Immune Profiling of Blood Donors with Occult Hepatitis B Virus Infection: Analysis of IL-10, IL-12, TNF-a, and HLA Expression in Abuja, Nigeria
Babandina Muhammad Musa, Mustapha Umar Kalgo, Ibrahim K. Kwaifa, Sule Moses, Charity Obum-Nnadi Ndidi, Patricia Manko Lar
Citation: Babandina Muhammad Musa, Mustapha Umar Kalgo, Ibrahim K. Kwaifa, Sule Moses, Charity Obum-Nnadi Ndidi, Patricia Manko Lar, "Immune Profiling of Blood Donors with Occult Hepatitis B Virus Infection: Analysis of IL-10, IL-12, TNF-a, and HLA Expression in Abuja, Nigeria", OAS Journal of Medical and Health Sciences, Volume 01, Issue 01.
Copyright: This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Background: Occult hepatitis B virus infection (OBI) poses a hidden risk to blood transfusion safety, particularly in regions with high HBV endemicity such as Nigeria. The immunological mechanisms underlying viral persistence in OBI remain poorly defined. Cytokine regulation and HLA molecule expression may play critical roles in shaping host immune responses.
Methods: Blood samples from voluntary donors in Abuja, Nigeria, were screened for OBI using molecular assays. Immunological profiling included quantification of interleukin-10 (IL-10), interleukin-12 (IL-12), and tumor necrosis factor-alpha (TNF-a) levels, alongside assessment of HLA class I and II molecule expression.
Results: Donors with OBI demonstrated significantly elevated IL-10 concentrations, indicating a skew toward immunosuppressive regulation. In contrast, IL-12 and TNF-a levels were reduced, suggesting impaired pro-inflammatory and antiviral activity. Altered HLA class I and II expression patterns were observed, consistent with potential HBV immune evasion strategies.
Conclusion: The immunological profile of OBI donors in Abuja highlights a cytokine imbalance characterized by IL-10 dominance and reduced IL-12/TNF-a activity, coupled with altered HLA expression. These findings suggest that HBV persistence in OBI is facilitated by immune modulation and evasion, underscoring the need for enhanced donor screening and immunologically informed interventions to improve transfusion safety in Nigeria.
Keywords: Cytokines, IL-10, IL-12, TNF-a, MHC-HLA*0201 and OBI.
References:
1. Abakar, M. A. A., Ali, A. A. H., Elhassan, E. D. A., Altaher, E. A. H., Musa, N. H. A., Kafi, S. K., Osman, A. E. F., & Waggiallah, H. A. (2023). Association of TNF-a, IFN-?, IL-6, and IL-10 with different clinical manifestations of hepatitis B infection. Italian Journal of Medicine, 17(2), Article 1627. https://doi.org/10.4081/itjm.2023.1627
2. Abdulqadir, M.O., Rashid, P.M.A., Hussain, A.H., Rahman, H.S., Ezzaddin, S.A. (2023). Genetic characterization of hepatitis B virus genotypes among patients with chronic infection in Sulaimaniyah city, Iraq. PeerJ 11:e14454. http://doi.org/10.7717/peerj.14454
3. Ahmad, A. E., Bakari, A. G., Musa, B. O. P., Mustapha, S. K., Jamoh, B. Y., Abdullahi, I. N., …, Suleiman, A. B. (2019). Pattern of prevalent hepatitis B virus genotypes in Zaria, Nigeria. Nigerian Postgraduate Medical Journal, 6 (2), 80-86.
4. Ajuwon, B. I., Yujuico, I., Roper, K., Richardson, A., Sheel, M. & Ledbury, B.A. (2021). hepatitis B virus infection in Nigeria: A systematic review and meta-analysis of data published between 2010 and 2019. Journal of Biomedicine; Infectious Diseases, 21, 1120 -1129.
5. Akintule, O.A., Olusola, B.A., Odaibo, G.N. and Olaleye, D.O. (2018). Occult HBV Infection in Nigeria Department of Virology. Arch Basic Appl Med. 6(1): 87–93.
6. Ali, A. S., Hussein, N. A., Elmi, E. O., Ismail, A. M. & Abdi, M. M. (2023). Hepatitis B vaccination coverage and Associated factors among medical students: A cross-sectional study in Bosaso, Somalia. Journal of Biomedicine Public Health, 23(1), 1-8.
7. Alkhazashvili, M., Bloch, E. M., Shadaker, S., Kuchuloria, T., Getia, V. & Turdziladze, A. (2023). Advancing blood transfusion safety using molecular detection in the country of Georgia. Transfusion and Clinical Biology, 13 (5), 307-313.
