Prevalence and Immune Response with Interferons to BK Polyomavirus in Chronic Kidney Disease Patients

Ibrahim MS. Hussein ^1*, Hajir A. Shareef ²

This study determined BKPyV prevalence in CKD patients, emphasizing the role of interferons in immune response and the need for vigilant monitoring.

Abstract

Background: BK polyomavirus (BKPyV) is recognized as a significant cause of renal impairment and graft failure in transplant recipients, with its reactivation posing severe complications, especially in immunocompromised individuals. Although BKPyV infection is well-documented in various populations, there is limited research on its prevalence and impact in Iraq, particularly among patients with chronic kidney disease (CKD). This study aimed to evaluate the prevalence of BKPyV in CKD patients and assess its relationship with interferon alpha and beta levels. Methods: The study included 130 CKD patients (76 males and 54 females) divided into hemodialysis (n=110) and conservative (non-dialysis) groups (n=20), along with a control group of 50 healthy blood donors. Blood samples were analyzed for BKPyV-specific antibodies (IgM and IgG) using ELISA. Interferon alpha and beta levels were also measured. Statistical analysis was conducted to assess the association between seropositivity, interferon levels, and demographic variables. Results: Among the non-dialysis CKD patients, 10% tested positive for anti-IgG, while all samples were negative for anti-IgM. In contrast, 19% of hemodialysis patients were anti-IgG positive, 14.5% were anti-IgM positive, and 8.2% were positive for both antibodies. Elevated levels of interferon alpha and beta were observed in seropositive patients compared to controls, with significant differences at P < 0.05. Male patients aged 20-29 and female patients aged 40-49 exhibited higher seropositivity rates. Conclusion: The study highlights a notable prevalence of BKPyV among CKD patients in Iraq, particularly those undergoing hemodialysis. Elevated interferon alpha and beta levels in seropositive patients suggest a significant role of these cytokines in the immune response against BKPyV infection. The findings also indicate demographic variations in seropositivity, emphasizing the need for targeted monitoring and management of BKPyV in CKD patients. Further research is needed to develop effective interventions for BKPyV-related complications in this high-risk population.

Keywords: BK Polyomavirus, Chronic Kidney Disease, Hemodialysis, Interferon Levels, Seropositivity

References

Ali, A. A., Alabden, S. S., & Zaman, N. A. (2020). Prevalence of some gram-negative bacteria and adenovirus in breast cancer patients in Kirkuk city. International Journal of Pharmaceutical Quality Assurance, 11(2), 224-227.

Allam, R., Lichtnekert, J., Moll, A., et al. (2009). Viral RNA and DNA sense common antiviral responses including type I interferons in mesangial cells. Journal of the American Society of Nephrology, 20, 1986-1996.

Ambalathingal, G. R., Francis, R. S., Smyth, M. J., Smith, C., & Khanna, R. (2017). BK polyomavirus: Clinical aspects, immune regulation, and emerging therapies. Clinical Microbiology Reviews, 30(2), 503-528.

Anders, H. J. (2007). Innate pathogen recognition in the kidney: Toll-like receptors, NOD-like receptors, and RIG-like helicases. Kidney International, 72, 1051-1056.

Bennett, S. M., Broekema, N. M., & Imperiale, M. J. (2012). BK polyomavirus: Emerging pathogen. Microbes and Infection, 14(8), 672-683.

Boukoum, H., Nahdi, I., Sahtout, W., Skiri, H., Segondy, M., & Aouni, M. (2016). BK and JC virus infections in healthy patients compared to kidney transplant recipients in Tunisia. Microbial Pathogenesis, 97, 204-208.

Chen, Y. J., Liu, X., & Tsai, B. (2019). SV40 hijacks cellular transport, membrane penetration, and disassembly machineries to promote infection. Viruses, 11(10), 917.

Egli, A., Infanti, L., Dumoulin, A., Buser, A., Samaridis, J., Stebler, C., Gosert, R., & Hirsch, H. (2009). Prevalence of polyomavirus BK and JC infection and replication in 400 healthy blood donors. Journal of Infectious Diseases, 199, 837-846.

Favi, E., Puliatti, C., Sivaprakasam, R., Ferraresso, M., Ambrogi, F., Delbue, S., & Cacciola, R. (2019). Incidence, risk factors, and outcome of BK polyomavirus infection after kidney transplantation. World Journal of Clinical Cases, 7(3), 270.

Genin, P., Vaccaro, A., & Civas, A. (2009). The role of differential expression of human interferon-alpha genes in antiviral immunity. Cytokine Growth Factor Reviews, 20, 283-295.

