A Review of Cytokine Detection Methods in β-Thalassemia Major Patients

Ali Alsamiri; Wan Ismahanisa Ismail; Talal Qadah

doi:10.21834/e-bpj.v10iSI35.7498

Authors

Ali Alsamiri Miqat General Hospital in Madinah, Ministry of Health, Saudi Arabia; Faculty of Health Sciences, Department of Medical Laboratory Technology, Universiti Teknologi MARA (UiTM), Malaysia
Wan Ismahanisa Ismail Faculty of Health Sciences, Department of Medical Laboratory Technology, Universiti Teknologi MARA (UiTM), Malaysia; Health Science Faculty, Universitas Pembangunan Nasional Veteran Jakarta, Jakarta 12450, Indonesia; Division of Medical Laboratory Technology, Department of Health, Faculty of Vocational Studies, Universitas Airlangga Surabaya, Indonesia
Talal Qadah Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia

DOI:

https://doi.org/10.21834/e-bpj.v10iSI35.7498

Keywords:

Beta-thalassemia major (β-TM), cytokines, ELISA, Luminex

Abstract

β-thalassemia major (β-TM) is defined by persistent inflammation and immune dysfunction, with cytokine profiling being crucial for diagnosis and research. This review evaluates methodologies used in cytokine quantification among β-TM patients. A targeted literature search revealed prominent methods such as ELISA, Luminex, flow cytometry, and qRT-PCR. Although ELISA remains the most common method, methodological discrepancies and limited cytokine panels hinder data comparability. Multiplex technologies offer improved efficiency but remain underused. Enhanced standardization and broader cytokine coverage are essential to strengthen biomarker discovery and clinical application in β-TM research. Findings suggest that researchers require unified, multiplex-capable platforms in future investigations.

References

Abdelrazek, H., Mostafa, A., & Emam, N. (2018). Pro- and anti-inflammatory cytokine patterns in children with transfusion-dependent thalassemia. Egyptian Journal of Hematology, 43(3), 107–113.

Ahmad, A. M., Alzahrani, M. A., & Khan, I. A. (2022). Serum cytokine levels in Saudi children with transfusion-dependent beta-thalassemia. Journal of Pediatric Hematology/Oncology, 44(3), 123–129.

Akcalı, A., Çeneli, S. K., Meriç, P., Nalbantsoy, A., Ozçaka, Ö., & Buduneli, N. (2019). Altered levels of inhibitory cytokines in patients with thalassemia major and gingival inflammation. Brazilian Dental Science, 22(3), 349–357. DOI: https://doi.org/10.14295/bds.2019.v22i3.1708

Alzahrani, M. A., Alghamdi, M. A., & Alotaibi, A. S. (2021). Assessment of IL-1β and IL-6 in pediatric β-TM patients in relation to ferritin and liver enzymes. Saudi Medical Journal, 42(8), 845–851.

Ansari, S. H., Ashraf, M., & Imran, M. (2020). Immunological complications in thalassemia major: Current understanding and perspectives. Journal of Blood Medicine, 11, 179–189.

Baharlou, R., Davami, M. H., Ahmadi-Vasmehjani, A., & Ebrahimi, M. (2016). Increased IL-17 and TGF-β serum levels in peripheral blood of patients with β-thalassemia major: Implication for continual transfusions’ role in T helper 17-mediated pro-inflammatory responses. Turkish Journal of Medical Sciences, 46(3), 749–755. DOI: https://doi.org/10.3906/sag-1409-57

Brbber, A. M., Fatemi, F., Ali, R. A., Ali, H. A., Al-Rufaie, M. M., Madlool, A. K., & Abbas, A. J. (2023). Correlation between serum IL-33 with iron status and zinc, copper levels in Iraqi children with β-thalassemia major. Egyptian Academic Journal of Biological Sciences C: Physiology and Molecular Biology, 15(1), 365–373. DOI: https://doi.org/10.21608/eajbsc.2023.295454

Caprari, P., Profumo, E., Massimi, S., Buttari, B., Riganò, R., Regine, V., … Sorrentino, F. (2023). Hemorheological profiles and chronic inflammation markers in transfusion-dependent and non-transfusion-dependent thalassemia. Frontiers in Molecular Biosciences, 9, 1108896. DOI: https://doi.org/10.3389/fmolb.2022.1108896

Donniacuo, A., Mauro, A., Cardamone, C., Basile, A., Manzo, P., Dimitrov, J., … Rosati, A. (2025). Comprehensive profiling of cytokines and growth factors: Pathogenic roles and clinical applications in autoimmune diseases. International Journal of Molecular Sciences, 26(18), 8921. DOI: https://doi.org/10.3390/ijms26188921

Ghoti, H., Kadir, M., & Norazmi, M. N. (2019). Inflammatory cytokines in Malaysian children with beta-thalassemia major. Malaysian Journal of Pathology, 41(2), 123–130.