8. Allain, J.P., Owusu-Ofori, S., Ye, X., Bisseye, C., Chaar, M., Li, C. (2022). Hepatitis B virus chronic infection in blood donors from Asian and African high or medium prevalence areas: Comparison according to sex. Viruses, 14 (4), 673-681. doi:10.3390/v14040673.
9. Arababadi, M. K., Pourfathollah, A. A., Jafarzadeh, A. & Hassanshahi, G. (2022). Serum levels of IL10 and IL17A in occult HBV-infected South East Iranian patients. Hepatology, 10 (1), 31-42.
10. Araujo, N. M., Teles, S. A. & Spitz, N. (2020). Comprehensive analysis of clinically significant hepatitis B virus mutations in relation to genotype, sub-genotype and geographic region. Frontier Journal of Microbiology, 11, e616023.
11. Ashsih, G. (2021). Modeling reveals no direct role of the extent of HBV-DNA integrations on the outcome of infection. Journal of theoretical biology. 10 (7) 526.e110793.
12. Ayalew, G., Assefa, A., Amsalu, A., Geta, M., Mihret, A., Aseffa, A. (2019). Immune protection of hepatitis B vaccine among children living in Gondar Town, Northwest Ethiopia. Ethiopian Medical Journal, 2, 139-46.
13. Babandina, M. M., Ocheme, J. O., Musa, S. M., Khadijat, T. M., Amos, D., Maryam, A., Saheed, A., Nura, M. B., Zainab, U., Clara, O., Abbas, M. B., Musa, A. M., Patricia, M. L. (2025). The prevalence of occult hepatitis B virus infection among hepatitis B surface antigen sero- negative blood donors. Sokoto Journal of Medical Laboratory Science; 10(1): 135 – 146.
14. Baskic, D., Vukovic, V. R., Popovic, S., Djurdjevic, P., Zaric, M., Nikolic, I., et al. (2017). Cytokine profile in chronic hepatitis C: An observation. Cytokine, 96, 185–188. https://doi.org/10.1016/j.cyto.2017.03.014 (doi.org in Bing)
15. Brancaccio, G., Coco, B., Nardi, A., Quartana, M. G., Tosti, M. E., Ferrigno, L., …, Morisco, F. (2023). Trends in chronic hepatitis B virus infection in Italy over a 10-year period: Clues from the nationwide PITER and MASTER cohorts toward elimination. International Journal of Infectious Diseases, 12 (9), 266-273.
16. Conners, E. E., Lakshmi, P., Megan, G. H., Philip, R. S., Liesr, M. H., Aaron, M. H., …, & Noele P. N. (2022). Screening and testing for hepatitis B virus infection: CDC recommendations United States. Motility and Mortality Weekly Report Recommendation, 7 (2), 1-25.
17. Damiani, M., Brand, A., Andreani, J., Mark, L., Mulder, A., Su, J., sabanjoo, J. (2024). Guideline for the prevention, diagnosis, care and treatment of people with chronic hepatitis B infection. World Journal of Gastroenterology. ISBN 978-992-4-009090-3. https://creativecommons.org/licnses/by-nc-sa/3.0 igo.
18. Dimitriadis, S., Katelani, S., Pappa, M., Fragkoulis, G.E. and Androutsakos M. (2023). The role of interleukins in HBV infection: A narrative review. Journal of Personalize Medicine. 13 (12), 10.3390/JPM13121675.
19. El-deen, R. A. A., Harfoush, R. A., Elgharabawy, M. M., Hamed, N. A. & Morsi, M. G. (2021). Levels of interleukins 10 (IL-10) and 12 (IL-12), hepatitis B and C serology, and blood cultures among acute myeloid leukemia (AML) patients in Egypt. Journal of Venom Anim Toxins Incl Tropical Disease, 17 (3), 293-299.
20. Faddy, H. M., Osiowy, C., Custer, B., Busch, M., Stramer, S. L., Adesina, O., …, & Charlewood, R. (2024). International review of blood donation nucleic acid amplification testing, International Society of Blood Transfusion, 119, 315-25.
21. Florescu, D. N., Boldeanu, M. V., Emmanuel-Serban, R., Vere, C. C., et al. (2023). Correlation of the pro-inflammatory cytokines IL-1ß, IL-6, and TNF-a, inflammatory markers, and tumor markers with the diagnosis and prognosis of colorectal cancer. Life, 13(12), 2261. https://doi.org/10.3390/life13122261 (doi.org in Bing)
22. Hoogeveen, R.C., Robidoux, M.P., Schwarz, T., Heydmann, L. & Cheney, J.A., Kvistad, D. (2019). Phenotype and function of HBV-specific T cells is determined by the targeted epitope inaddition to the stage of infection. Gut, 68 (5), 893-904. doi: 10.1136/gutjnl-2018-316644.
23. Iannacone, M. & Guidotti, L.G. (2022). Immunobiology and pathogenesis of hepatitis B virus infection. Nature Reviews Immunology, 22 (1), 19-32. Doi 10.1038/s41577-021-00549-4.
