Immunological Impact of Calprotectin and Interleukin-34 in Immunocompromised Patients with Chronic Cytomegalovirus Infection
DOI:
https://doi.org/10.14500/aro.12415Keywords:
Biomarker, Calprotectin, Cytomegalovirus, Immunocompromised, Interleukin-34, SulaimaniAbstract
Cytomegalovirus (CMV) causes the most prevalent and severe opportunistic infection in immunocompromised patients following solid organ or hematopoietic stem cell transplantation, with the highest morbidity and mortality rates among herpesviruses. The study objective was to compare and determine the CMV chronic infection and related hematological and immunological markers in immunodeficient and immunocompetent participants. A prospective case–control study among 85 participants was designed to measure CMV-immunoglobulin G (IgG) and to evaluate interleukin-34 and serum calprotectin as biomarkers; total leukocyte, granulocyte, lymphocyte, and platelet counts were also measured following blood collection. A high CMV IgG positivity was observed across all groups in this investigation, indicating widespread chronic infection. CMV IgG, interleukin-34 (IL-34), and calprotectin levels did not differ significantly between immunocompetent and immunocompromised individuals. There was no significant association between CMV IgG and IL-34 or serum calprotectin. Furthermore, IL-34 showed a significantly higher mean in males compared to females (p = 0.002). An exploratory observation was that IL-34 had a moderate positive correlation with serum calprotectin (ρ = 0.609, 95% confidence interval: 0.450–0.731, p < 0.001) across all study participants. The study findings call for more research to elucidate the clinical roles of calprotectin and IL-34 in immunocompromised patients.
Downloads
References
Abdulqader Naqid, I., Hassan Yousif, S., Rasheed Hussein, N., and Naqid, I.A., 2019. Serological study of IgG and IgM antibodies to cytomegalovirus and toxoplasma infections in pregnant women in Zakho City, Kurdistan region, Iraq. Women’s Health Bulletin, 6(4), p.9.
Al-Alousy, B.M., Hasan Abdul-Razak, S., Al-Ajeeli, K.S., and Al-Jashamy, K.A., 2011. Renal data from the Arab world anti-HCMV IgG positivity rate among renal transplant recipients in Baghdad. Saudi Journal of Kidney Diseases and Transplantation, 22(6), pp.1269-1274.
Aljumaili, Z.K.M., Alsamarai, A.M., and Najem, W.S., 2014. Cytomegalovirus seroprevalence in women with bad obstetric history in Kirkuk, Iraq. Journal of Infection and Public Health, 7(4), pp.277-288.
Al-Zubaidi, M.A.K., Hosseini, S.M., Al-Roudhan, M.A.N., and Al-Harmooshee, M.B.H., 2025. Serological epidemiology analysis of Cytomegalovirus infection in pregnant women in Diwaniyah, Iraq. Iranian Journal of Microbiology, 17(1), pp.128-136.
Atabani, S.F., Smith, C., Atkinson, C., Aldridge, R.W., Rodriguez-Perálvarez, M., Rolando, N., Harber, M., Jones, G., O’Riordan, A., Burroughs, A.K., Thorburn, D., O’Beirne, J., Milne, R.S.B., Emery, V.C., and Griffiths, P.D., 2012. Cytomegalovirus replication kinetics in solid organ transplant recipients managed by preemptive therapy. American Journal of Transplantation, 12(9), pp.2457-2464.
Baghdadi, M., Ishikawa, K., Nakanishi, S., Murata, T., Umeyama, Y., Kobayashi, T., Kameda, Y., Endo, H., Wada, H., Bogen, B., Yamamoto, S., Yamaguchi, K., Kasahara, I., Iwasaki, H., Takahata, M., Ibata, M., Takahashi, S., Goto, H., Teshima, T., and Seino, K.I., 2019. A role for IL-34 in osteolytic disease of multiple myeloma. Blood Advances, 3(4), pp.541-551.
Bayrakci, N., Ozkan, G., Kara, S.P., Yilmaz, A., and Guzel, S., 2022. Serum calprotectin level as an inflammatory marker in newly diagnosed hypertensive patients. International Journal of Hypertension, 2022, p.6912502.
Cai, H., Jin, S., Lin, J., Yu, L., Xu, J., Qian, P., and Chen, W., 2022. IL-34 was high in serum of women with polycystic ovary syndrome and may function as potential diagnostic biomarker and therapeutic target. Journal of Obstetrics and Gynaecology Research, 48(4), pp.973-979.
Castillo, N., García-Cadenas, I., Barba, P., Canals, C., Díaz-Heredia, C., Martino, R., Ferrà, C., Badell, I., Elorza, I., Sierra, J., Valcárcel, D., and Querol, S., 2017. Early and long-term impaired T lymphocyte immune reconstitution after cord blood transplantation with antithymocyte globulin. Biology of Blood and Marrow Transplantation, 23(3), pp.491-497.
