Hierarchy of Baby-Linked Immunogenetic Risk Factors in the Vertical Transmission of Hepatitis C Virus

Abstract

Mother-to-infant transmission of Hepatitis C Virus (HCV) represents the major cause of pediatric HCV infection today. Immunogenetic influence has been poorly investigated and mainly confined to HLA-class II serological polymorphisms. Among 290 parities, 135 from Pavia and 155 from Bergamo, of HCV-RNA-infected Italian women, 21 babies (7.24%) were HCV-RNA positive at birth and steadily positive over 20 months of life. All the 21 infected babies and 44 randomly selected uninfected ones, born to HCV-RNA+ mothers but steadily negative for HCV-RNA during a follow-up of 2 years, and their mothers were investigated for HLA-G, -C, -DRB1, -DQA1 and -DQB1 genomic polymorphisms. Among the different covariates, HLA-Cw*07, -G*010401, -DRB1*0701, -DRB1*1401 and homozygosity for HLA-G 14bp deletion can be considered as risk factors for HCV vertical transmission. On the contrary, protection was conferred by the HLA-DQB1*06, -G*0105N, -Cw*0602, DRB1*1104 and -DRB1*1302 alleles. Our initial question was: has the immunogenetic profile any role in the protection of the fetus growing in an infected milieu and, if so, is it independent from the other non-immunogenetic parameters? The answer to both questions should be yes.

Upregulation of soluble and membrane-bound human leukocyte antigen G expression is primarily observed in the milder histopathological stages of chronic hepatitis C virus infection

“…Previous studies revealed that polymorphic sites at the 3= untranslated region of the HLA-G gene, which are potentially associated with the magnitude of HLA-G production, have been associated with risk factors for the vertical transmission of HCV [13] and susceptibility to HCV infection in sickle cell disease patients [14]. Recently, Weng et al reported that plasma soluble HLA-G levels were dramatically altered in individuals with chronic HCV infection; however, expression of HLA-G in live and its role in HCV infection remain unknown [15].…”

Heterogeneous Pathways of Maternal-fetal Transmission of Human Viruses (Review)

“…One may conclude on the basis of the above findings, that the uptake and transcytosis of viruses examined up to now is very different from the mechanisms detected in differentiated human cells [117]. Lipid rafts seem to possess a crucial role in the transcytosis of viruses in fetal cells.…”

“…The perinatal infection of the newborn babies has been recognised first in the case of papillomaviruses [27,38,164,165,174], herpesviruses [12,50,70,112,143,152,196,197], TT virus [29], hepatitis B virus (HBV), HIV and hepatitis C virus (HCV) [112,117,147,169] during delivery. Molecular characterisation of viruses in sexual partners [196] and that in the parents and neonates [102,165,183,196,197] supported perinatal transmission, too.…”

Factors Affecting the Response to Interferon Alpha Therapy in Egyptian HCV Patients

“…Fanning et al (2001) reported that individuals who possess the alleles DRB1*0701 and/or DQB1*0201 have a relatively stable viral load over time. Also DRB1*07 and DQB1*02 were found by Wawrzynowicz-Syczewska et al (2000) in responsive patients and Jiao and Wang (2003) found a higher response rate to IFN in patients with the HLA-DRB1*07 allele where Martinetti et al (2006) reported that DRB1*13 allele was significant in protection from chronic HCV especially the protection from vertical transmission in infants born to HCV positive mothers.…”