of 1 in 34,000. New screening tests that shorten the window periods for the four viruses should reduce the risks by 27 to 72 percent. CONCLUSIONS: The risk of transmitting HIV, HTLV, HCV, or HBV infection by the transfusion of screened blood is very small, and new screening tests will reduce the risk even further.

Antibodies, Viral↗

Demographic determinants of hepatitis C virus seroprevalence among blood donors.

OBJECTIVE: To measure demographic determinants of hepatitis C virus (HCV) seroprevalence among blood donors in the United States. DESIGN: Cross-sectional epidemiological study. SETTING: Five blood centers in different regions of the United States. SUBJECTS: A total of 862,398 consecutive volunteer blood donors with one or more nonautologous donations from March 1992 through December 1993. METHODS: Demographic data collection, serological screening with second-generation anti-HCV enzyme immunoassay, and confirmation with anti-HCV recombinant immunoblot. RESULTS: There were 3126 donors with at least one blood donation confirmed HCV-seropositive, for a crude prevalence of 3.6 per 1000. Age-specific HCV seroprevalence rose from 0.5 per 1000 donors younger than 20 years to a maximum of 6.9 per 1000 in donors aged 30 to 39 years and declined in older age groups. There was interaction between age and educational attainment, with 30- to 49-year-olds with less than a high school diploma at highest risk of HCV infection (odds ratio [OR], 33.0; 95% confidence interval [CI], 23.0 to 47.2 compared with those younger than 30 years with a bachelor's degree or higher degree). Other independent risk factors for HCV seropositivity included male sex (OR, 1.9; 95% CI, 1.8 to 2.1), black race (OR, 1.7; 95% CI, 1.6 to 1.9), Hispanic ethnicity (OR, 1.3; 95% CI, 1.1 to 1.5), previous blood transfusion (OR, 2.8; 95% CI, 2.5 to 3.1), and first/only time donor status (OR, 4.2; 95% CI, 3.9 to 4.5 compared with repeat donors). Seropositivity for human T-lymphotropic virus types I and II, human immunodeficiency virus, or hepatitis B core antigen was highly associated with HCV seropositivity (OR, 10.4; 95% CI, 9.6 to 11.4 for one vs no marker). CONCLUSIONS: Despite a low overall HCV prevalence in blood donors in the United States, there is a marked variation in HCV seroprevalence by demographic subgroup, even after controlling for prior blood transfusion, a recognized risk factor for HCV. Further study of the prevalence of other parenteral risk factors such as past injection drug use among blood donors is needed.

Adult↗

Frequency of human immunodeficiency virus (HIV) infection among contemporary anti-HIV-1 and anti-HIV-1/2 supplemental test-indeterminate blood donors. The Retrovirus Epidemiology Donor Study.

BACKGROUND: Follow-up studies from the mid-1980s showed that 1 to 5 percent of blood donors testing reactive in anti-human immunodeficiency virus type 1 (HIV-1) enzyme immunoassay (EIA) and testing indeterminate in Western blot were infected with HIV-1 and were in the process of seroconverting. The present study was conducted to establish the rate of HIV infection among contemporary anti-HIV-1/HIV type 2 (HIV-2) EIA-reactive, Western blot-indeterminate donors. STUDY DESIGN AND METHODS: Donations (n = 607) with indeterminate HIV supplemental test results were identified by screening 3,021,342 donations given from November 1990 through August 1993 at five participating blood centers. Consenting donors were enrolled and samples taken 4 to 8 weeks after donation. Follow-up sera were tested by EIA and Western blot for anti-HIV-1 seroconversion and by type-specific peptide assays for antibodies to HIV-2 and HIV-1 subtype O. Peripheral blood mononuclear cells and/or plasma from the follow-up samples were tested for HIV-1 DNA and/or RNA by polymerase chain reaction. The rate of HIV-1 infection among Western blot-indeterminate donors was also estimated by multiplying the incidence rate of HIV-1 seroconversion in this donor population by the estimated duration of the EIA-reactive and Western blot-indeterminate window during seroconversion (8.5 days). RESULTS: Supplemental test-indeterminate donors (n = 355) enrolled a median of 38 days after donation; 265 (75%) of these donors were identified as indeterminate after an anti-HIV-1/2 EIA-reactive donation. Enrolled and non-enrolled donors had similar distributions of demographic characteristics and band patterns. Follow-up samples from all 355 donors tested negative for HIV-1 in polymerase chain reaction. Follow-up sera tested Western blot-negative in 54 cases (15%) and Western blot-indeterminate in 299 (84%). Two follow-up sera (0.6%) were interpreted, according to manufacturer's package insert criteria, as Western blot positive with p24 and gp41 bands and/or gp120/160 bands; however, paired testing of index and follow-up sera from these two cases showed identical Western blot and EIA reactivity, and polymerase chain reaction was negative for HIV RNA and DNA, which ruled out HIV infection. The absence of HIV infection in 355 Western blot-indeterminate donors was consistent with our incidence-based model analysis, which yielded an estimate of one HIV-1 infection for every 215 Western blot-indeterminate donations (95% CI, 1/39-1/8333). CONCLUSION: Contemporary blood donors classified as indeterminate in supplemental HIV testing are infrequently infected with HIV. Donors whose follow-up samples test negative in anti-HIV-1/2 EIAs and negative or persistently indeterminate in Western blots should be considered eligible for reinstatement.