Chaemsupaphan, T., Limsrivilai, J., Thongdee, C., Sudcharoen, A., Pongpaibul, A., Pausawasdi, N., and Charatcharoenwitthaya, P., 2020. Patient characteristics, clinical manifestations, prognosis, and factors associated with gastrointestinal cytomegalovirus infection in immunocompetent patients. BMC Gastroenterology, 20(1), p.22.
Chen, M.X., Chen, Y., Fu, R., Wang, J.Y., Liu, S.Y., and Shen, T.B., 2025. Cytomegalovirus infection initiates inflammatory bowel disease by activating a positive MyD88/NF-κB feedback loop in allogeneic skin transplantation mice. Virology Journal, 22(1), p.101.
Colombo, R., Gallipoli, P., and Castelli, R., 2014. Thrombosis and hemostatic abnormalities in hematological malignancies. Clinical Lymphoma Myeloma and Leukemia, 14, pp.441-450.
Dalvand, Z., Vafaeian, A., Balighi, K., Mahmoudi, H., Dasdar, S., Kianfar, N., Shalviri, A., Razavi, Z., and Daneshpazhooh, M., 2025. Impact of rituximab on IgG and IgM levels in patients with autoimmune bullous diseases: A cohort study. Springer Nature Link, 317(1), p.354.
Fernández, S., Grafia, I., Peyrony, O., Canet, E., Vigneron, C., Monet, C., Issa, N., Decavele, M., Moreau, A.S., Lautrette, A., Lacave, G., Morel, G., Cadoz, C., Argaud, L., Statlender, L., Azem, K., Quenot, J.P., Lesieur, O., Fernández, J., Farrero, M., Marcos, M.Á., Lemiale, V., Castro, P., and Azoulay, É., 2024. Clinical characteristics and outcomes of immunocompromised critically ill patients with cytomegalovirus end-organ disease: A multicenter retrospective cohort study. Critical Care, 28(1), p.243.
Franzè, E., Stolfi, C., Monteleone, G., Troncone, E., and Scarozza, P., 2020. Role of interleukin-34 in cancer. Cancers (Basel), 12(1), p.252.
Freuchet, A., Salama, A., Remy, S., Guillonneau, C., and Anegon, I., 2021. IL-34 and CSF-1, deciphering similarities and differences at steady state and in diseases. Journal of Leukocyte Biology, 110, pp.771-796.
Griffiths, P., and Reeves, M., 2021. Pathogenesis of human cytomegalovirus in the immunocompromised host. Nature Reviews Microbiology, 19(12), pp.759-773.
Hurst, F.P., Belur, P., Nee, R., Agodoa, L.Y., Patel, P., Abbott, K.C., and Jindal, R.M., 2011. Poor outcomes associated with neutropenia after kidney transplantation: Analysis of United States renal data system. Transplantation, 92(1), pp.36-40.
Imhann, F., Vich Vila, A., Bonder, M.J., Fu, J., Gevers, DI., Visschedijk, M.C., Spekhorst, L.M., Alberts, R., Franke, L., Van Dullemen, H.M., Ter Steege, R.W.F., Huttenhower, C., DIjkstra, G., Xavier, R.J., Festen, E.A.M., Wijmenga, C., Zhernakova, A., and Weersma, R.K., 2018. Interplay of host genetics and gut microbiota underlying the onset and clinical presentation of inflammatory bowel disease. Gut, 67(1), pp.108-119.
Kanki, T., Kuwabara, T., Morinaga, J., Fukami, H., Umemoto, S., Fujimoto, D., Mizumoto, T., Hayata, M., Kakizoe, Y., Izumi, Y., Tajiri, S., Tajiri, T., Kitamura, K., and Mukoyama, M., 2020. The predictive role of serum calprotectin on mortality in hemodialysis patients with high phosphoremia. BMC Nephrology, 21(1), pp.1-10.
Kew, V.G., Yuan, J., Meier, J., and Reeves, M.B., 2014. Mitogen and stress activated kinases act co-operatively with CREB during the induction of human cytomegalovirus immediate-early gene expression from latency. PLoS Pathogens, 10(6), p.e1004195.
Kopi, T.A., Shahrokh, S., Mirzaei, A., Aghdaei, H.A., and Kadijani, A.A., 2019. The role of serum calprotectin as a novel biomarker in inflammatory bowel diseases: A review study. Gastroenterology and Hepatology from Bed to Bench, 12(3), p.183.
Kuhara, A., Okumura, M., Kimata, T., Tanizawa, Y., Takano, R., Kimura, K.D., Inada, H., Matsumoto, K., and Mori, I., 2008. Temperature sensing by an olfactory neuron in a circuit controlling behavior of C. Elegans. Science, 320(5877), pp.803-807.
Lee, S., Kang, S., Joo, Y.S., Lee, C., Nam, K.H., Yun, H.R., Park, J.T., Chang, T.I., Yoo, T.H., Kim, S.W., Oh, K.H., Kim, Y.H., Park, S.K., Kang, S.W., Choi, K.H., Ahn, C., and Han, S.H., 2021. Smoking, smoking cessation, and progression of chronic kidney disease: Results from KNOW-CKD study. Nicotine and Tobacco Research, 23(1), pp.92-98.
