☆ 4.3 Article

Do Biomarkers of Inflammation, Monocyte Activation, and Altered Coagulation Explain Excess Mortality Between HIV Infected and Uninfected People?

JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES (2016)

Journal

JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES

Volume 72, Issue 2, Pages 206-213

Publisher

LIPPINCOTT WILLIAMS & WILKINS

DOI: 10.1097/QAI.0000000000000954

Keywords

HIV; mortality; inflammation; monocyte activation; coagulation

Funding

National Institute on Alcohol Abuse and Alcoholism
National Heart Lung and Blood Institute at the National Institutes of Health [R01HC095136-04 5R01HC095126-04, R01AI110259-01A1, 1I01BX002358-01A1]
National Institute on Alcohol Abuse and Alcoholism [U10 AA 13566]
Gilead
AbbVie

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Abstract

Background: HIV infection and biomarkers of inflammation [measured by interleukin-6 (IL-6)], monocyte activation [soluble CD14 (sCD14)], and coagulation (D-dimer) are associated with morbidity and mortality. We hypothesized that these immunologic processes mediate (explain) some of the excess risk of mortality among HIV infected (HIV+) versus uninfected people independently of comorbid diseases. Methods: Among 2350 (1521 HIV+) participants from the Veterans Aging Cohort Study Biomarker Cohort (VACS BC), we investigated whether the association between HIV and mortality was altered by adjustment for IL-6, sCD14, and D-dimer, accounting for confounders. Participants were followed from date of blood draw for biomarker assays (baseline) until death or July 25, 2013. Analyses included ordered logistic regression and Cox Proportional Hazards regression. Results: During 6.9 years (median), 414 deaths occurred. The proportional odds of being in a higher quartile of IL-6, sCD14, or D-dimer were 2-3 fold higher for viremic HIV+ versus uninfected people. Mortality rates were higher among HIV+ compared with uninfected people [incidence rate ratio (95% CI): 1.31 (1.06 to 1.62)]. Mortality risk increased with increasing quartiles of IL-6, sCD14, and D-dimer regardless of HIV status. Adjustment for IL-6, sCD14, and D-dimer partially attenuated mortality risk among HIV+ people with unsuppressed viremia (HIV-1 RNA >= 10,000 copies per milliliter) compared with uninfected people-hazard ratio (95% CI) decreased from 2.18 (1.60 to 2.99) to 2.00 (1.45 to 2.76). Conclusions: HIV infection is associated with elevated IL-6, sCD14, and D-dimer, which are in turn associated with mortality. Baseline measures of these biomarkers partially mediate excess mortality risk among HIV+ versus uninfected people. milliliter) compared with uninfected people-hazard ratio (95% CI) decreased from 2.18 (1.60 to 2.99) to 2.00 (1.45 to 2.76). Conclusions: HIV infection is associated with elevated IL-6, sCD14, and D-dimer, which are in turn associated with mortality. Baseline measures of these biomarkers partially mediate excess mortality risk among HIV+ versus uninfected people.

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Platelets reprogram monocyte functions by secreting MMP-9 to benefit postoperative outcomes following acute aortic dissection

Wei-Yun Shen, Hui Li, An-Hui Zha, Ru-Yi Luo, Yan-Ling Zhang, Cong Luo, Ru-Ping Dai

Summary: Platelets have the ability to modulate immune responses and are associated with cardiac disease. Despite low platelet counts, platelets in patients with acute aortic dissection (AAD) are activated, leading to significant alterations in immune-modulating mediators. Monocytes in AAD patients have suppressed immune status, which correlates with poor outcomes following surgery. Platelets preferentially aggregate with monocytes, and the levels of monocyte-platelet aggregates (MPAs) are related to postoperative recovery. Platelets restore suppressed monocyte functions by forming aggregates and secreting matrix metalloproteinase-9 (MMP-9), potentially improving postoperative outcomes following complex cardiovascular surgery.

ISCIENCE (2023)