Adult↗

Relationship between antibody to hepatitis B core antigen and retroviral infections in blood from volunteer donors.

BACKGROUND: The value of the test for antibody to hepatitis B core antigen (anti-HBc) as a surrogate screening assay in the time before sensitive, virus-specific screening tests were available has been well established. There is significant debate, however about the residual value of anti-HBc screening after the implementation of human immunodeficiency virus (HIV)-, human T-lymphotrophic virus (HTLV)-, and hepatitis C virus (HCV)-specific assays and, in particular, about its utility as a lifestyle marker to identify persons at risk for retrovirus infections. STUDY DESIGN AND METHODS: Screening tests for antibodies to HIV, HTLV, and HBc, as well as confirmatory or supplemental test results for anti-HIV and anti-HTLV, were obtained from approximately 2.8 million donations collected from 1991 through 1993 by five blood centers within the United States. The sensitivity, positive predictive value, and relative prevalence of anti-HBc for each retrovirus were calculated and compared among demographic subgroups. RESULTS: The overall relationship between anti-HBc and anti-HIV was similar to that between anti-HBc and anti-HTLV. When calculated from the measured endpoint of the prevalence of anti-HIV-positive and anti-HTLV-positive donations, the sensitivities were 31.1 and 26.2 percent, the positive predictive values were 0.18 and 0.21 percent, and the relative prevalences were 30.1 and 23.8, respectively. Among 27 anti-HIV-seroconverting donors and 9 anti-HTLV-seroconverting donors, the sensitivities were 7.4 percent (95% CI: 0.9-24.3%) and 0 percent (95% CI: 0.0-28.3%), respectively. It was estimated that for each HIV-infected window-period donation detected by anti-HBc, from 19,000 to 81,000 HIV-noninfected donations are discarded. Similarly, more than 33,000 HTLV-noninfected donations are likely to be discarded for each HTLV-infected donation detected by anti-HBc. CONCLUSION: Although anti-HBc-reactive donations are more likely to be seropositive for a retrovirus than are anti-HBc-nonreactive donations, the low positive predictive value limits the test's effectiveness. If the anti-HBc test is retained in the blood donor setting, efforts should be focused on reducing the number of false-positive results.

Adolescent↗

Accuracy of supplementary serologic testing for human T-lymphotropic virus types I and II in US blood donors. Retrovirus Epidemiology Donor Study.