Lee, S.Y., Han, K., Kwon, H.S., Koh, E.S., and Chung, S., 2025. Fecal calprotectin as a prognostic biomarker for mortality and renal outcomes in chronic kidney disease. Biomolecules, 15(4), p.557.
Liu, M.H., Guo, X., Sun, M.L., Li, J.L., Liu, S.H., Chen, Y.Z., Wang, D.Y., Wang, L., Li, Y.Z., Yao, J., Li, Y., and Pan, Y.Q., 2024. Rapid detection of human cytomegalovirus by multienzyme isothermal rapid amplification and lateral flow dipsticks. Frontiers in Cellular and Infection Microbiology, 14, p.1430302.
Monteleone, G., Franzè, E., Troncone, E., Maresca, C., and Marafini, I., 2022. Interleukin-34 mediates cross-talk between stromal cells and immune cells in the gut. Frontiers in Immunology, 13, p.873332.
Ritz, E., Zeier, M., and Orth, S.R., 2000. Smoking - a renal risk factor. Nephron, 86(1), pp.12-26.
San Segundo, D., Ruiz, P., Irure, J., Arias-Loste, M.T., Cuadrado, A., Puente, A., Casafont, F., López-Hoyos, M., Crespo, J., and Fábrega, E., 2016. Serum levels of interleukin-34 during acute rejection in liver transplantation. Transplantation Proceedings, 48(9), pp.2977-2979.
Shang, J., Xu, Y., Pu, S., Sun, X., and Gao, X., 2023. Role of IL-34 and its receptors in inflammatory diseases. Cytokine, 171, p.156348. Sinclair, J., 2008. Human cytomegalovirus: Latency and reactivation in the myeloid lineage. Journal of Clinical Virology, 41(3), pp.180-185.
Toma, L., Dodot, M., Zgura, A., Bacalbasa, N., Silaghi, A., Simu, R., Isac, T., and Mercan-Stanciu, A., 2022. Calprotectin in viral systemic infections-COVID-19 versus hepatitis C virus. Clinical and Experimental Medicine, 22(2), pp.311-317.
Vasiljevic, T., Jankovic, M., Tomic, A., Bakrac, I., Radenovic, S., Miljanovic, D., Knezevic, A., Jovanovic, T., Djunic, I., and Todorovic-Balint, M., 2024. Significance of cytomegalovirus gB genotypes in adult patients undergoing hematopoietic stem cell transplantation: Insights from a single-centre investigation. Pharmaceuticals (Basel), 17(4), p.428.
Weber, D., Jenq, R.R., Peled, J.U., Taur, Y., Hiergeist, A., Koestler, J., Dettmer, K., Weber, M., Wolff, D., Hahn, J., Pamer, E.G., Herr, W., Gessner, A., Oefner, P.J., Van Den Brink, M.R.M., and Holler, E., 2017. Microbiota disruption induced by early use of broad-spectrum antibiotics is an independent risk factor of outcome after allogeneic stem cell transplantation. Biology of Blood and Marrow Transplantation, 23(5), pp.845-852.
Xing, C., and Lo, E.H., 2017. Help-me signaling: Non-cell autonomous mechanisms of neuroprotection and neurorecovery. Progress in Neurobiology, 152, p.181-199.
Yu, G., Bing, Y., Zhu, S., Li, W., Xia, L., Li, Y., and Liu, Z., 2015. Activation of the interleukin-34 inflammatory pathway in response to influenza a virus infection. The American Journal of the Medical Sciences, 349(2), pp.145-150.
Yu, M., Liu, M., Zhang, W., and Ming, Y., 2018. Pharmacokinetics, pharmacodynamics and pharmacogenetics of tacrolimus in kidney transplantation. Current Drug Metabolism, 19(6), pp.513-522.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2026 Honya Hamasalim, Muhammed Babakir-Mina

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
Authors who choose to publish their work with Aro agree to the following terms:
-
Authors retain the copyright to their work and grant the journal the right of first publication. The work is simultaneously licensed under a Creative Commons Attribution License [CC BY-NC-SA 4.0]. This license allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
-
Authors have the freedom to enter into separate agreements for the non-exclusive distribution of the journal's published version of the work. This includes options such as posting it to an institutional repository or publishing it in a book, as long as proper acknowledgement is given to its initial publication in this journal.
-
Authors are encouraged to share and post their work online, including in institutional repositories or on their personal websites, both prior to and during the submission process. This practice can lead to productive exchanges and increase the visibility and citation of the published work.
By agreeing to these terms, authors acknowledge the importance of open access and the benefits it brings to the scholarly community.
Accepted 2026-01-13
Published 2026-04-03







ARO Journal is a scientific, peer-reviewed, periodical, and diamond OAJ that has no APC or ASC.