Biomedical subjects

A Scott Laney

Publications and source records attributed to A Scott Laney.

5 recordsLinked to original sources

PubMed2006

Use of a multiantigen detection algorithm for diagnosis of Kaposi's sarcoma-associated herpesvirus infection.

The ability to readily and accurately diagnose Kaposi's sarcoma-associated herpesvirus (KSHV, or human herpesvirus 8) infection in individuals remains a demanding task. Among the available diagnostic methods, sensitivities and specificities range widely, and many are inadequate for large-scale screening studies. We examined a serological algorithm for detecting KSHV in human sera having high sensitivity and specificity. This method uses previously described open reading frame (ORF) K8.1 and ORF65 peptide-based enzyme-linked immunosorbent assays and a novel purified recombinant full-length LANA1 protein. We generated two multiantigen algorithms: one that maximized sensitivity and one that maximized specificity. These serological algorithms were then used to evaluate seroprevalence rates among populations of clinical and epidemiological importance. The serological algorithms yielded sensitivities of 96% and 93% and specificities of 94% and 98% for the more sensitive and specific algorithms, respectively. Among kidney donors, seroprevalence was low, 4.0% (2/50), and similar to that of blood donors (P = 0.46; odds ratio [OR], 1.4; confidence interval [CI], 0.14 to 7.9) using the highly specific algorithm. Using the sensitive algorithm, 8.0% (4/50) were infected compared to 6.4% (16/250) observed among blood donors (OR, 1.3; CI, 0.41 to 4.0; P = 0.43). Among subjects requiring bone marrow transplantation, seroprevalence rates were not elevated compared to those of blood donors (OR, 2.0; 95% CI, 0.10 to 122.9; P = 0.50). Because the need for high-quality KSHV detection methods are warranted and because questions remain about the optimal methods for assessing KSHV infection in individuals, we propose a systematic approach to standardize and optimize the assessment of KSHV infection rates using a combination of established and novel serological assays and methods.

Algorithms↗

PubMed2005

Kaposi sarcoma-associated herpesvirus and primary and secondary pulmonary hypertension.

BACKGROUND: Kaposi sarcoma-associated herpesvirus (KSHV) has been implicated as a factor in the pathogenesis of primary pulmonary hypertension (PPH). We conducted a case-control study of patients with PPH and pulmonary hypertension (PH) associated with other disorders (secondary PH) to look for evidence of KSHV infection. MATERIALS AND METHODS: The study population was composed of patients with a diagnosis of PH at the University of California San Francisco Medical Center Department of Cardiology between July and November 2003. Serologic testing for KSHV was performed using enzyme-linked immunosorbent assays based on peptides from open reading frame-65 and K8.1, using sera from 19 patients with PPH, 29 patients with secondary PH, and 150 control subjects RESULTS: The overall seroprevalence of KSHV among all study participants was 2.0%. The rate among control subjects was 0.7% (1 of 150 subjects); among the study participants with PPH, we found no evidence of KSHV infection (0 of 19 patients). There was no significant difference between the observed seroprevalence of KSHV among patients with PPH compared to control subjects (p = 0.89). Of the 29 patients with a diagnosis of secondary PH, 3 patients (10.3%) were KSHV seropositive. Significantly, two of the three KSHV-infected secondary PH patients were also HIV positive, a known independent risk factor for KSHV infection and secondary PH. CONCLUSION: Our data do not support KSHV infection having a significant role in PPH or non-HIV-associated secondary PH compared to age- and gender-matched control subjects.

Antibodies, Viral↗

PubMed2004

Repeated measures study of human herpesvirus 8 (HHV-8) DNA and antibodies in men seropositive for both HHV-8 and HIV.