Blood donations in the United States have been screened for antibody to human T-lymphotropic virus type I (HTLV-I) by HTLV-I enzyme immunoassay (EIA) since November 1988. Specimens repeatedly found to be reactive by EIA undergo confirmation by supplementary serologic tests. We assessed the accuracy of blood center testing of 994 HTLV-I EIA repeat-reactive specimens in five US blood centers between November 1988 and December 1991. Of 410 confirmed HTLV-I/II donations, 407 (99.3%) were infected with HTLV-I/II, as determined by polymerase chain reaction (PCR) (403 cases) and by repeat serologic testing (4 cases). The three false-positive results occurred in the first year of testing. Of 425 HTLV-indeterminate specimens, 6 (1.4%) were found to be infected by PCR (5 with HTLV-II and 1 with HTLV-I). None of 159 confirmatory test-negative donations was PCR positive. Of HTLV-I/II-seropositive specimens, 80.2% to 95.4% could be typed as HTLV-I or HTLV-II by type-specific serologic assays. These results support recommendations that HTLV-I/II-seropositive donors should be advised that they are infected with HTLV-I, HTLV-II, or HTLV-I/II (depending on results of type-specific assays). HTLV-indeterminate donors should be advised that their results only rarely indicate HTLV infection. HTLV confirmatory test-negative donors should be reassured that they are not infected with HTLV-I or HTLV-II.

Blood Donors↗

Epidemiologic background and long-term course of disease in human immunodeficiency virus type 1-infected blood donors identified before routine laboratory screening. Transfusion Safety Study Group.

BACKGROUND: The long-term course of human immunodeficiency virus type 1 (HIV-1)-related disease among seropositive blood donors has not been described. The enrollment and epidemiologic background of HIV-1-infected donors in the Transfusion Safety Study and their immunologic and clinical progression are described. STUDY DESIGN AND METHODS: Through the testing of approximately 200,000 sera from donations made in late 1984 and early 1985, 146 anti-HIV-1-positive donors and 151 uninfected matched donors were enrolled. These two cohorts were followed with 6-month interval histories and laboratory testing. RESULTS: Seropositive donors detected before the institution of routine anti-HIV-1 screening disproportionately were first-time donors and men with exclusively male sexual contacts. The actuarial probability of a person's developing AIDS within 7 years after donation was 40 percent; the probability of a person's dying of AIDS was 28 percent. AIDS developed more often when the donor was p24 antigen-positive at donation. Over a 3-year period, significant decreases occurred in CD4+, CD2+CD26+, CD4+CD29+, and CD20+CD21+ counts, but not in CD8+ subsets, CD20+, or CD14+. CONCLUSION: The high proportions of first-time donations and exclusively homosexual men among seropositive donors suggest that test-seeking may have contributed to the high HIV-1 prevalence in the repository. Implementation of alternative test sites when routine donor screening began in 1985 may have averted many high-risk donations. The disease course in HIV-1-infected donors had the same wide spectrum of immunologic and clinical manifestations as were reported for other cohorts.

Acquired Immunodeficiency Syndrome↗

Transfusion transmission of retroviruses: human T-lymphotropic virus types I and II compared with human immunodeficiency virus type 1.

BACKGROUND: The incidence of transfusion transmission of human T-lymphotropic virus type I (HTLV-I) and HTLV type II (HTLV-II) has not been compared directly or to that of human immunodeficiency virus type 1 (HIV-1). The effects of refrigerator storage of the blood component on infectivity of the viruses needs definition. STUDY DESIGN AND METHODS: The circumstances influencing the transmission of HTLV-I, HTLV-II, and HIV-1 via blood of donors whose sera were stored in a repository and who were retrospectively documented as having been infected at blood donation were examined. Confirmation and typing of anti-HTLV positivity in donors and recipients used polymerase chain reaction, supplemented by specific peptide testing. RESULTS: Overall, 27 percent (26/95) of the recipients of blood components from anti-HTLV-I- and -II-positive donors became infected (9 with HTLV-I and 17 with HTLV-II). No recipients of acellular blood components became infected with HTLV-I or -II. There was no probable transmission by components stored > 10 days. The rates of transmission for both viruses were similar: 0 to 5 days' storage, 17 (74%) of 23; 6 to 10 days, 8 (44%) of 18; and 11 to 14, 0 (0%) of 10 (trend, p = 0.0002). In comparison, 89 percent (112/126) of the recipients of anti-HIV-1-positive blood were infected regardless of component type, and no effect on transmission occurred with storage for < 26 days. CONCLUSION: Transfusion-transmitted HTLV-I and -II are similar. The data suggest that a donor's lymphocytes become noninfectious when they lose the ability to be activated or to proliferate.

