RGD Reference Report - Influence of HLA class I, HLA class II and KIRs on vertical transmission and chronicity of hepatitis C virus in children. - Rat Genome Database

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Influence of HLA class I, HLA class II and KIRs on vertical transmission and chronicity of hepatitis C virus in children.

Authors: Ruiz-Extremera, A  Pavón-Castillero, E J  Florido, M  Muñoz de Rueda, P  Muñoz-Gámez, J A  Casado, J  Carazo, A  Quiles, R  Jiménez-Ruiz, S M  Gila, A  Luna, J D  León, J  Salmerón, J 
Citation: Ruiz-Extremera A, etal., PLoS One. 2017 Feb 22;12(2):e0172527. doi: 10.1371/journal.pone.0172527. eCollection 2017.
RGD ID: 38676472
Pubmed: PMID:28225833   (View Abstract at PubMed)
PMCID: PMC5321427   (View Article at PubMed Central)
DOI: DOI:10.1371/journal.pone.0172527   (Journal Full-text)


BACKGROUND & AIM: There is evidence that maternal viral load of HCV during delivery influences the risk for Mother-to-child transmission (MTCT), but this does not explain all cases. We study the role of the immunogenetic profile (HLA, KIRs and KIR-ligand binding) of mothers and children in HCV-MTCT and in chronicity in the children.
METHODOLOGY: 79 HCV-RNA (+) mothers and their 98 children were included. 24 children were infected, becoming chronic in 8 cases and clearing in 16. HLA-class-I and II and KIRs were determined by Luminex.
RESULTS: MTCT study: The presence of HLA-C1-ligand in mothers and/or their children reduces the risk of transmission (mothers: Pc = 0.011, children: P = 0.033), whereas the presence of HLA-C2C2-ligand in mothers increases it (Pc = 0.011). In children KIR2DL3-HLA-C1 is a protector factor (Pc = 0.011). Chronicity in children study: Maternal DQA1*01 allele (Pc = 0.027), KIR2DS1 (Pc = 0.011) or KIR3DS1 (Pc = 0.011) favours chronicity in the child. The presence of the DQB1*03 allele (Pc = 0.027) and KIR2DS3 (P = 0.056) in the child and homozygosity for KIR3DL1/3DL1 (Pc = 0.011) and for the HLA-Bw4/Bw4 ligand (P = 0.027) is associated with viral clearance, whereas the presence of HLA-Bw6 ligand (P = 0.027), the binding of KIR3DS1-HLA-Bw4 (P = 0.037) and heterozygosity for KIR3DL1/3DS1 (Pc = 0.011) favour viral chronicity. Mother/child allele matching: In the joint HLA analysis, matching was greater between mothers and children with chronic infection vs those who had cleared the virus (67%±4.1 vs 57%±1.2, P = 0.003).
CONCLUSIONS: The HLA-C1 ligand in the mother is related to MTCT, while several genetic factors of the mother or child are involved in the chronification or clearance of infection in the child. Matching allelic data is considered to be an indicator of HCV chronicity in the child and can be used as a potential prognostic test. This implies that NK cells may play a previously undocumented role in protecting against MTCT and that both NK cell immunity and adaptive T-cell responses may influence viral clearance in infected children.



RGD Manual Disease Annotations    Click to see Annotation Detail View
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
KIR3DS1HumanChronic Hepatitis C susceptibilityIAGP DNA:deletion: (human)RGD 
KIR3DL1Humanhepatitis C susceptibilityIAGP DNA:deletion:cdsRGD 
Kir3dl1Rathepatitis C susceptibilityISO DNA:deletion:cdsRGD 
Kir3dl1Mousehepatitis C susceptibilityISO DNA:deletion:cdsRGD 

Objects Annotated

Genes (Rattus norvegicus)
Kir3dl1  (killer cell immunoglobulin like receptor, three Ig domains and long cytoplasmic tail 1)

Genes (Mus musculus)
Kir3dl1  (killer cell immunoglobulin-like receptor, three domains, long cytoplasmic tail, 1)

Genes (Homo sapiens)
KIR3DL1  (killer cell immunoglobulin like receptor, three Ig domains and long cytoplasmic tail 1)
KIR3DS1  (killer cell immunoglobulin like receptor, three Ig domains and short cytoplasmic tail 1)


Additional Information