24. Karlstrom, C., Linjama, T., Edgren, G., Lauronen, J., Wikman, A. & Hoglund, P. (2019). HLA selected platelets for platelet refractory patients with HLA antibodies: A single-center experience. Transfusion,59, 945-952. doi :10.1111/trf.15108.
25. Khadr Ahmed (2020). Incidence and clinical implications of isolated hepatitis B core Antibody Serologic profile pattern among Egyptian patients with chronic hepatitis C. Egypt Academic Journal of Biological Science, Physiology and Molecular Biology, 12 (2), 169-80. https://doi.org/10.21608/eajbsc.2020.133909.
26. Li, X., Liu, X., Tian, L., et al. (2016). Cytokine-mediated immunopathogenesis of hepatitis B virus infections. Clinical Reviews in Allergy & Immunology, 50(1), 41–52. https://doi.org/10.1007/s12016-015-8490-0 (doi.org in Bing)
27. Liu, Q., Tian, Y., Li, Y., Zhang, W., Cai, W. & Liu, Y. (2020). In vivo therapeutic effects of affinity-improved-TCR Engineered T-cells on HBV-related hepatocellular carcinoma. Journal of Immunotherapy and Cancer, 8 (2), e1748. doi: 10.1136/jitc-2020-001748.
28. Mekonnen, D., Solomon, T. & Nigatu, M. (2022). Prevalence of hepatitis B virus and its predictors among volunteer blood donors in Jimma, Ethiopia: A crosssectional study. Journal of Clinical Virology Plus, 2 (4),100122.
29. Michael, X. F., Peter, S., Monique, A. & Heli, H. (2024). Biomarkers of transfusion transmitted Occult hepatitis B virus infection: Where are we and what next? Revised Journal of Medical Virology,7 (1), 1-12. https://doi.org/10.1002/rmv.2525.
30. Mohamed, Y. A. G., Doutoum, A. A., Mahamat, A. B., Doungous, D. M., Gabbad, A. A. & Osmab, R. M. (2022). Prevalence and risk factors of Hepatitis B among the population at AlgamosiLocality, Gezira State, Sudan. Health Journal, 14, 1191-1198.
31. Mohamud, A.K., Ahmed, O.A., Ali, I.A. & Dirie, N.I. (2023). Demographical, clinical, and Complication differences between vaccinated and unvaccinated hospitalized children with measles in Mogadishu Somalia: A hospital-based retrospective cohort study. Annals Medicine and Surgery, 85 (5), 1550-1558.
32. Musa B. M., Okojokwu, O. J., Makeri, M. S., Kwaifa, I. K., Ndidi, C. O.-N., & Lar, P. M. (2026). Virologic polymorphism of occult hepatitis B infection (OBI) among blood donors in Abuja. Clinical Medicine and Health Research Journal, 6(3), 1771–1783. https://www.cmhrj.com
33. Osasona, O. G., Oguntoye, O. O., Arowosaye, A. O., Abdulkareem, L. O., Adewumi, M. O., Happi, C. & Folarin, O. (2023). Patterns of hepatitis b virus immune escape and pol/rtmutations across clinical cohorts of patients with genotypes a, e and occult hepatitis B. International Journal of Health Sciences, 12, 25-29.
34. Osuji, A., Agbakaba, N.R., Ifeanyichukwu, M.O. and Tatfeng, M. (2018). Occult hepatitis B virus infection among Blood donors at two teaching hospitals in Nigeria: Implication for blood transfusion. American Journal of Infectious Diseases and Microbiology. 6 (1): 16 – 25.
35. Persson, G., Picard, C., Marin, G., Isgaard, C., Stæhr, C. S., Molinari, N., …, & Di-Cristofaro, J. (2021) Maternal HLA Ib polymorphisms in pregnancy allo-immunization. Frontier Immunology, 12, 657217. doi:10.3389/fimmu.2021.657217.
36. Ramezani, A., Banifazl, M., Mamishi, S., Sofian, M., Eslamifar, A., & Aghakhani, A. (2012). The influence of human leukocyte antigen and IL-10 gene polymorphisms on hepatitis B virus outcome. Hepatology Monthly, 12(5), 320–325. https://doi.org/10.5812/hepatmon.6094 (doi.org in Bing)
37. Ribeiro, C. R. de A., Almeida, N. A. A. de, Martinelli, K. G., Pires, M. A., Mello, C. E. B., Barros, J. J., & de Paula, V. S. (2021). Cytokine profile during occult hepatitis B virus infection in chronic hepatitis C patients. Virology Journal, 18, 15. https://doi.org/10.1186/s12985-021-01501-7 (doi.org in Bing)
38. Rindlisbacher, L., Navarro, M. N., & Becher, B. (2026). Inflame and restrain — the paradoxical roles of IL-12 and IL-23 in immunity. Nature Reviews Immunology, 26(6), 410–421. https://doi.org/10.1038/s41577-025-01079-5 (doi.org in Bing)
39. Rijkers, M., Schmidt, D., Lu, N., Kramer, C.S.M., Heidt, S., Mulder, A., (2019). Anti-HLA antibodies with complementary and synergistic interaction geometries promote classical complement activation on platelets. Haematological, 104:403–16. doi: 10.3324/ haematol.2018.201665 2.