Acquired Immunodeficiency Syndrome↗

Evaluation of a p21e-spiked western blot (immunoblot) in confirming human T-cell lymphotropic virus type I or II infection in volunteer blood donors. The Retrovirus Epidemiology Donor Study Group.

Current algorithms for the serologic confirmation of human T-cell lymphotropic virus type I and II (HTLV-I/II) antibody reactivity are complicated. We evaluated the performance of an HTLV-I Western blot (immunoblot) spiked with recombinant p21e protein (p21e WB) as an alternative to current confirmatory methods. These methods include the HTLV-I viral lysate Western blot and either a radioimmunoprecipitation assay or a p21e enzyme-linked immunosorbent assay. Five hundred fifty nine blood donations obtained from five U.S. blood centers and classified as HTLV-I/II seropositive (n = 149) or seroindeterminate (n = 410) by routine testing methods were further evaluated by PCR for proviral DNA and by the p21e WB. On the basis of serologic and PCR testing, 155 donations were classified as HTLV-I/II infected. The sensitivity of the p21e WB was 97.4%, slightly exceeding that of routine confirmatory testing. The specificity of the p21e WB was 97.5%, as determined by testing of 404 seroindeterminate samples that were negative in the PCR. The positive predictive value of the p21e WB was 94%. In contrast, the specificity and positive predictive value of routine confirmatory testing were both 100%. Follow-up sampling of presumptive p21e WB false-positive donors substantiated the absence of HTLV-I/II infection. Although the p21e WB used in this study has high sensitivity and may be useful as a confirmatory assay in epidemiologic research studies, it may not be ideal as a confirmatory test for the notification of blood donors.

Blood Donors↗

Human immunodeficiency virus infection and indeterminate western blot patterns. Prospective studies in a low prevalence population.

Interpretation of human immunodeficiency virus (HIV) antibody results that are "indeterminate" rather than clearly positive or negative is problematic for the person delivering the result as well as for the individual being tested. To improve counseling messages for these individuals, we evaluated data collected from a well-characterized cohort of 387 blood donors who had been monitored for up to 2 years. We sought to determine if persons with indeterminate Western blot patterns were infected with HIV, and whether information derived from follow-up monitoring would assist in the development of counseling messages for persons on whom no follow-up information was available. Donors were studied by laboratory assays, clinical evaluation, and assessment of risk for HIV. The absence of HIV infection in 97 of 98 donors with indeterminate Western blot patterns was confirmed by clinical follow-up, Western blot assays of sequential samples, and negative gene amplification results. We propose supplemental guidelines to be used as an adjunct to existing interpretive criteria for counseling individuals when they first present with an indeterminate Western blot finding.

Acquired Immunodeficiency Syndrome↗

Infection with human immunodeficiency virus type 1 (HIV-1) among recipients of antibody-positive blood donations.

OBJECTIVE: To assess the incidence of human immunodeficiency virus type 1(HIV-1) transmission by antibody (anti-HIV-1)-positive blood components, and to determine the immunologic and clinical course in HIV-1-infected recipients. DESIGN AND SUBJECTS: We retrospectively tested approximately 200,000 donor blood component specimens stored in late 1984 and 1985 for anti-HIV-1, and we contacted recipients of positive specimens to determine their serologic status. They were compared with both recipients of HIV-1-negative transfusions and healthy (untransfused) controls. Subjects were seen at 3- to 6-month intervals for up to 4 years for clinical and immunologic evaluations. MEASUREMENTS AND MAIN RESULTS: Of 133 recipients, 9 had other possible exposures. Excluding these cases, 111 of 124 (89.5%) were anti-HIV-1-positive (95% CI, 84.1% to 94.5%). The recipient's sex, age, underlying condition, and type of component did not influence infection rates. The cumulative risk for developing the acquired immunodeficiency syndrome (AIDS) within 38 months after transfusion was 13% (CI, 7.5% to 21.6%). At 36 +/- 3 months after the index transfusion, seropositive recipients had lower counts of CD2+CDw26+, CD4+, CD4+CD29+, and CD4+CD45RA+subsets and more CD8+I2+ lymphocytes than did recipients of anti-HIV-1-negative transfusions. The CD4+ and CD2+CDw26+subsets changed the most rapidly. The absolute CD8+ count remained normal. CONCLUSIONS: Transfusion of anti-HIV-1-positive blood infected 90% of recipients. The rate of progression to AIDS within the first 38 months after infection was similar to that reported for homosexual men and hemophiliacs. Although most lymphocyte subset counts changed over time, CD8+ counts were constant.

