2159. IL-6 and CRP Levels are Directly Associated with Monocytic-Myeloid Derived Suppressor Cell Frequencies in HIV(+) Individuals on ART
Session: Poster Abstract Session: HIV Inflammation and Immune Activation
Saturday, October 29, 2016
Room: Poster Hall
Background: The role of myeloid derived suppressor cells (MDSC) in chronic inflammation and immune activation during treated HIV-1 infection has not been fully defined.
Methods: Peripheral blood mononuclear cells (PBMCs) and plasma were obtained from HIV-1(+), CMV antibody(+), participants who are virally suppressed on ART and with CD4+ T cell count >500, along with age-matched, CMV antibody(+), HIV-1-seronegative controls (SNCs) from the Multicenter AIDS Cohort Study. At three time points, frequencies of classical (Lin-CD33+HLA-DR-; cMDSC) and monocytic MDSCs (CD14+CD11b+CD33+HLA-DR-; mMDSC) as well as frequencies of patrolling (CD14dimCD16+) and inflammatory (CD14++CD16+) monocytes in live cells were evaluated using flow cytometry, while levels of sCD14, sCD163, IP-10, IL-6, D-dimer and CRP were measured in plasma using ELISA.
Results: Fifteen HIV(+) and twelve SNCs were enrolled in the study. HIV(+) participants had a median CD4+ T cell count of 803 cells/mm3 (range 555-1355). They had been infected for a median of 9 years and have been virally suppressed for a median of 6 years during the time of enrollment. There were no differences in the frequencies of mMDSCs (p=0.89; Mann-Whitney) and cMDSC (p=0.92) between HIV(+) and SNCs. Frequencies also remained stable across the three timepoints. Although there was an inverse relationship between %patrolling monocytes and %mMDSC in SNCs (r= -0.48; p=0.01; Spearman), this was not observed in HIV(+). Levels of IP-10 (p=0.002) and sCD14 (p<0.001) levels were significantly higher in HIV(+) participants across time points, but did not correlate with cMDSC and mMDSC frequencies. However, in SNCs, a modest negative correlation was seen between IP-10 levels and %mMDSC (r= -0.39; p=0.035). Levels of CRP, IL-6, and sCD163 were similar between the two groups and no correlations were seen between these biomarkers and %cMDSC and %mMDSC in SNCs. However, in HIV(+) participants, plasma levels of IL-6 and CRP directly correlated with %mMDSC (r=0.43; p=0.004 and r =0.40; p=0.011, respectively).
Conclusion: Increases in levels of systemic inflammation markers IL-6 and CRP correlate with higher frequencies of mMDSC in treated, chronic HIV infection, indicating the importance of immunoregulatory mechanisms in HIV.
Christopher Shoff, MD, Internal Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, Cynthia Klamar-Blain, MS, University of Pittsburgh, Pittsburgh, PA, Arcadio Agudelo Hernandez, MD, University of Pittsburgh Medical Center, Pittsburgh, PA, Yue Chen, Ph.D., Infectious Diseases and Microbiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA, Charles Rinaldo, PhD, University of Pittsburgh Schools of the Health Sciences and UPMC, Pittsburgh, PA and Bernard Macatangay, MD, Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pittsburgh, PA
None A. Agudelo Hernandez,
None Y. Chen,
None C. Rinaldo,
None B. Macatangay,