Chitinase-3-like Protein 1 Is Associated with Poor Virologic Control and Immune Activation in Children Living with HIV
Perinatally infected children living with HIV (CLWH) face lifelong infection and associated inflammatory injury. Chitinase-like 3 protein-1 (CHI3L1) is expressed by activated neutrophils and may be a clinically informative marker of systemic inflammation in CLWH. We conducted a multi-centre, cross-s...
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MDPI AG
2022-11-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/14/12/2602 |
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| author | Isabelle Bernard Doris G. Ransy Jason Brophy Fatima Kakkar Ari Bitnun Lindy Samson Stanley Read Hugo Soudeyns Michael T. Hawkes EPIC<sup>4</sup> Study Group |
| author_facet | Isabelle Bernard Doris G. Ransy Jason Brophy Fatima Kakkar Ari Bitnun Lindy Samson Stanley Read Hugo Soudeyns Michael T. Hawkes EPIC<sup>4</sup> Study Group |
| author_sort | Isabelle Bernard |
| collection | DOAJ |
| description | Perinatally infected children living with HIV (CLWH) face lifelong infection and associated inflammatory injury. Chitinase-like 3 protein-1 (CHI3L1) is expressed by activated neutrophils and may be a clinically informative marker of systemic inflammation in CLWH. We conducted a multi-centre, cross-sectional study of CLWH, enrolled in the Early Pediatric Initiation Canadian Child Cure Cohort Study (EPIC<sup>4</sup>). Plasma levels of CHI3L1, pro-inflammatory cytokines, and markers of microbial translocation were measured by enzyme-linked immunosorbent assays. Longitudinal clinical characteristics (viral load, neutrophil count, CD4+ and CD8+ T-lymphocyte counts, and antiretroviral (ARV) regimen) were abstracted from patient medical records. One-hundred-and-five (105) CLWH (median age 13 years, 62% female) were included in the study. Seventy-seven (81%) had viral suppression on combination antiviral therapy (cART). The median CHI3L1 level was 25 μg/L (IQR 19–39). CHI3L1 was directly correlated with neutrophil count (ρ = 0.22, <i>p</i> = 0.023) and inversely correlated with CD4/CD8 lymphocyte ratio (ρ = −0.35, <i>p</i> = 0.00040). Children with detectable viral load had higher levels of CHI3L1 (40 μg/L (interquartile range, IQR 33–44) versus 24 μg/L (IQR 19–35), <i>p</i> = 0.0047). CHI3L1 levels were also correlated with markers of microbial translocation soluble CD14 (ρ = 0.26, <i>p</i> = 0.010) and lipopolysaccharide-binding protein (ρ = 0.23, <i>p</i> = 0.023). We did not detect differences in CHI3L1 between different cART regimens. High levels of neutrophil activation marker CHI3L1 are associated with poor virologic control, immune dysregulation, and microbial translocation in CLWH on cART. |
| first_indexed | 2024-03-09T15:44:24Z |
| format | Article |
| id | doaj.art-08a781a568a6463f940df1ed7467e23a |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-09T15:44:24Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-08a781a568a6463f940df1ed7467e23a2023-11-24T18:36:21ZengMDPI AGViruses1999-49152022-11-011412260210.3390/v14122602Chitinase-3-like Protein 1 Is Associated with Poor Virologic Control and Immune Activation in Children Living with HIVIsabelle Bernard0Doris G. Ransy1Jason Brophy2Fatima Kakkar3Ari Bitnun4Lindy Samson5Stanley Read6Hugo Soudeyns7Michael T. Hawkes8EPIC<sup>4</sup> Study GroupDepartment of Pediatrics, University of Alberta, Edmonton, AB T6G 2R3, CanadaUnité d’immunopathologie Virale, Centre de Recherche du CHU Sainte-Justine, Montreal, QC H3T 1C5, CanadaDivision of Infectious Diseases, Children’s Hospital of Eastern Ontario, Ottawa, ON K1H 8L1, CanadaDepartment of Pediatrics, CHU Sainte-Justine, Université de Montréal, Montreal, QC H3T 1C5, CanadaDivision of Infectious