Acquired Immunodeficiency Syndrome↗

Screening of selected male blood donors for p24 antigen of human immunodeficiency virus type 1. The Transfusion Safety Study Group.

BACKGROUND: The p24 antigen of human immunodeficiency virus type 1 (HIV-1) is sometimes detected before antibody (anti-HIV-1) is detectable in the serum of recently infected persons. This has led to the consideration of p24-antigen testing for routine screening of blood donors. METHODS: To estimate how many HIV-infected seronegative donors would be identified if p24-antigen screening was introduced, we tested selected donations from a repository of 200,000 serum samples from voluntary donors that was established in late 1984 and early 1985. The 8597 serum samples selected for p24-antigen screening were chosen because their donors had demographic characteristics known to be associated with a high prevalence of seropositivity. RESULTS: The prevalence of anti-HIV-1 antibodies in the 1984-1985 serum samples selected for p24-antigen screening was 1.54 percent--more than 100 times the 0.012 percent prevalence in present-day donations in the United States. The antigen was detected in 15 of 132 serum samples (11.4 percent) from donors who had already been confirmed as seropositive. No instance of confirmed positivity for p24 antigen was found among the 8465 seronegative serum samples. CONCLUSIONS: These data indicate that the yield of screening for p24 antigen in volunteer donors to identify HIV-1 carriers would be negligible. We therefore recommend against routine screening with currently available p24-antigen assays.

Blood Donors↗

Prevalence of antibodies to human immunodeficiency virus type 1 among blood donors prior to screening. The Transfusion Safety Study/NHLBI Donor Repository.

The Transfusion Safety Study (TSS) and the National Heart, Lung, and Blood Institute (NHLBI) established a repository of approximately 200,000 sera from blood donors in late 1984 and early 1985. Collections were made in the four metropolitan areas with the highest prevalence of AIDS. Retrospective testing showed an overall anti-HIV-1 prevalence of 16 cases per 10,000 donations. In this study, the predictive value of a negative initial enzyme-linked immunoassay was estimated from both quality control specimens and the rescreening of 13,461 sera to be greater than 99.99 percent with respect to technical error. Among anti-HIV-1-positive persons, there was a 1.3- to 1.5-fold excess of first-time donors. The anti-HIV-1 prevalence among donors showed that infection was more common among young men than suggested by national reporting of AIDS cases. Anti-HIV-1 prevalence varied among the four metropolitan areas less than did reported AIDS cases, but, by 1987, the differences in the latter had decreased. Anti-HIV-1 prevalence in collection areas outside of the four major cities differed much more widely than that among the cities themselves. The TSS/NHLBI Donor Repository will remain available for the indefinite future for further evaluation of screening procedures for HIV-1 and other viruses for which transfusion is found to be an important route of transmission.

Acquired Immunodeficiency Syndrome↗

Epidemiologic background of blood donors with antibody to human T-cell lymphotropic virus. Transfusion Safety Study Group.

We interviewed 51 blood donors in four major US metropolitan areas subsequently found to have had antibodies to human T-cell lymphotropic virus (anti-HTLV) in late 1984-early 1985. Sixteen donors (31%) reported that they or a sexual contact had a history of blood transfusion. Twelve donors (24%) reported that they or a sexual contact used intravenous drugs. Ten donors (20%) were blacks born in the southeastern US. Four of the male donors (15%) reported homosexual contact. The most common characteristic was an association with Japan or the Caribbean basin (61%). These results show a broader variation of epidemiologic backgrounds than anticipated.

Adult↗

Transmission of human immunodeficiency virus (HIV) by blood transfusions screened as negative for HIV antibody.

