Association of Anisocytosis with Markers of Immune Activation and Exhaustion in Treated HIV
Background: Treated HIV infection is associated with heightened inflammation which can contribute to increased risk of cardiovascular disease (CVD). We have previously shown that anisocytosis, as measured by red cell distribution width (RDW), is independently associated with prevalent CVD in people...
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| Format: | Article |
| Language: | English |
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Case Western Reserve University
2017-05-01
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| Series: | Pathogens and Immunity |
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| Online Access: | https://paijournal.com/index.php/paijournal/article/view/199 |
| _version_ | 1818310987381473280 |
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| author | Sadeer G. Al-Kindi David A. Zidar Grace A. McComsey Chris T. Longenecker |
| author_facet | Sadeer G. Al-Kindi David A. Zidar Grace A. McComsey Chris T. Longenecker |
| author_sort | Sadeer G. Al-Kindi |
| collection | DOAJ |
| description | Background: Treated HIV infection is associated with heightened inflammation which can contribute to increased risk of cardiovascular disease (CVD). We have previously shown that anisocytosis, as measured by red cell distribution width (RDW), is independently associated with prevalent CVD in people living with HIV (PLHIV). In this study, we sought to identify immune correlates of RDW in PLHIV receiving antiretroviral therapy.
Methods: We performed a cross-sectional and longitudinal analysis of 147 virally-suppressed PLHIV, who had LDL <130 mg/dL and evidence of heightened inflammation, in a randomized trial of statin therapy. A complete blood count and biomarkers of inflammation and immune activation/exhaustion were measured in peripheral blood at entry and after 24 and 48 weeks. Associations with RDW were estimated using linear regression and linear mixed models.
Results: The median age (IQR) for the cohort at enrollment was 46 (40–53) years; 78% were male and 68% were African American. The median RDW for the cohort was 13.4% (12.9–14.0). Compared with the lowest RDW tertile, patients in the highest tertile were less likely to be male, and more likely to be African American, have lower hemoglobin, lower mean corpuscular volume, and higher platelet counts (all P<0.05). At baseline, RDW weakly correlated with C-reactive protein (r=0.196), d-dimer (r=0.214), fibrinogen (r=0.192), interleukin-6 (r=0.257), CD4+DR+38+ T cells (r=0.195), and CD4+PD1+ T cells (r=0.227), all P<0.05. Only IL-6, CD4+38+DR+ T cells, and CD4+PD1+ T_cells remained associated after adjustment for clinical factors known to affect RDW in the general population. Over 48 weeks, RDW did not change and there was no significant effect of statin (P=0.45). After adjustment for clinical parameters, RDW remained positively associated with CD4+38+DR+ and CD4+PD1+ T cells across all time points (P=0.05).
Conclusion: In this population of treated HIV+ subjects, anisocytosis was associated with biomarkers of inflammation and T-cell activation/exhaustion over time and independent of clinical confounders. Therefore, RDW may be a useful prognostic biomarker of cardiovascular risk that partially reflects chronic inflammation and immune exhaustion in PLHIV receiving antiretroviral therapy. |
| first_indexed | 2024-12-13T07:54:47Z |
| format | Article |
| id | doaj.art-da209707121446df9085bf784113580b |
| institution | Directory Open Access Journal |
| issn | 2469-2964 |
| language | English |
| last_indexed | 2024-12-13T07:54:47Z |
| publishDate | 2017-05-01 |
| publisher | Case Western Reserve University |
| record_format | Article |
| series | Pathogens and Immunity |
