Sialoadhesin (CD169) Expression in CD14+ Cells Is Upregulated Early after HIV-1 Infection and Increases during Disease Progression

BACKGROUND: Sialoadhesin (CD169, siglec-1 or Sn) is an activation marker seen on macrophages in chronic inflammatory diseases and in tumours, and on subsets of tissue macrophages. CD169 is highly expressed by macrophages present in AIDS-related Kaposi's sarcoma lesions. It is also increased on blood monocytes of HIV-1 infected patients with a high viral load despite antiretroviral treatment. METHODOLOGY/PRINCIPAL FINDINGS: We investigated expression of sialoadhesin in untreated HIV-1 and HHV-8 infected patients, by real-time PCR and FACS analysis to establish its expression in relation to infection and disease progression. Patients analysed were either HIV-1 seroconverters (n = 7), in the chronic phase of HIV-1 infection (n = 21), or in the AIDS stage (n = 58). Controls were HHV-8 infected, but otherwise healthy individuals (n = 20), and uninfected men having sex with men (n = 24). Sialoadhesin mRNA was significantly elevated after HIV-1, but not HHV-8 infection, and a further increase was seen in AIDS patients. Samples obtained around HIV-1 seroconversion indicated that sialoadhesin levels go up early in infection. FACS analysis of PBMCs showed that sialoadhesin protein was expressed at high levels by approximately 90% of CD14(+) and CD14(+)CD16(+)cells of HIV-1(+) patients with a concomitant 10-fold increase in sialoadhesin protein/cell compared with uninfected controls. CONCLUSIONS/SIGNIFICANCE: We have shown that sialoadhesin is induced to high levels on CD14(+) cells early after HIV-1 infection in vivo. The phenotype of the cells is maintained during disease progression, suggesting that it could serve as a marker for infection and probably contributes to the severe dysregulation of the immune system seen in AIDS

Gene expression profile of AIDS-related Kaposi's sarcoma

BACKGROUND: Kaposi's Sarcoma (KS) is a proliferation of aberrant vascular structures lined by spindle cells, and is caused by a gammaherpes virus (HHV8/KSHV). Its course is aggravated by co-infection with HIV-1, where the timing of infection with HIV-1 and HHV8 is important for the clinical outcome. METHODS: In order to better understand the pathogenesis of KS, we have analysed tissue from two AIDS-KS lesions, and from normal skin by serial analysis of gene expression (SAGE). Semi-quantitative RT-PCR was then used to validate the results. RESULTS: The expression profile of AIDS-related KS (AIDS-KS) reflects an active process in the skin. Transcripts of HHV8 were found to be very low, and HIV-1 mRNA was not detected by SAGE, although it could be found using RT-PCR. Comparing the expression profile of AIDS-KS tissue with publicly available SAGE libraries suggested that AIDS-KS mRNA levels are most similar to those in an artificially mixed library of endothelial cells and leukocytes, in line with the description of KS lesions as containing spindle cells with endothelial characteristics, and an inflammatory infiltrate. At least 64 transcripts were found to be significantly elevated, and 28 were statistically downregulated in AIDS-KS compared to normal skin. Five of the upregulated mRNAs, including Tie 1 and sialoadhesin/CD169, were confirmed by semi-quantitative PCR to be elevated in additional AIDS-KS biopsies. Antibodies to sialoadhesin/CD169, a known marker of activated macrophages, were shown to specifically label tumour macrophages. CONCLUSION: The expression profile of AIDS-KS showed 64 genes to be significantly upregulated, and 28 genes downregulated, compared with normal skin. One of the genes with increased expression was sialoadhesin (CD169). Antibodies to sialoadhesin/CD169 specifically labelled tumour-associated macrophages, suggesting that macrophages present in AIDS-KS lesions belong to a subset of human CD169+ macrophages

Cytomegalovirus and human herpesvirus 8 DNA detection in peripheral blood monocytic cells of AIDS patients: Correlations with the presence of Kaposi's sarcoma and CMV disease

To establish the effect of the presence in blood cells of cytomegalovirus (CMV) and human herpesvirus 8 (HHV8) DNA, two herpesviruses that are activated frequently in AIDS patients, were selected from the Amsterdam Cohort Studies on HIV/AIDS 181 PBMC samples from patients with and without Kaposi's sarcoma (KS), and with and without CMV-related disease. The viral loads of both HHV8 and CMV were determined by real-time PCR at the time of diagnosis of AIDS. There was no significant difference in prevalence and load for CMV between the KS and non-KS patients. The variable related most strongly to KS was the presence of HHV8 DNA in PBMCs, whilst CMV DNA was related to the development of CMV disease and shortened survival. The frequency of detection of HHV8 increased when the patient presented with more severe KS symptoms at diagnosis, but detection of HHV8 DNA did not influence survival. Therefore, HHV8 and CMV DNA measured in the blood of AIDS patients, are each related mainly to the associated disease, and have no additional predictive value in these patients. (c) 2005 Wiley-Liss, In

Optical follow-up study of 32 high-redshift galaxy cluster candidates from Planck with the William Herschel Telescope

International audienceThe Planck satellite has detected cluster candidates via the Sunyaev Zel’dovich (SZ) effect, but the optical follow-up required to confirm these candidates is still incomplete, especially at high redshifts and for SZ detections at low significance. In this work, we present our analysis of optical observations obtained for 32 Planck cluster candidates using ACAM on the 4.2-m William Herschel Telescope. These cluster candidates were pre-selected using SDSS, WISE, and Pan-STARRS images to likely represent distant clusters at redshifts z ≳ 0.7. We obtain photometric redshift and richness estimates for all of the cluster candidates from a red-sequence analysis of r-, i-, and z-band imaging data. In addition, long-slit observations allow us to measure the redshifts of a subset of the clusters spectroscopically. The optical richness is often lower than expected from the inferred SZ mass when compared to scaling relations previously calibrated at low redshifts. This likely indicates the impact of Eddington bias and projection effects or noise-induced detections, especially at low-SZ significance. Thus, optical follow-up not only provides redshift measurements, but also an important independent verification method. We find that 18 (7) of the candidates at redshifts z > 0.5 (z > 0.8) are at least half as rich as expected from scaling relations, thereby clearly confirming these candidates as massive clusters. While the complex selection function of our sample due to our pre-selection hampers its use for cosmological studies, we do provide a validation of massive high-redshift clusters particularly suitable for further astrophysical investigations