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

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.

HLA-B, HLA-C and KIR improve the predictive value of IFNL3 for Hepatitis C spontaneous clearance

“…Specifically, Ruiz-Extremera et al . found that the children of mothers with KIR3DS1 had a higher risk of HCV chronicity than the children of mothers without this receptor (75% and 19%, respectively) 24 . In our study, the presence of the KIR3DS1 receptor was also linked with chronic HCV infection, showing a higher frequency in patients who had chronic HCV infections (86.2%).…”

“…also found that KIR2DS3 was the principal gene related to HCV viral persistence 16 . A study of risk for mother-to-child transmission of HCV found that KIR3DS1 was associated with development of chronic HCV infection 24 . Specifically, Ruiz-Extremera et al .…”

Human leucocyte antigen but not KIR alleles and haplotypes associated with chronic HCV infection in a Chinese Han population

“…In China, approximately 40 million individuals are infected with hepatitis C virus (HCV), and it is estimated that 50%–to 85% have developed CHC, while 20%–30% of these patients will progress to liver cirrhosis that may lead to hepatocellular carcinoma (J. Li & Zhuang, ). Up to now, the mechanism of CHC and its haematological progress is not clear; however, the host immune system genes, such as human leucocyte antigen (HLA) genes, and their killer‐cell immunoglobulin‐like receptors (KIR) genes could play a role in HCV clearance and the development of CHC (Marangon et al, ; Mozer‐Lisewska et al, ; Ruiz‐Extremera et al, ; Sung et al, ).…”

“…human leucocyte antigen (HLA) genes, and their killer-cell immunoglobulin-like receptors (KIR) genes could play a role in HCV clearance and the development of CHC (Marangon et al, 2011;Mozer-Lisewska et al, 2016;Ruiz-Extremera et al, 2017;Sung et al, 2011).…”

Neonatal Exposure to Hepatitis C Virus Antigens in Uninfected Children Born to Infected Mothers

“…HLA-mismatch between a mother and her child has been described as favorable with regard to vertical viral transmission, since the child´s immune cells has better chance to recognize and kill the virus if its immune system is different from its mother's. HLA-mismatch and the presence of certain HLA-types have been shown to reduce the rate of vertical transmission of HCV-VT, but the findings are contradicting (43,135,136). It has been demonstrated that maternal neutralizing HCVantibodies are not protective of HCV-VT (137,138).…”