PMID- 36560606 OWN - NLM STAT- MEDLINE DCOM- 20230105 LR - 20230131 IS - 1999-4915 (Electronic) IS - 1999-4915 (Linking) VI - 14 IP - 12 DP - 2022 Nov 23 TI - Chitinase-3-like Protein 1 Is Associated with Poor Virologic Control and Immune Activation in Children Living with HIV. LID - 10.3390/v14122602 [doi] LID - 2602 AB - 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(4)). 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 mug/L (IQR 19-39). CHI3L1 was directly correlated with neutrophil count (rho = 0.22, p = 0.023) and inversely correlated with CD4/CD8 lymphocyte ratio (rho = -0.35, p = 0.00040). Children with detectable viral load had higher levels of CHI3L1 (40 mug/L (interquartile range, IQR 33-44) versus 24 mug/L (IQR 19-35), p = 0.0047). CHI3L1 levels were also correlated with markers of microbial translocation soluble CD14 (rho = 0.26, p = 0.010) and lipopolysaccharide-binding protein (rho = 0.23, p = 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. FAU - Bernard, Isabelle AU - Bernard I AD - Department of Pediatrics, University of Alberta, Edmonton, AB T6G 2R3, Canada. FAU - Ransy, Doris G AU - Ransy DG AD - Unite d'immunopathologie Virale, Centre de Recherche du CHU Sainte-Justine, Montreal, QC H3T 1C5, Canada. FAU - Brophy, Jason AU - Brophy J AUID- ORCID: 0000-0001-9154-8060 AD - Division of Infectious Diseases, Children's Hospital of Eastern Ontario, Ottawa, ON K1H 8L1, Canada. AD - Department of Pediatrics, University of Ottawa, Ottawa, ON K1N 6N5, Canada. FAU - Kakkar, Fatima AU - Kakkar F AD - Department of Pediatrics, CHU Sainte-Justine, Universite de Montreal, Montreal, QC H3T 1C5, Canada. FAU - Bitnun, Ari AU - Bitnun A AD - Division of Infectious Diseases, Hospital for Sick Children, Department of Pediatrics, University of Toronto, Toronto, ON M5G 1X8, Canada. FAU - Samson, Lindy AU - Samson L AD - Division of Infectious Diseases, Children's Hospital of Eastern Ontario, Ottawa, ON K1H 8L1, Canada. FAU - Read, Stanley AU - Read S AD - Division of Infectious Diseases, Hospital for Sick Children, Department of Pediatrics, University of Toronto, Toronto, ON M5G 1X8, Canada. FAU - Soudeyns, Hugo AU - Soudeyns H AUID- ORCID: 0000-0001-5857-3176 AD - Unite d'immunopathologie Virale, Centre de Recherche du CHU Sainte-Justine, Montreal, QC H3T 1C5, Canada. AD - Department of Microbiology, Infectiology & Immunology, Universite de Montreal, Montreal, QC H3T 1J4, Canada. FAU - Hawkes, Michael T AU - Hawkes MT AUID- ORCID: 0000-0002-4122-0937 AD - Department of Pediatrics, University of Alberta, Edmonton, AB T6G 2R3, Canada. AD - School of Public Health, University of Alberta, Edmonton, AB T6G 1C9, Canada. AD - Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, AB T6G 1C9, Canada. AD - Stollery Science Lab, Edmonton, AB T6G 1C9, Canada. AD - Women and Children's Health Research Institute, Edmonton, AB T6G 1C9, Canada. FAU - Epic Study Group AU - Epic Study Group LA - eng GR - HIG-133051/CIHR/Canada PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20221123 PL - Switzerland TA - Viruses JT - Viruses JID - 101509722 RN - 0 (Chitinase-3-Like Protein 1) RN - 0 (CHI3L1 protein, human) SB - IM MH - Adolescent MH - Child MH - Female MH - Humans MH - Male MH - Antiretroviral Therapy, Highly Active MH - Canada MH - CD4 Lymphocyte Count MH - *Chitinase-3-Like Protein 1 MH - Cohort Studies MH - Cross-Sectional Studies MH - *HIV Infections/diagnosis/immunology MH - Viral Load PMC - PMC9786985 OTO - NOTNLM OT - HIV OT - child OT - chitinase-3-like protein 1 OT - inflammation OT - microbial translocation OT - neutrophil COIS- The authors declare no conflict of interest. EDAT- 2022/12/24 06:00 MHDA- 2022/12/27 06:00 PMCR- 2022/11/23 CRDT- 2022/12/23 02:05 PHST- 2022/10/10 00:00 [received] PHST- 2022/11/17 00:00 [revised] PHST- 2022/11/22 00:00 [accepted] PHST- 2022/12/23 02:05 [entrez] PHST- 2022/12/24 06:00 [pubmed] PHST- 2022/12/27 06:00 [medline] PHST- 2022/11/23 00:00 [pmc-release] AID - v14122602 [pii] AID - viruses-14-02602 [pii] AID - 10.3390/v14122602 [doi] PST - epublish SO - Viruses. 2022 Nov 23;14(12):2602. doi: 10.3390/v14122602.