# Correlation Analysis Between HLA Polymorphisms and Immune Response to Hepatitis B Vaccine in Children with Acute Lymphoblastic Leukemia

**Authors:** Rui Zhang, Tian Yang, Yijin Gao, Hua Zhang, Yi Fei, Laibao Yang, Pengfei Deng

PMC · DOI: 10.3390/vaccines14020145 · Vaccines · 2026-01-30

## TL;DR

This study found that certain HLA gene variations may affect how well children with leukemia respond to the hepatitis B vaccine.

## Contribution

The study identifies HLA-B*3501 as a novel genetic factor linked to lower vaccine response in leukemia patients.

## Key findings

- Post-vaccination anti-HBs titers were significantly higher than pre-vaccination levels.
- HLA-B*3501 allele was negatively correlated with anti-HBs response levels.
- A low-response group showed significantly lower antibody titers compared to the high-response group.

## Abstract

Background: The human leukocyte antigen (HLA) is crucial for antigen presentation and vaccine efficacy. This study examined the association between HLA polymorphisms and the immune response to hepatitis B vaccination in children with acute lymphoblastic leukemia (ALL). Methods: 101 pediatric ALL patients at Shanghai Children’s Medical Center affiliated with Shanghai Jiaotong University School of Medicine who tested negative for hepatitis B surface antibody (anti-HBs) and were not infected with hepatitis B received three doses of the hepatitis B vaccine. Anti-HBs titers were measured before and after vaccination. Participants were divided into high- and low-response groups based on post-vaccination anti-HBs titers. Sequence-specific primer polymerase chain reaction (PCR-SSP) was used to genotype HLA-A, -B, -Cw, -DRB1, and -DQB1 alleles. Results: Pre-vaccination anti-HBs titers were 3.38 ± 2.97 mIU/mL, and the post-vaccination seroconversion rate was 100% with mean titers of 429.61 ± 303.13 mIU/mL (p < 0.001). Following immunization, the low-response group (11.88%) had an anti-HBs titer of 56.47 ± 28.38 mIU/mL, while the high-response group (88.12%) had an anti-HBs titer of 479.93 ± 287.70 mIU/mL. There were significant differences in allele frequencies of B*3501 and Cw*0303 between the two response groups (p < 0.05). Binary logistic regression analysis showed that the B*3501 allele was negatively correlated with the anti-HBs response level (p < 0.05). Conclusions: HLA-B*3501 may be associated with lower antibody response levels in children with ALL who completed the full hepatitis B vaccination series. All these children demonstrated protection against the hepatitis B virus (HBV). We will subsequently validate the association between HLA-B*3501 and the level of hepatitis B vaccine immune response in children with ALL through expanding the sample size or conducting a multicenter study.

## Linked entities

- **Genes:** HLA-A (major histocompatibility complex, class I, A) [NCBI Gene 3105], HLA-B (major histocompatibility complex, class I, B) [NCBI Gene 3106], HLA-DRB1 (major histocompatibility complex, class II, DR beta 1) [NCBI Gene 3123], HLA-DQB1 (major histocompatibility complex, class II, DQ beta 1) [NCBI Gene 3119]
- **Diseases:** Hepatitis B (MONDO:0005344), Acute Lymphoblastic Leukemia (MONDO:0004967)

## Full-text entities

- **Genes:** HLA-C (major histocompatibility complex, class I, C) [NCBI Gene 3107] {aka D6S204, HLA-JY3, HLAC, HLC-C, MHC, PSORS1}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, HLA-DQB1 (major histocompatibility complex, class II, DQ beta 1) [NCBI Gene 3119] {aka CELIAC1, HLA-DQB, IDDM1}, HLA-A (major histocompatibility complex, class I, A) [NCBI Gene 3105] {aka HLAA}, HLA-B (major histocompatibility complex, class I, B) [NCBI Gene 3106] {aka AS, B-4901, HLAB}, HLA-DPB1 (major histocompatibility complex, class II, DP beta 1) [NCBI Gene 3115] {aka DPB1, HLA-DP, HLA-DP1B, HLA-DPB}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, HLA-DRB1 (major histocompatibility complex, class II, DR beta 1) [NCBI Gene 3123] {aka DRB1, HLA-DR1B, HLA-DRB, SS1}
- **Diseases:** HBV infection (MESH:D006509), infected (MESH:D007239), ALL (MESH:D054198), deaths (MESH:D003643), injury to (MESH:D014947), cirrhosis (MESH:D005355), hepatocellular carcinoma (MESH:D006528), hematological malignancies (MESH:D019337), acute and chronic hepatitis B (MESH:D019694)
- **Chemicals:** anti-HBc (-)
- **Species:** Homo sapiens (human, species) [taxon 9606], Hepatitis B virus (no rank) [taxon 10407]

## Full text

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## Figures

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## References

25 references — full list in the complete paper: https://tomesphere.com/paper/PMC12944832/full.md

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Source: https://tomesphere.com/paper/PMC12944832