| spelling | doaj.art-da209707121446df9085bf784113580b2022-12-21T23:54:34ZengCase Western Reserve UniversityPathogens and Immunity2469-29642017-05-012113815010.20411/pai.v2i1.19951Association of Anisocytosis with Markers of Immune Activation and Exhaustion in Treated HIVSadeer G. Al-Kindi0David A. Zidar1Grace A. McComsey2Chris T. Longenecker3Harrington Heart and Vascular Institute, University Hospitals Cleveland Medical Center, Cleveland, Ohio; School of Medicine, Case Western Reserve University, Cleveland, OhioHarrington Heart and Vascular Institute, University Hospitals Cleveland Medical Center, Cleveland, Ohio; School of Medicine, Case Western Reserve University, Cleveland, OhioSchool of Medicine, Case Western Reserve University, Cleveland, Ohio; Division of Pediatric Infectious Diseases, Rainbow Babies and Children’s Hospitals, Cleveland, OhioHarrington Heart and Vascular Institute, University Hospitals Cleveland Medical Center, Cleveland, Ohio; School of Medicine, Case Western Reserve University, Cleveland, OhioBackground: Treated HIV infection is associated with heightened inflammation which can contribute to increased risk of cardiovascular disease (CVD). We have previously shown that anisocytosis, as measured by red cell distribution width (RDW), is independently associated with prevalent CVD in people living with HIV (PLHIV). In this study, we sought to identify immune correlates of RDW in PLHIV receiving antiretroviral therapy. Methods: We performed a cross-sectional and longitudinal analysis of 147 virally-suppressed PLHIV, who had LDL <130 mg/dL and evidence of heightened inflammation, in a randomized trial of statin therapy. A complete blood count and biomarkers of inflammation and immune activation/exhaustion were measured in peripheral blood at entry and after 24 and 48 weeks. Associations with RDW were estimated using linear regression and linear mixed models. Results: The median age (IQR) for the cohort at enrollment was 46 (40–53) years; 78% were male and 68% were African American. The median RDW for the cohort was 13.4% (12.9–14.0). Compared with the lowest RDW tertile, patients in the highest tertile were less likely to be male, and more likely to be African American, have lower hemoglobin, lower mean corpuscular volume, and higher platelet counts (all P<0.05). At baseline, RDW weakly correlated with C-reactive protein (r=0.196), d-dimer (r=0.214), fibrinogen (r=0.192), interleukin-6 (r=0.257), CD4+DR+38+ T cells (r=0.195), and CD4+PD1+ T cells (r=0.227), all P<0.05. Only IL-6, CD4+38+DR+ T cells, and CD4+PD1+ T_cells remained associated after adjustment for clinical factors known to affect RDW in the general population. Over 48 weeks, RDW did not change and there was no significant effect of statin (P=0.45). After adjustment for clinical parameters, RDW remained positively associated with CD4+38+DR+ and CD4+PD1+ T cells across all time points (P=0.05). Conclusion: In this population of treated HIV+ subjects, anisocytosis was associated with biomarkers of inflammation and T-cell activation/exhaustion over time and independent of clinical confounders. Therefore, RDW may be a useful prognostic biomarker of cardiovascular risk that partially reflects chronic inflammation and immune exhaustion in PLHIV receiving antiretroviral therapy.https://paijournal.com/index.php/paijournal/article/view/199Red cell distribution widthanisocytosisHIVcardiovascular diseaseinflammation |
| spellingShingle | Sadeer G. Al-Kindi David A. Zidar Grace A. McComsey Chris T. Longenecker Association of Anisocytosis with Markers of Immune Activation and Exhaustion in Treated HIV Pathogens and Immunity Red cell distribution width anisocytosis HIV cardiovascular disease inflammation |
| title | Association of Anisocytosis with Markers of Immune Activation and Exhaustion in Treated HIV |
| title_full | Association of Anisocytosis with Markers of Immune Activation and Exhaustion in Treated HIV |
| title_fullStr | Association of Anisocytosis with Markers of Immune Activation and Exhaustion in Treated HIV |
| title_full_unstemmed | Association of Anisocytosis with Markers of Immune Activation and Exhaustion in Treated HIV |
| title_short | Association of Anisocytosis with Markers of Immune Activation and Exhaustion in Treated HIV |
| title_sort | association of anisocytosis with markers of immune activation and exhaustion in treated hiv |
| topic | Red cell distribution width anisocytosis HIV cardiovascular disease inflammation |
| url | https://paijournal.com/index.php/paijournal/article/view/199 |
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