OBJECTIVE: To study the natural history and pathogenesis of human herpesvirus 8 (HHV-8) infection in HHV-8-seropositive, immunosuppressed men. DESIGN: Longitudinal study of 87 HHV-8- and HIV-seropositive men [42 with Kaposi's sarcoma (KS)] during four visits over a 2 month period. METHODS: : Patients provided oral fluid and blood. HHV-8 antibody titers were measured with peptide-based enzyme-linked immunosorbent assays (ELISA) for ORF65 and K8.1; HHV-8 DNA was detected with polymerase chain reaction ELISA. RESULTS: HHV-8 DNA was present in oral fluid or peripheral blood mononuclear cells (PBMC) at one or more of the four visits in 71% of men with KS and 56% of men without KS. The strongest correlate of HHV-8 DNA in PBMC was the presence of KS [odds ratio (OR), 8.7; 95% confidence interval (CI), 3.4-22]. Detection of HHV-8 DNA in oral fluid or PBMC was often intermittent, but individuals who shed virus at one time point were more likely to shed at other times. Some men had incomplete epitope recognition in their anti-HHV-8 antibody response. High antibody titers were associated with the absence of circulating HHV-8, particularly for the ORF65 seroassay (OR, 0.16; 95% CI, 0.05-0.51). CONCLUSIONS: Among HHV-8 seropositive men, circulating virus is common even in the absence of disease. The link between KS and HHV-8 DNA in PBMC suggests that anti-herpes drugs may impede KS development or progression. Seroassays should target multiple epitopes to achieve maximal sensitivity. HHV-8 replication may be limited by high antibody titers or other immune function for which antibodies are a marker.

Adult↗

PubMed2004

Evidence for both lytic replication and tightly regulated human herpesvirus 8 latency in circulating mononuclear cells, with virus loads frequently below common thresholds of detection.

To address whether human herpesvirus 8 (HHV-8) DNA in peripheral blood mononuclear cells (PBMCs) might be the product of latent or lytic infection and to shed light on sporadic detection of HHV-8 DNA in individuals seropositive for the virus, we studied the frequency of infected cells, total virus load, and virus load per infected cell in PBMCs from men coinfected with HHV-8 and human immunodeficiency virus (HIV), some of whom had Kaposi's sarcoma. The low frequencies of infected cells detected (fewer than one per million cells in some individuals) suggest that the prevalence of the virus in circulating leukocytes was underestimated in previous studies that employed more conventional sampling methods (single, small-volume specimens). Mean virus loads ranged from 3 to 330 copies per infected PBMC; these numbers can represent much higher loads in individual lytically infected cells (>10(3) genomes/cell) in mixtures that consist predominantly of latently (relatively few genomes) infected cells. The presence in some subjects of high HHV-8 mean genome copy numbers per infected cell, together with viral DNA being found in plasma only from subjects with positive PBMCs, supports earlier suggestions that the virus can actively replicate in PBMCs. In some individuals, mean virus loads were less than 10 genomes per infected cell, suggesting a tightly controlled purely latent state. HHV-8 genome copy numbers are substantially higher in latently infected cells derived from primary effusion lymphomas; thus, it appears that HHV-8 is able to adopt more than one latency program, perhaps analogous to the several types of Epstein-Barr virus latency.

DNA, Viral↗

PubMed2003

Human herpesvirus 8: current issues.

Although human herpesvirus 8 (HHV-8) is the etiologic agent of Kaposi sarcoma (KS), there are no formal guidelines for the clinical management of HHV-8 infection. In patients infected with human immunodeficiency virus (HIV), highly active antiretroviral therapy (HAART) is the best tool for the prevention of KS. In patients who have undergone transplantation, KS is often managed by curtailing immunosuppressive therapies, despite the potential adverse consequences for graft survival. Interventions related to HHV-8 infection might improve the management of KS in immunocompromised patients. However, knowledge from HHV-8 research cannot yet be translated into clinically useful interventions. Achieving clinical utility will require the commercial development of diagnostic tools currently available only in research settings and the evaluation of potential interventions. Such interventions might include the use of HHV-8 diagnostics to identify patients at high risk and to aid in the early detection of KS, prophylaxis with antiherpes drugs to prevent KS, treatment of KS with antiherpes drugs, and donor/recipient screening for organ transplantation.

Anti-HIV Agents↗