{"id":31354,"date":"2017-02-27T12:09:47","date_gmt":"2017-02-27T12:09:47","guid":{"rendered":"http:\/\/i-base.info\/htb\/?p=31354"},"modified":"2017-03-13T17:01:14","modified_gmt":"2017-03-13T17:01:14","slug":"soluble-cd163-as-a-marker-of-cmv-mediated-immune-activation","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/31354","title":{"rendered":"Soluble CD163 as a marker of CMV mediated immune activation"},"content":{"rendered":"

Gareth Hardy, HIV i-Base<\/strong><\/p>\n

Cytomegalovirus (CMV) may be a driver of harmful immune activation in HIV positive people, even after more than one year of successful ART, according to a study by Serena Vita and colleagues who investigated the relationship between plasma markers of immune activation and CMV serostatus in HIV positive people.<\/strong> [1]<\/p>\n

Residual immune activation that persists after ART is a major concern because it is likely to play a role in age-related degenerative conditions such as dementia and cardiovascular disease. [2]<\/p>\n

Vita and colleagues enrolled matched CMV+\/HIV+ and CMV\u2013\/HIV+ people at a 2:1 ratio from the ICONA (Italian COhort Na\u00efve of Antiretrovirals) Foundation Study cohort, which is a multicentre prospective HIV observational study. Participants underwent CMV serology at enrolment and plasma samples were taken for immunological testing at least one year after successful ART-induced suppression of viral load to below detection and increases in CD4 cell count to above 200 cells\/mm3<\/sup> blood. There was also an HIV negative control group who were almost all CMV+.<\/p>\n

The researchers compared the levels of systemic inflammatory mediators that promote chronic inflammation such as TNF-alpha, IL-6, soluble (s) CD163 and sCD14, which have been shown to be independent predictors of morbidity and mortality in HIV infected people. While TNF-alpha and IL-6 are inflammatory cytokines produced by blood monocytes and their tissue-residing matured descendants macrophages, surface-bound CD163 and CD14 can be shed from monocytes and macrophages as a soluble protein following activation by pro-inflammatory stimuli.<\/p>\n

A total of 69 HIV+ participants were recruited, 46 of whom were CMV+ and 23 CMV\u2013, along with 16 HIV negative controls, of whom 12 were CMV+. Plasma levels of sCD163 were significantly higher in the CMV+\/HIV+ group compared with the CMV\u2013\/HIV+ group (p<0.0001) or the HIV negative control group (p<0.0001). In contrast, levels of sCD14, IL-6 and TNF-alpha were not significantly different between CMV+\/HIV+ people and CMV\u2013\/HIV+ people.<\/p>\n

Plasma levels of sCD163 also correlated with levels of plasma CMV-specific IgG antibodies (r=0.49, p=0.0006). In addition, plasma CMV IgG antibodies correlated with IL-6 (r=0.42, p=0.0041) and TNF-alpha (r=0.34, p=0.021) but not sCD14.<\/p>\n

Furthermore, differences were observed in traditional markers of HIV disease progression between those with HIV\/CMV co-infection and those who were HIV+ without CMV infection. CD8 cell counts were significantly increased in CMV+\/HIV+ people in contrast to CMV\u2013\/HIV+ people (p <0.0001).<\/p>\n

CD4:CD8 ratios were lower for those with CMV\/HIV co-infection (p <0.0001) compared to the CMV\u2013\/HIV+ group. Plasma CMV IgG antibody levels inversely correlated with CD4:CD8 ratios (r=0.40, p=0.0063) as well as with CD4 cell count (r= \u20130.39, p=0.0006) in CMV positive\/HIV positive people. sCD163 levels inversely correlated with CD4:CD8 ratios (r=-0.38, p=0.0075). Interestingly, the researchers also found that the duration of HIV infection correlated with sCD163 levels for those with HIV and CMV coinfection (r=0.29, p=0.04), but not for who were CMV\u2013\/HIV+, suggesting that the two viral infections interact over time to cause monocyte\/macrophage activation.<\/p>\n

Elevated sCD163 levels have been described both as a marker of HIV activity before and after ART [3], as well as with ART-associated co-morbidities such as neurocognitive disorder. [4]<\/p>\n

While the sample sizes in this report are small, the association of sCD163 with CMV\/HIV coinfection described here suggests that CMV may be an important driver of macrophage activation which in turn critically contributes to inflammatory degenerative co-morbidities in HIV positive people, despite viral suppression with ART.<\/p>\n

References:<\/p>\n

    \n
  1. Vita S et al. Soluble CD163 in CMV infected and uninfected subjects on virologically- suppressive antiretroviral therapy in the ICONA cohort. JAIDS (2017) EPub Ahead of Print: DOI: 10.1097\/QAI.0000000000001232
    \nhttps:\/\/www.ncbi.nlm.nih.gov\/pubmed\/27828874<\/a><\/li>\n
  2. Deeks S et al. HIV infection, antiretroviral treatment, ageing, and non-AIDS related morbidity. BMJ (2009) 338:a3172.
    \n    http:\/\/www.bmj.com\/content\/338\/bmj.a3172<\/a><\/li>\n
  3. Burdo TH et al. Soluble CD163 made by monocyte\/macrophages is a novel marker of HIV activity in early and chronic infection prior to and after anti-retroviral therapy. J Infect Dis (2011) 204(1):154-63.
    \n    https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC3105035\/pdf\/jir214.pdf<\/a>\u00a0(PDF)<\/li>\n
  4. Burdo TH et al. Elevated sCD163 in plasma but not cerebrospinal fluid is a marker of neurocognitive impairment in HIV infection. AIDS (2013) 27(9):1387-1395.
    \n    http:\/\/europepmc.org\/backend\/ptpmcrender.fcgi?accid=PMC3844286&blobtype=pdf<\/a>\u00a0(PDF)<\/li>\n<\/ol>\n","protected":false},"excerpt":{"rendered":"

    Gareth Hardy, HIV i-Base Cytomegalovirus (CMV) may be a driver of harmful immune activation in HIV positive people, even after more than one year of successful ART, according to a study by Serena Vita and colleagues who investigated the relationship …<\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[15],"tags":[],"class_list":["post-31354","post","type-post","status-publish","format-standard","hentry","category-basic-science-and-immunology"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/31354","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/comments?post=31354"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/31354\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=31354"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=31354"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=31354"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}