Diseases, Hospital for Sick Children, Department of Pediatrics, University of Toronto, Toronto, ON M5G 1X8, CanadaDivision of Infectious Diseases, Children’s Hospital of Eastern Ontario, Ottawa, ON K1H 8L1, CanadaDivision of Infectious Diseases, Hospital for Sick Children, Department of Pediatrics, University of Toronto, Toronto, ON M5G 1X8, CanadaUnité d’immunopathologie Virale, Centre de Recherche du CHU Sainte-Justine, Montreal, QC H3T 1C5, CanadaDepartment of Pediatrics, University of Alberta, Edmonton, AB T6G 2R3, CanadaPerinatally infected children living with HIV (CLWH) face lifelong infection and associated inflammatory injury. Chitinase-like 3 protein-1 (CHI3L1) is expressed by activated neutrophils and may be a clinically informative marker of systemic inflammation in CLWH. We conducted a multi-centre, cross-sectional study of CLWH, enrolled in the Early Pediatric Initiation Canadian Child Cure Cohort Study (EPIC<sup>4</sup>). Plasma levels of CHI3L1, pro-inflammatory cytokines, and markers of microbial translocation were measured by enzyme-linked immunosorbent assays. Longitudinal clinical characteristics (viral load, neutrophil count, CD4+ and CD8+ T-lymphocyte counts, and antiretroviral (ARV) regimen) were abstracted from patient medical records. One-hundred-and-five (105) CLWH (median age 13 years, 62% female) were included in the study. Seventy-seven (81%) had viral suppression on combination antiviral therapy (cART). The median CHI3L1 level was 25 μg/L (IQR 19–39). CHI3L1 was directly correlated with neutrophil count (ρ = 0.22, <i>p</i> = 0.023) and inversely correlated with CD4/CD8 lymphocyte ratio (ρ = −0.35, <i>p</i> = 0.00040). Children with detectable viral load had higher levels of CHI3L1 (40 μg/L (interquartile range, IQR 33–44) versus 24 μg/L (IQR 19–35), <i>p</i> = 0.0047). CHI3L1 levels were also correlated with markers of microbial translocation soluble CD14 (ρ = 0.26, <i>p</i> = 0.010) and lipopolysaccharide-binding protein (ρ = 0.23, <i>p</i> = 0.023). We did not detect differences in CHI3L1 between different cART regimens. High levels of neutrophil activation marker CHI3L1 are associated with poor virologic control, immune dysregulation, and microbial translocation in CLWH on cART.https://www.mdpi.com/1999-4915/14/12/2602childHIVchitinase-3-like protein 1inflammationneutrophilmicrobial translocation |
| spellingShingle | Isabelle Bernard Doris G. Ransy Jason Brophy Fatima Kakkar Ari Bitnun Lindy Samson Stanley Read Hugo Soudeyns Michael T. Hawkes EPIC<sup>4</sup> Study Group Chitinase-3-like Protein 1 Is Associated with Poor Virologic Control and Immune Activation in Children Living with HIV Viruses child HIV chitinase-3-like protein 1 inflammation neutrophil microbial translocation |
| title | Chitinase-3-like Protein 1 Is Associated with Poor Virologic Control and Immune Activation in Children Living with HIV |
| title_full | Chitinase-3-like Protein 1 Is Associated with Poor Virologic Control and Immune Activation in Children Living with HIV |
| title_fullStr | Chitinase-3-like Protein 1 Is Associated with Poor Virologic Control and Immune Activation in Children Living with HIV |
| title_full_unstemmed | Chitinase-3-like Protein 1 Is Associated with Poor Virologic Control and Immune Activation in Children Living with HIV |
| title_short | Chitinase-3-like Protein 1 Is Associated with Poor Virologic Control and Immune Activation in Children Living with HIV |
| title_sort | chitinase 3 like protein 1 is associated with poor virologic control and immune activation in children living with hiv |
| topic | child HIV chitinase-3-like protein 1 inflammation neutrophil microbial translocation |
| url | https://www.mdpi.com/1999-4915/14/12/2602 |
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