40. Sosa-Jurado, F., Sánchez-Reza, L., Mendoza-Torres, M. Á., Meléndez-Mena, D., García y García, V. H., Guzmán-Flores, B., Enciso-Moreno, J. A., López-Ramos, J. E., Balandrán, J. C., Vallejo-Ruiz, V., Cortes-Hernández, P., Reyes-Leyva, J., & Santos-López, G. (2021). Serum Th17 and TNF-a distinguish between patients with occult hepatitis B infection, chronic hepatitis B infection and healthy individuals. European Cytokine Network, 32(1), 23–30. https://doi.org/10.1684/ecn.2021.0470 (doi.org in Bing)
41. Tuzlak, S., et al. (2021). Repositioning TH cell polarization from single cytokines to complex help. Nature Immunology, 22(12), 1210–1217. https://doi.org/10.1038/s41590-021-01021-3 (doi.org in Bing)
42. Valaydon, Z., Pellegrini, M., Thompson, A., et al. (2016). The role of tumour necrosis factor in hepatitis B infection: Jekyll and Hyde. Clinical & Translational Immunology, 5(7), e115. https://doi.org/10.1038/cti.2016.62
43. Wang, H., Luo, H., Wan, X., et al. (2020). TNF-a/IFN-? profile of HBV-specific CD4 T cells is associated with liver damage and viral clearance in chronic HBV infection. Journal of Hepatology, 72(1), 45–56. https://doi.org/10.1016/j.jhep.2019.08.030
44. Waggiallah, H. A., Abakar, M., Ali, A. H. H., Elhassan, E. D. A., Hussein, A. A., Abakar, M., Ahmed, E. D., & Waggiallah, H. A. (2023). Association of TNF-a, IFN-?, IL-6, and IL-10 with different clinical manifestations of hepatitis B infection. Italian Journal of Medicine, 17(1), Article 1627. https://doi.org/10.4081/itjm.2023.1627 (doi.org in Bing)
45. Walker, A., Schwarz, T., Brinkmann, P. J., Wisskirchen, K., Menne, C., Alizei, E. S., …, & Timm, J. (2022). Immune escape pathways from the HBV core18-27 CD8 T cell response are driven by individual HLA class I alleles. Frontier Immunology, 1045498.doi:10.3389/fimmu.1045498.
46. Wu, J. F., Wu, T. C., Chen, C. H., Ni, Y. H., Chen, H. L., Hsu, H. Y., et al. (2020). Serum levels of interleukin-10 and interleukin-12 predict early spontaneous hepatitis B virus e antigen seroconversion. Gastroenterology, 138(1), 165–172.e1. https://doi.org/10.1053/j.gastro.2009.09.016 (doi.org in Bing)
47. Xuelian, F.M., Simmonds, P., Andreani, J., Baklan, H., Webster, M., Asadi, R. (2021). Ultrasensitive PCR system for HBV DNA detection: risk stratification for occult hepatitis B virus infection in English blood donors. Journal of Medical Virology. 95: e29144.
48. Yang, G., Wan, P. & Zhang, Y. (2022). Innate immunity, inflammation, and intervention in HBV infection. Viruses, 14 (10), e2275. https:// doi.org/10.3390/V14102275.
49. Yarzabek, B., Zaitouna, A. J., Olson, E., Silva, G. N., Geng, J. & Geretz, A. (2018). Variations in HLA-b cell surface expression, half-life and extracellular antigen receptivity. Elife, 7, e34961. doi:10.7554/eLife.34961.
50. Zhang, Y., Wu, Y., Deng, M., Xu, D., Li, X. & Xu, Z. (2018). CD8(+) T-Cell Response associated evolution of hepatitis B virus core protein and disease progress. Journal of Virology ,92 (17), e02120-17. doi: 10.1128/JVI.02120-17.
51. Ziegler, S., Skibbe, K., Walker, A., Ke, X., Heinemann, F. M. & Heinold, A. (2014). Impact of sequence variation in a dominant HLA-A*02-restricted epitope in hepatitis c virus on priming and cross-reactivity of CD8+ T-cells. Journal of virology, 88(19), 11080-11090.doi: 10.1128/JVI.01590-14.