Hameed, H. S., Yenzeel, J. H., & Sabbah, M. A. (2023). Evaluation of the level of some interleukins in the serum of Iraqi patients with endometrial carcinoma. Iraqi Journal of Science, 64(9), 4366-4374.

Hewagama, A., Patel, D., Yarlagadda, S., et al. (2009). Stronger inflammatory/cytotoxic T-cell response in women identified by microarray analysis. Genes and Immunity, 10(5), 509-516.

Hussein, S. F., Zaman, A. N., & Shareef, A. H. (2022). Comparison between immune-chromatography (ICT) and ELISA techniques for detection of anti-HAV antibodies among patients suspected to be infected with Hepatitis A virus (HAV). Revis Bionatura, 7(2), 18.

IBM Corp. (2019). IBM SPSS Statistics for Windows. Armonk, NY: IBM Corp.

Klein, S. (2012). Immune cells have sex and so should journal articles. Endocrinology, 153(6), 2544-2550.

Klein, S., Jedlicka, A., & Pekosz, A. (2012). The Xs and Y of immune responses to viral vaccines. Lancet Infectious Diseases, 10(5), 338-349.

Knowles, W. A. (2006). Discovery and epidemiology of the human polyomaviruses BK virus (BKV) and JC virus (JCV). In Polyomaviruses and Human Diseases (pp. 19–45).

Maria, D., Caterina, C., Federico, A., Evaldo, F., Lucia, S., Marta, P., Edoardo, C., Kevin, K., Pasquale, F., Mariano, F., & Serena, D. (2024). Longitudinal study of human polyomaviruses viruria in kidney transplant recipients. Clinical and Experimental Medicine, 24(3), 1-11.

Marriott, I., & Huet-Hudson, Y. (2006). Sexual dimorphism in innate immune responses to infectious organisms. Immunology Research, 34(3), 177-192.

Mohammad, T. S., & Dawood, D. S. (2016). Detection of Polyomavirus BK and JC in kidney transplant recipients. Iraqi National Journal of Nursing Specialties, 29(2).

Najafabadi, M. M., Soleimani, M., Ahmadvand, M., Zomorrod, M. S., & Mousavi, S. A. (2020). Treatment protocols for BK virus-associated hemorrhagic cystitis after hematopoietic stem cell transplantation. American Journal of Blood Research, 10(5), 217.

Popik, W., Khatua, A. K., Fabre, N. F., Hildreth, J. E., & Alcendor, D. J. (2019). BK virus replication in the glomerular vascular unit: Implications for BK virus-associated nephropathy. Viruses, 11(7), 583.

Randhawa, P., Bohl, D., Brennan, K., Ruppert, B., Ramaswami, G., Storch, J., March, R., & Shapiro, R. (2008). Longitudinal analysis of levels of immunoglobulins against BK virus capsid proteins in kidney transplant recipients. Clinical and Vaccine Immunology, 15(10), 1564-1571.

Saade, A., Styczynski, J., & Cesaro, S. (2020). BK virus infection in allogeneic hematopoietic cell transplantation: An update on pathogenesis, immune responses, diagnosis, and treatments. Journal of Infection, 81(3), 372-382.

Sabri, S. A., & Ibraheem, S. R. (2023). Comparing the disease severity in Iraqi psoriasis patients according to some immunological and biological factors. Iraqi Journal of Science, 64(6), 2774-2785.

Schmidt, T., Adam, C., Hirsch, H. H., Janssen, M. W., Wolf, M., Dirks, J., et al. (2014). BK polyomavirus-specific cellular immune responses are age-dependent and strongly correlate with phases of virus replication. American Journal of Transplantation, 14, 1334-1345.

Sharif, A., Sharif, M. R., Aghakhani, A., Banifazl, M., Hamkar, R., Ghavami, N., Eslamifar, A., & Ramezani, A. (2015). Prevalence of BK viremia in Iranian hemodialysis and peritoneal dialysis patients. Infectious Diseases, 47, 345-348.

Sharma, R., & Zachariah, M. (2020). BK Virus nephropathy: Prevalence, impact, and management strategies. International Journal of Nephrology and Renovascular Disease, 13, 187-192.

Theofilopoulos, A. N., Baccala, R., Beutler, B., et al. (2005). Type I interferons (alpha/beta) in immunity and autoimmunity. Annual Review of Immunology, 23, 307-336.

Voskuhl, R. (2011). Sex differences in autoimmune diseases. Biology of Sex Differences, 2(1), 1-21.