Since early 1985, blood donations in the United States have been screened for antibody to human immunodeficiency virus (HIV). To identify instances of HIV transmission by antibody-negative donations, we investigated 13 persons seropositive for HIV who had received blood from 7 donors who were screened as negative for HIV antibody at the time of donation. Twelve of the 13 recipients had no identifiable risk factors for HIV infection other than the transfusions they had received. On evaluation 8 to 20 months after transfusion, HIV-related illnesses had developed in three recipients, and the acquired immunodeficiency syndrome had developed in one. All seven donors were found to be infected with HIV. On interview, six reported a risk factor for HIV infection, and five had engaged in high-risk activities or had had an illness suggestive of acute retroviral syndrome within the four months preceding their HIV-seronegative donation. Thus, these donors had apparently been infected only recently, and so were negative at the time of blood donation according to available antibody tests. We conclude that there is a small but identifiable risk of HIV infection for recipients of screened blood. To minimize this risk, the reasons for deferral of donation need to be communicated more effectively to blood donors who are at high risk of HIV infection, and new assays that detect HIV infection earlier should be evaluated for their effectiveness in screening donated blood.

Acquired Immunodeficiency Syndrome↗

In vitro activation of T lymphocytes from human immunodeficiency virus (HIV)-seropositive blood donors. I. Soluble interleukin 2 receptor (IL2R) production parallels cellular IL2R expression and DNA synthesis.

We investigated the relationship of soluble interleukin 2 receptor (sIL2R) production to cellular IL2R expression and DNA synthesis by mitogen-stimulated mononuclear cells from blood donors seropositive for human immunodeficiency virus (HIV). SIL2R was measured using an enzyme-linked immunosorbent assay which employed 2 anti-IL2R monoclonal antibodies recognizing distinct IL2R epitopes. Decreased phytohemagglutinin-induced DNA synthesis and cellular IL2R expression were accompanied by decreased levels of sIL2R in cell culture supernatants. Similar findings were observed for pokeweed mitogen-induced responses. There was no detectable spontaneous secretion of sIL2R into culture supernatants by unstimulated mononuclear cells from either HIV-seropositive or control seronegative donors. These findings indicate that the in vitro T-cell activation defects which characterize HIV infection include decreased sIL2R production, as well as decreased cellular IL2R expression and DNA synthesis. Further, they show that assessment of supernatant sIL2R levels can be used as a valid, reliable assay for T-cell activation.

Acquired Immunodeficiency Syndrome↗

CD4 and CD8 subsets defined by dual-color cytofluorometry which distinguish symptomatic from asymptomatic blood donors seropositive for human immunodeficiency virus.

As part of a larger study to characterize immune alterations in blood donors seropositive for human immunodeficiency virus (HIV), we measured subsets of CD4 (T helper/inducer) and CD8 (T suppressor/cytotoxic) cells by 2-color cytofluorometry. Alterations observed in asymptomatic seropositive donors (ASP) included: 1) decreased mean levels of Leu 8+ CD4 cells, although the proportion of Leu 8+ cells within the CD4 population was unchanged; 2) a selective increase in Leu 8- CD8 and Leu 18- CD8 cell levels; and 3) increased levels of both CD8 subsets defined by Leu 7, Leu 17, or HLA-DR expression. Alterations observed in symptomatic seropositive donors (SSP) were: 1) a further decrease in Leu 8+ CD4 cell levels, with a decrease in the proportion of Leu 8+ CD4 cells; 2) decreased levels of both Leu 18- and Leu 18+ CD4 subsets; 3) selective increases in Leu 8- and Leu 18- CD8 cell levels; and 4) increases in Leu 7+ CD8, Leu 17+ CD8, and HLA-DR+ CD8 subsets but not the reciprocal negative CD8 subsets. Thus, changes merely reflective of HIV infection included decreased levels of Leu 8+ CD4 cells and increased levels of Leu 8- CD8, Leu 18- CD8, Leu 7+ CD8, Leu 17+ CD8, and HLA-DR+ CD8 cells. Development of symptoms were associated with a further, preferential loss of Leu 8+ CD4 cells, proportional losses of both CD4 subsets defined by Leu 18 expression, and a return to normal levels of Leu 7- CD8, Leu 17- CD8, and HLA-DR- CD8 cells.

Adult↗