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Abstract
Background & aimThere 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.Methodology79 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.ResultsMTCT 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).ConclusionsThe 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.
Highlights
Hepatitis C virus (HCV) is a major health problem, affecting 170 million people worldwide
We study the role of the immunogenetic profile (HLA, killer-cell immunoglobulin-like receptor (KIR) and KIR-ligand binding) of mothers and children in HCV-Mother-to-child transmission (MTCT) and in chronicity in the children
The human leucocyte antigen (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
Summary
Hepatitis C virus (HCV) is a major health problem, affecting 170 million people worldwide. Mother-to-child transmission (MTCT) is the major cause of paediatric HCV infection, which is the most common origin of chronic liver disease in children in industrialised countries. One explanation for the low MTCT rate is the small amount of inoculum that the child receives from the mother This would explain why the viral load at the time of birth is an important predictive factor. Few studies have been conducted on the influence of HLA genes on MTCT rate and chronicity or spontaneous clearance in infected children. It is important to perform a complete study of HLA alleles and other genetic factors, such as killer-cell immunoglobulin-like receptors (KIRs), in the mother and the child. 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.
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