T cell responses and viral variability in blood donation candidates with occult hepatitis B infection

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• 作者：Marta Bes¹ ; ² ; ³ ; Victor Vargas² ; ³ ; ⁴ ; Maria Piron¹ ; ³ ; Natalia Casamitjana¹ ; Juan Ignacio Esteban² ; ³ ; ⁴ ; Nuria Vilanova¹ ; Asuncion Pinacho¹ ; Josep Quer² ; ³ ; ⁴ ; Lluis Puig¹ ; ³ ; Jaime Guardia² ; ³ ; ⁴ ; Silvia Sauleda¹ ; ³ ; ^{ssauleda@bst.cat}
• 关键词：aa ; amino acid ; CBA ; cytometric bead array ; CHB ; chronic hepatitis B ; CTL ; cytotoxic T lymphocytes ; ELISpot ; enzyme linked immunospot assay ; HBcAg ; HBV core antigen ; HBeAg ; HBV e antigen ; HBsAg ; HBV surface antigen ; HBV ; hepatitis B virus ; HLA ; human leuk
• 刊名：Journal of Hepatology
• 出版年：2012
• 期刊代码：162_01688278
• 类别：med
• 出版时间：April, 2012
• 卷：56
• 期：4
• 页码：765-774
• 文件大小：1070 K

摘要

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Background & Aims

Occult HBV infection (OBI) is defined by the presence of HBV DNA in the liver and/or serum and negative HBsAg testing. Since the implementation of highly sensitive HBV DNA screening, OBI is also detected in healthy blood donors. The aims of this study were to investigate HBV-specific immune responses and genetic variability in donors with OBI, established by HBV DNA in serum.

Methods

HBV-specific T-cell responses to HBV antigens were tested in 34 OBI donors by IFN-纬 ELISpot, cytometric bead array, and intracellular cytokine staining. As comparison populations, 36 inactive HBV carriers, 22 donors with spontaneously resolved HBV infection, 24 vaccinated donors, and 25 seronegative donors were also included. Surface, pre-S, and pre-c/core genes from 44 genotype D isolates (24 OBI and 20 HBsAg-positive) were sequenced.

Results

The immune response of OBI donors to the 3 HBV antigens was 29-41%, similar to the response in subjects with resolved HBV infection and higher than that in HBsAg-positive subjects. On sequence analysis, OBI donors presented a higher HBsAg mutation rate than HBsAg-positive subjects. Mutations were clustered in the major hydrophilic region of HBsAg, and no stop codons or relevant mutations that could affect antigen formation or detection were observed.

Conclusions

Our results suggest that immune response can suppress viral replication to low levels and HBsAg expression to undetectable levels in OBI blood donors. Relevant mutations were not found in the genomic HBsAg coding region. Hence, the fact that HBsAg was not detected in OBI is likely due to low HBsAg production, rather than to a failure of laboratory reagents.