Gluba-Brzózka, A., Franczyk, B., Olszewski, R., & Rysz, J. (2021). Pathomechanisms of immunological disturbances in β-thalassemia. International Journal of Molecular Sciences, 22(18), 9677. DOI: https://doi.org/10.3390/ijms22189677

Haghpanah, S., Karimi, M., & Zahedi, R. (2022). Cytokine imbalance and immune modulation in beta-thalassemia major: A cross-sectional study. Iranian Journal of Immunology, 19(1), 47–56.

Hashad, R., Hamed, N. A., El Gharabawy, M. M., El Metwally, H. A., & Morsi, M. G. (2013). Interleukins 12 and 13 levels among beta-thalassemia major patients. Eastern Mediterranean Health Journal, 19(2), 181–185. DOI: https://doi.org/10.26719/2013.19.2.181

Hassan, H. J., Alwan, M. J., & Salman, A. J. (2023). The impact of iron overload and splenectomy on IL-10 and IL-4 serum levels in β-TM patients. Iraqi Journal of Hematology, 12(1), 33–40.

Liu, C., Chu, D., Kalantar-Zadeh, K., George, J., Young, H. A., & Liu, G. (2021). Cytokines: From clinical significance to quantification. Advanced Science, 8(15), 2004433. DOI: https://doi.org/10.1002/advs.202004433

Mahmoud, A. A., El-Hamid, M. E., El-Hawwary, A. M., Awad, S. W., Abdallah, H. M., Morsi, D. S., & El-Hawy, M. A. (2022). The assessment of cytokine-dependent hematopoietic cell linker and interleukin-3 levels in children with beta-thalassemia major. Questions of Hematology/Oncology and Immunopathology in Pediatrics, 21(3), 42–46. DOI: https://doi.org/10.24287/1726-1708-2022-21-3-42-46

Mansourabadi, A. H., Mohamed Khosroshahi, L., Noorbakhsh, F., Hamidieh, A. A., & Amirzargar, A. (2023). Isolation and in vitro expansion of regulatory T cells from β-thalassemia major kids and evaluation of their plasticity. International Archives of Allergy and Immunology, 184(1), 63–75. DOI: https://doi.org/10.1159/000526835

Mokhtar, G. M., El-Ayadi, A., & El-Sayed, M. H. (2019). Cytokine imbalance in beta-thalassemia major. Pediatric Hematology and Oncology, 36(1), 50–58.

Musallam, K. M., Cappellini, M. D., & Taher, A. T. (2012). Iron overload in beta-thalassemia intermedia: An emerging concern. Current Opinion in Hematology, 19(3), 187–192. DOI: https://doi.org/10.1097/MOH.0b013e32835f5a5c

Page, M. J., McKenzie, J. E., Bossuyt, P. M., Boutron, I., Hoffmann, T. C., Mulrow, C. D., et al. (2021). The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. BMJ, 372, n71. DOI: https://doi.org/10.1136/bmj.n71

Piyajaroenkij, T., Tantiworawit, A., Khikhuntod, J., Piriyakhuntorn, P., Rattanathammethee, T., Hantrakool, S., … Thananchai, H. (2023). Alteration of monocyte subsets and their functions in thalassemia patients. International Journal of Hematology, 117(2), 188–197. DOI: https://doi.org/10.1007/s12185-022-03484-9

Shahad, R. K., & Ali, B. R. (2025). Assessment of hematological and immune parameters in patients with β-thalassemia. Romanian Journal of Medical Practice, 20(2). DOI: https://doi.org/10.37897/RJMP.2025.2.2

Shanab, A. M., El-Desouky, M. A., Kholoussi, N., El-Kamah, G., & Fahmi, A. A. (2015). Evaluation of neopterin as a prognostic factor in patients with beta-thalassemia. Archives of Hellenic Medicine, 32(1), 60–66.

Taher, A. T., Musallam, K. M., & Cappellini, M. D. (2021). Beta-thalassemia. New England Journal of Medicine, 384(8), 727–743. DOI: https://doi.org/10.1056/NEJMra2021838

Zhang, L., Bao, L. J., Hong, Z. D., Yan, M. X., Zhang, Z. H., Li, Y. M., Ye, Q., & Wang, Y. Q. (2022). Dysregulated serum cytokine production in pediatric patients with β-thalassemia major. Hemoglobin, 46(4), 191–196. DOI: https://doi.org/10.1080/03630269.2022.2070499

Zhou, Y., Liu, X., & Xu, J. (2020). Expression of cytokine-related genes in thalassemia and their association with disease severity. International Journal of Hematology, 112(4), 536–544.